Metabolic indicators of myocardial ischemia in man.

Myocardial metabolism had been studied in 54 patients with continuous sampling of arterial (A) and coronary sinus (CS) blood during 8- to 10-min periods of control in sinus rhythm, rapid atrial pacing and recovery. The results showed that 17 subjects were normal or had insignificant coronary artery disease (CAD; nonischemic group = NI); 37 patients had significant CAD (ischemic group = 1) and developed clinical, hemodynamic, and electrocardographic evidence of myocardial ischemia during pacing, characterized by angina, elevated left ventricular end-diastolic pressure, and depressed ST segments. During pacing-induced ischemia the following metabolic abnormalities were detected: (1) myocardial anaerobiosis indicated by lactate % uptake ((A-CS)/AS X 100) of -17.2 +/- 5.0% (mean +/- SE); (2) myocardial loss of K+ suggested by an A-CS difference of -0.25 +/- 0.08 mEq/liter (N=18); (3) small but significant loss of inorganic phosphorus (Pi) of -1.0 +/- 1.4% (N=18); and (4) elevation of CS blood creatine phosphokinase activity (N=5). These metabolic abnormalities were temporally related to the other manifestations of myocardial ischemia and were not seen in the NI; Lactate production and Pi loss occurred in 75 and 55% of the IG, respectively, suggesting that accelerated anaerobic glycolysis was the best indicator of myocardial ischemia in man. K+ loss was an unreliable index in this experimental situation, since tachycardia alone caused significant K+ egress from the heart. Lactate production and K+ loss were reduced by nitroglycerin, which abolished angina and improved hemodynamics and electrocardiographic manifestations. That these metabolic abnormalities were not observed in all 1 patients may have been related to methodology, the random distribution of CAD, and the fact that the chemical composition of the CS blood reflects the metabolic balance of both well oxygenated and ischemic areas of the myocardium.


Hemodynamic and metabolic responses to pacing in patients with chest pain and normal coronary arteriograms.

Hemodynamic and metabolic responses to pacing from either the coronary sinus or right atrium were evaluated in 41 patients with chest pain and normal coronary arteriograms. A group of patients (group II) with angina, lactate production, or significant ST segment depression had a significantly higher mean pulmonary capillary pressure on peak pacing or angina than did a group of patients considered to have a normal pacing response (group I). In 6 of 9 group II patients, the left ventricular end-diastolic pressure either rose abnormally with pacing or was greater than 14 mm Hg immediately after pacing and resembled that of a group of patients with coronary artery disease; Patients with a prolapsing mitral valve (group III) also had a significantly higher pulmonary capillary pressure on peak pacing as compared to those of group I, although abnormal left ventricular pressure responses occurred in only 2 of 9 of these patients. The stroke index was significantly lower in group III on peak pacing while group II was no different from group I. Lactate production occurred in 6 of 9 group II patients. However, only 1 of 6 patients with a prolapsing mitral valve who were studied for lactate production was found to produce lactate, suggesting a different mechanism for their pain.


Lipid droplets in the heart interstitium: concentration and distribution.

A morphological study of the sudanophilic lipids in dog and human hearts was carried out. The hearts of 5 mongrel dogs and 20 auricular appendices of human patients were utilized. The dog hearts were fixed in situ by perfusion with 2% glutaraldehyde, and the human tissue was fixed by immersion. For the ultrastructural study, some blocks of every portion of the specimen were postfixed in osmium and embedded in Epon. The topographical and quantitative study was done on frozen 20-mu sections of tissue stained with Sudan IV in propylene glycol and counterstained with hematein (Geigy). The results indicate that a significant quantity of visible triglycerides is extracellular and located in the interstitial spaces of the heart. The dimensions of these lipid droplets vary from 0.5 mu to more than 20 mu. The highest concentration was found in the epicardial region of the left ventricle, but a significant amount was found in the endocardium and in the middle portion of the myocardium. These observations indicate that a sizable portion of the heart interstitium is occupied by free droplets of triglycerides. This substrate pool is probably mobile and readily available as a source of energy.


Comparison of changes in myocardial balances of lactate, glucose potassium, and inorganic phosphate during pacing-induced angina.

During an atrial pacing test, a correlative study in myocardial lactate, glucose, potassium, and inorganic phosphate balances was done in 34 patients with clinical evidence of ischemic heart disease. Electrocardiogram was continuously monitored while left ventricular end-diastolic pressure (LVEDP) was measured before and immediately after pacing. Coronary angiograms performed after the pacing test revealed atherosclerotic narrowings in all patients. During pacing, 16 patients developed anginal pain, and their LVEDP increased significantly. The other 18 patients had no angina and no significant change in LVEDP. In these 18 patients, there were no significant changes throughout the pacing study in myocardial balances of lactate, glucose, potassium, and inorganic phosphate. In contrast, the 16 patients with induced angina during pacing showed a significant myocardial production of lactate and a loss of potassium. Myocardial inorganic phosphate loss was not statistically significant. There was no significant change in myocardial glucose extraction during angina, although a slight increase was observed during the 1st min afer pacingmthere was no correlation between the arterial concentration and the myocardial extraction of these substances. N stoichiometric relationship was found between glucose and lactate or between potassium and inorganic phospahte balance; Myocardial extraction and production of lactate correlated best with inorganic phosphate uptake and loss. In the preset study, lactate was a more reliable metabolic indicator of myocardial ischemia than potassium and inorganic phosphate, although these last two substances may be helpful in acheiving a greater accuracy for biochemical diagnosis of ischemia. Myocardial glucose balance was of no value as a metabolic indicator of ischemia in this pacing study.


Myocardial cell electrolytes and water during acute ischemia.

This study was intended to define the early early electrolyte and water abnormalities of ischemic myocardium in the intact anesthetized dog. We have defined the appropriate circumstances for using 52Cr-ethyelendiamineletraacetate as an extracellular marker during ischemia and have discerned no change in this space at a time when tissue water increments were observed, by 15 min of ischemia. Calculated on the basis of cell dry weight, the cell sodium increment exceeded potassium loss in this early period of ischemia. This is consistent with the view that interference with energy metabolism reduces the pumping of sodium from the cell. The enhanced entry of sodium is associated with a gain of water, initiating events that effect irreversibility.


Regional myocardial metabolism during subtotal and total coronary artery occlusion.

Regional myocardial metabolism was examined by means of coronary venous sampling in dogs having acute nonsimultaneous occlusions of the left anterior descending (LAD) and circumflex (CIRC) coronary arteries. Regional coronary venous metabolic sampling was not found to separate ischemic from nonischemic myocardium in LAD occlusion and did so imperfectly in isolated CIRC occlusion. Myocardial metabolic consequences of subtotal and total coronary artery occlusion were compared in dogs during LAD and CIRC occlusion and in human subjects with subtotal and total anterior coronary artery occlusion. In spite of ECG evidence of greater myocardial ischemia during total coronary artery occlusion in the dog, transmyocardial metabolic changes were more consistent during subtotal occlusion. Human subjects stressed during cardiac catheterization exhibited a similar apparent paradox. This suggests variable coronary venous washout from ischemic myocardium during total coronary artery occlusion and, in humans, may also reflect the presence of scar tissue. Caution is advised when interpreting myocardial metabolic information in the presence of total coronary artery occlusion, since underestimation of the extent of myocardial ischemia is more likely than with an occlusion of lesser degree.


Effects of prolonged coronary hypotension on myocardial substrate utilization.

Myocardial substrate utilization was investigated following experimental coronary hypotension in isolated in vitro perfused dog hearts. Control observations were made at the beginning and at the end of the experiments with afterload of 100 mm Hg. Between the two controls, the afterload was lowered to 50 mm Hg and kept at that level for 4 hours. The observations during the hypotensive period were compared to the two controls. Lactate uptake and the percentage contribution of the lactate to myocardial CO2 production were diminished during the hypotensive period. Myocardial free fatty acid (FFA) uptake and oxidation did not change significantly. Glucose uptake and myocardial respiratory quotient (RQ) were decreased. Thus, prolonged coronary hypotension caused a relative preference of FFA oxidation and diminished lactate and glucose uptake by the myocardium. It is of interest to note that these changes in substrate utilization were quite different from those observed during experimentally produced hemorrhagic hypotension or endotoxic shock.


Distribution of glycogen and lipids in the ischemic canine left ventricle: biochemical and light and electron microscopic correlates.

Transmural gradients in the contents of glycogen triglycerides, and phospholipids were studied in the dog left ventricle with and without 4 hours of left circumflex artery ligation. In control dogs (patent circumflex), an increasing outer to inner glycogen gradient was observed. After 4 hours of ischemia, subepicardial glycogen content was similar to control values, but midventricular and subendocardial stores were nearly depleted, thus indicating a reversal of the control gradient. These changes were seen biochemically as well as by light and electron microscopic techniques. In the present studies, conclusive evidence for a transmural gradient in tissue triglyceride content was not obtained in either control or ligated dogs. However, an approximate three-fold increase in midventricular and subendocardial triglycerides was observed in ischemic hearts. Regional contents of total tissue phospholipids appeared to be similar across the left ventricular wall in both normal and ischemic left ventricles.


Effects of coronary artery ligation and release and perfusion with glucose on cardiac energy metabolism in dogs.

Adenosine triphosphate (ATP), glycogen, and inorganic phosphorus (Pi) were assayed in myocardial tissues obtained from beating dog hearts subjected to the following procedures: Group 1. Ligation of anterior descending coronary artery(AD) for 60 min. Group 2. Perfusion of the AD with 20 mM glucose in Ringer's solution containing 1 mU regular insluin/ml, for 60 min. Group 3. Ligation of the AD for 60 min, followed by release of the ligature with re-establishment of blood flow for 30 min. Group 4. Perfusion of the AD with 20 mM glucose in Ringer's solution containing 1 mU/ml regular insulin for 60 min, followed by re-establishment of blood flow for 30 min. Samples from normal myocardium (N zone) and from the area supplied by the AD (I zone) were simultaneously obtained and the level of metabolites compared. In all four groups, ATP was significantly lower in I than N zone. However, ATP values were lower in N zone in group 1 as compared with the other groups (p less than 0.05) and higher in I zone in group 3 versus groups 1 and 2 (p less than 0.05). Glycogen was lower in I than N zones to a similar degree in all the groups. However, it was higher in the I zone in group 3 than in group 1 (p less than 0.05). Pi was significantly higher in I zone versus N zone only in group 1 (p less than 0.05). These data suggest that, the the beating dog heart, ATP and glycogen preservation in a myocardial segment rendered ischemic for 1 hour is best achieved by re-establishing circulation. Glucose infusion into the ischemic segment did not contribute significantly to the ATP stores in that segment but may have exerted a protective effect on the nonischemic zones, possibly by providing a high glucose level in the circulating blood. This protection was equally well achieved by release of the ligature with or without prior glucose infusion. The increase in Pi in the ischemic zone in the dogs with coronary ligation only is probably related to accumulation of the ion under ischemic and hypoxic conditions.


Ischemic damage and metabolism during elective cardiac arrest.

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 min. Various methods of arrest were studied, either singly or in combination and with or without coronary perfusion. The functional recovery of the heart following the termination of arrest was found to be related to the concentration of ATP and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations were dependent upon the method used to induce arrest. Normothermic ischemic arrest led to a marked reduction in high energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium, induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recoveries. The energy status and recovery associated with ischemic arrest could be improved by combining the ischemia with hypothermia or potassium arrest. The latter, while increasing recovery significantly, still failed to afford complete protection to the myocardium. Potassium chloride gave greater protection than potassium citrate. When topical hypothermia was combined with ischemia, a time and temperature relationship was demonstrated but effective protection could only be obtained with severe topical hypothermia over a relatively short time period. The results stress the importance of maintaining high energy phosphates during arrest, and this requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.


Effect of combination of stresses on myocardial metabolism.

The effect of hypoxia, exercise, and thermal stress on myocardial metabolism have been widely investigated, but little attention has been paid to studying the effects of a combination of these stress. The influence of hypoxia as modified by physical exertion (swimming) and cold stress was therefore studied. The parameters investigated included myocardial glycogen and noradrenaline, serum free fatty acid, adrenal ascorbic acid, and adrenal weight. It was observed that maximal stress was produced when hypoxia was combined with physical exertion. No suppression of cold-induced lipolysis by hypoxia was observed, in contrast to previously reported observations. Maximal depletion of cardiac blycogen and cardiac noradrenaline was noted in hypoxic exercise. Adrenal overactivity was not found to be related to any particular stress but was seen to be proportional to the severity of the stress applied.


Effect of substrate on enzyme release after coronary artery ligation in isolated rat heart.

In the present work, we tested the hypothesis that the development of myocardial infarction in the isolated perfused working rat hearts could be influenced by the nature of the substrate reaching the infarction zone. We measured cardiac output and rates of release of lactate dehydrogenase (LDH) after coronary artery ligation in hearts perfused with different substrates: glucose; palmitate, oleate, linoleate bound to albumin; palmitate-albumin plus glucose and/or insulin. Cardiac ouptut after ligation was lowest with palmitate and highest with glucose. LDH release was 5-10 times greater with FFA than with glucose, but was significantly reduced by the addition of glucose or insulin to the palmitate-albumin solution. Our results argue for an important role for substrate effects on the metabolic outocme of experimental myocardial infarction.


Regional myocardial metabolism following acute coronary artery occlusion.

Regional measurements of the consequences of coronary artery occlusions indicate myocardial derangements in both the coronary occluded and nonoccluded myocardium. The proximal left anterior descending coronary artery (LAD) was acutely occluded in 34 closed-chest anesthetized dogs through inflation of an intracoronary balloon. Temporary seperation of venous compartments was achieved by means of a balloon catheter placed within the great cardiac vein, and simultaneous blood sampling from both occluded and nonoccluded segments was carried out. Acute coronary occlusion resulted in early cardiac dysfunction which persisted during the subsequent 3 hours of LAD occlusion. Oxygen extraction increased 6-8% in both occluded and nonoccluded zones. Lactate extraction in the nonoccluded segment decreased significantly from 34.4 to 23.7% (P less than 0.05). In the occluded zone, lactate extraction dropped from 35.0 to 7.8% (P less than 0.05). Of the 34 dogs studied, 17 exhibited lactate production in the occluded segment, while 7 dogs also had lactate production in the nonoccluded region. Significant postocclusion myocardial potassium efflux was noted in both zones.


Assessment of myocardial free fatty acid metabolism in humans during heparin infusion.

Free fatty acids (FFA) have been shown to be a major myocardial substrates during the postabsorptive state in humans. In order to document the utilization of these substrates by the heart while heparin was infused, the following study was designed. During heparin infusion, total and individual FFA were measured in arterial and coronary sinus plasma during the postabsorptive state in 13 patients with coronary artery disease and in 4 patients with no evidence of cardiac disease. Oleic-1-14C acid bound to albumin was infused at a constant rate for at least 7 min into the left coronary artery. Left coronary blood flow was determined in all patients. It was assumed the oleic-1-14C acid behaves like endogenous FFA. Arterial FFA concentration was high (mean and SEM: 1 +/- 0.21 mumoles/ml) and varied by less than 10% during the course of the study in 14 of the 17 patients. Oleic acid constituted 44% of all arterial FFA. The relative concentrations of the various individual FFA were similar in arterial and coronary sinus plasma. The average FFA extraction was 19.9 +/- 2.1%. In contrast, the oleic-1-14C acid extraction was relatively more steady during the infusion, and the mean extraction of this tracer was 36.0 +/- 2.1%. Myocardial uptake for the entire group was 52.3 +/- 6.3 mumoles/min. Although a definite plateau for 14CO2 release from oleic-1-14C acid oxidation was not obtained, at least 31.8 +/- 4.3% of the removed FFA was oxidized, representing 49.3 +/- 6.4% of myocardial oxygen consumption. The failure of oleic-1-14C acid oxidation to reach a steady state was not due to delay in the myocardial CO2 pool, since 14CO2 release from infused NaH 14CO3 and lactate-1-14C in 11 other subjects revealed that in equilibrium was obtained within 5 min. These findings indicate that the generation of 14CO2 from oleic-1-14C acid oxidation is relatively slow, and the uptake of labeled FFA is partly matched by release of unlabeled FFA, suggesting that the human heart has important lipid pools.


Myocardial enzyme release from ischemic isolated perfused working rat heart.

Isolated working rat hearts were made ischemic for 5, 10, and 30 minutes respectively. After the ischemic period, all hearts were perfused in a retrograde nonworking way for 30 minutes. During the 5 first minutes of ischemia, there was a marked fall of cardiac output and coronary flow. A significant release of GOT was seen and this was more marked after longer periods of ischemia. Addition of adrenaline to the perfusate increased the enzyme release. Pacing at 400/minute, high preload, high afterload, acidosis, or alkalosis did not alter enzyme release. Glycogen, ATP and CrP levels were depressed at the end of the ischemic period, but were seen to be rising again during the retrograde perfusion. This study indicates that myocardial tissue may release enzymes without being irreversibly damaged.


Effect of a thrombolytic agent (urokinase) on necrosis after acute myocardial infarction.

Using a two-compartment model with continuous input function, the rate and extent of myocardial damage were calculated from plasma enzyme levels measured in patients suffering from acute myocardial infarction (AMI). Results were compared for four different enzymes. As regards the course of necrosis, two different hypotheses were tested and it was shown that the necrotic process has to be considered as a mulitplicative process rather than as a sudden disintigration of cells due to anoxia. Comparison of results obtained in a group of 5 patients treated with urokianse and in an untreated control group of 10 patients showed that the necrotic phase as defined by the enzyme release from the infarcted area was significantly shortened.


An improved animal model for studying the effect of drugs on myocardial metabolism during ischemia.

An improved dog model to study the effect of drugs on myocardial metabolism during ischemia is described. A reproducible degree of ischemia could be obtained by partial occlusion of the anterior descending branch of the left coronary artery (LAD), using an inflatable cuff with a micrometer. The possibility of inducing the stenosis twice in the same animal has the advantage that the animal can be used as its own control. The reproducibility of the degree of ischemia was demonstrated by the nonsignificant differences in local venous lactate, inorganic phosphate, and glucose concentrations after the first and second stenosis. The mean pressure difference over the stenosis was used to express the degree of coronary artery narrowing. In this model, one does not have to rely on the collateral circulation in collecting local venous blood. Moreover, it is very likely that this blood is obtained from the most pronounced ischemic area, which was localized with radioactive microspheres. At this degree of stenosis, left ventricular function was not affected too much, as was demonstrated by the slight changes in dP/dt max, and systolic and diastolic aortic pressure after induction of the stenosis. The usefulness of our model to evaluate the activity of drugs is demonstrated by the effect of fentanyl, a potent morphine-like analgesic, on the poststenotic local venous lactate and inorganic phosphate concentrations.


Role of adenine nucleotide translocase in metabolic change caused by ischemia.

Inhibition of adenine nucleotide translocase by elevated levels of long chain acyl-CoA esters has been shown to occur during the onset of ischemia in experiments conducted on dogs. Other findings indicate that, as a consequence of translocase inhibition, the production of mitochondrial creatine phosphate was abolished and, in this manner, respiration was slowed to state 4 or an ischemic-like condition. A variety of biochemical, hemodynamic, and ultrastructural evidence further suggest that this inhibition of adenine nucleotide transport in and out of the heart mitochondria may be the initial and key disturbance which "triggers" the more drastic metabolic changes known to occur as the degree of ischemia becomes more severe. The mitochondrial "damage" caused by long chain acyl-CoA ester inhibition of adenine nucleotide translocase appears to be reversible by carnitine.


Lipid composition of cardiac lymph.

Cardiac lymph was obtained from fasting dogs by cannulating the efferent collecting trunks and the interventricular (subepicardial) trunk. The total lipid content of the lymph was 450 mg/100 ml and consisted of 16-20% cholesterol, 30-33% triglycerides, 41% phospholipids, 2% free fatty acids, and 7-8% fatty acids esterified with cholesterol. The lipid composition of the lymph obtained from the two collecting sites was identical. We can demonstrate that the loss of total fatty acids by the myocardium due to the drainage of the interstitial fluid into the lymph represents only 2-8% of the fatty acids used. With the exception of triglycerides, the concentration of all the lipids was higher in the arterial plasma than in the lymph. The concentration of triglycerides in the lymph suggests that triglycerides are contributed from endogenous sources.


Hypoxia-induced prostaglandin release from rabbit heart.

Rabbit hearts were perfused at a pressure of 60 cm H2O with 37 degrees C Tyrode solution aerated with 5% CO2 in O2. The effluent from the heart was collected in four consecutive 10-min periods. The samples were analyzed for prostaglandins of the E series (PGE), using thin layer chromatography for identification and assay on the superfused rat stomach strip for quantitative estimation. Three different series of experiments were performed, the hearts in each series during the second effluent collection period being perfused under conditions of either hypoxia (Tyrode solution aerated with 5% O2 and 5% CO2 in N2), absence of glucose in the Tyrode solution, or hypotension/low perfusion flow (perfusion pressure lowered to 30cm H2O). In the series where glucose was omitted or hypotension/low perfusion flow was induced during the second effluent collection period, the outflow of PGE decreased exponentially throughout the four periods. In the series where hypoxia was maintained during the second effluent collection period, a marked increase in the outflow of PGE was noted after the end of hypoxia. Prostaglandins of the E series are powerful vasodilators, and the PG released may, by inducing coronary vasodilation, counteract the hypoxia. However, it has been shown that, in human plasma, conversion of arachidonic acid to PGE is parallelled by platelet aggregation. Therefore, if PG synthesis is also stimulated by hypoxia in man, myocardial ischemia must be considered as a possible mechanism for platelet aggregation and subsequent coronary thrombosis.


Influence of the adrenal medulla on cardiac rhythm disturbances following acute coronary artery occlusions.

The present study was designed to examine the relationship between epinephrine secreted from the adrenal medulla and acute occlusion of the left anterior descending (LAD) coronary artery in alpha-chloralone-anesthetized cats. Occlusion of the LAD artery produced  arrhythmia in all of the animals, with 39% developing ventricular fibrillation (VF). Epinephrine content in the adrenal venous blood increased 5-fold immediately after occlusion and was associated with the development of arrhythmia and VF. The adrenal venous epinephrine levels increased 8-fold after occlusion in the animals that developed VF while, in those that did not develop VF, the epinephrine levels increased only 1.5-fold. Bilateral ligation of the adrenal veins 1 hour prior to occlusion of the LAD artery did not alter the pattern of development of arrhythmia but prevented the occurrence of VF. Pretreatment of animals with either practolol or sotalol 15 min prior to LAD artery occlusion also did not affect the occurrence of arrhythmia but prevented the incidence of VF. The data indicate that acute occlusion of the LAD coronary artery produces a sharp rise in epinephrine from the adrenal medulla and that epinephrine is a major factor in producing VF but does not seem to be involved to any great extent in the production of less ominous ventricular arrhythmias.


Effect of deep hypothermia, limited cardiopulmonary bypass, and total arrest on growing puppies.

The advantages of a bloodless field and total cardiac relaxation have popularized the technique of deep hypothermia and total circulatory arrest for the correction of complex congenital cardiac defects in infancy. There is, however, a significant potential for cerebral and pulmonary complications. Presently, the most common technique is that of using a combination of surface cooling and cardiopulmonary bypass cooling and rewarming. Normal neurological development has been claimed with the present technique of hypothermia at 20 degrees C and total circulatory arrest for periods up to an hour; however, there are reports of seizure activity in the early postoperative period. There is also a disturbing incidence of respiratory insufficiency and, occasionally, hemorrhagic pulmonary edema. This study, using growing puppies and subjecting them to deep hypothermia and total circulatory arrest for varying periods of time, disclosed that animals subjected to 60 min of circulatory arrest recovered neurologically; however, there were histological changes of anoxia in the brain. Animals subjected to 30 min of total circulatory arrest were normal neurologically and there was no histological evidence of anoxic damage to brain tissue. Puppies that were continuously on cardiopulmonary bypass had no significant pulmonary changes caused by increasing the inspired oxygen tension in the ventilator; however, striking changes were noted when limited cardiopulmonary bypass was employed for core cooling and total circulatory arrest combined with pulmonary ventilation with 100% oxygen. We conclude from this experimental study that the use of surface cooling and core cooling with subsequent total circulatory arrest at 20 degrees C is a safe procedure, providing the period of time of cardiac arrest is kept around 30 min. We also conclude that the alveolar oxygen tension should be maintained at the lowest level possible during the interval of circulatory arrest to avoid the apparent rapid onset of post-traumatic pulmonary insufficiency.


Consequences of reperfusion following acute coronary occlusion.

The sequential effects of reperfusion following acute intracoronary balloon occlusion were investigated in closed-chest anesthetized dogs by simultaneous measurement of hemodynamics and regional metabolism and histopathologic study. Simultaneous regional determinations of myocardial metabolic function were carried out in coronary-occluded and nonoccluded segments of the left ventricle. A 3-hour occlusion of the proximal left anterior descending coronary artery (LAD) resulted in significant decrease in cardiac function. Intitial reperfusion was marked by major washout of metabolites and development of frequently serious arrhythmias. Reperfusion following 3 hours of LAD occlusion led to futher deterioration in hemodynamics and metabolism: 30% of the dogs developed shock. Lactate extraction decreased further in the nonoccluded region and reached production levels in the occluded zone. Potassium loss increased in both zones. Oxygen extraction remained unchanged. Pathophysiologic examination of tissue specimens from the reperfused zone revealed microthrombi, patchy necrosis, fragmentation of myofibrils, vascular congestions, and hemorrhages.


Demonstration of the "no-reflow" phenomenon in the dog heart after temporary ischemia.

The effect of 40- or 90-min periods of temporary myocarardial ischemia on the distribution of coronary flow and capillary structure were assessed in groups of mongrel dogs. Thioflavin S. a fluorescent dye which stains vascular endothelium when injected intravenously, was used to demonstrate the distribution of microvascular perfusion at 10 sec, 5 min, or 20 min following release of a 40-or 90min circumflex coronary artery occlusion. Hearts which demonstrated perfusion defects were sampled for electron microscopy. Following 40 min of occlusion, thioflavin S was distributed uniformly throughout the myocardium. In contrast, following 90-min periods of coronary occlusion, perfusion defects always were present in the subendocardial half of the posterolateral left ventricular wall. Several morphological features in these areas of no reflow were observed by electron microscopy, including decreased endothelial pinocytotic vesicles, endothelial gaps and bleb formation, capillaries packed with erythrocytes, occasional intraluminal thrombi, and extravascular erythrocytes and fibrin. Myocardial cells showing severe injury always were seen within but also extended beyond the areas of poor perfusion. These results demonstrate that areas of no reflow occur following 90-min periods of ischemic injury in the dog, but that primary myocardial cell injury occurs during the ischemic period and not as a function of the "no-reflow" phenomenon.


Regional differences in fatty acid oxidation by the adult rabbit myocardium.

Differences in coronary perfusion and tissue oxygenation between the epicardium and endocardium have been shown. Thus, intrinsic capacity for substrate oxidation may also exhibit regional variation. Accordingly, homogenates of left ventricular papillary muscle ("endocardium") and left ventricular free wall trimmed of endocardium ("epicardium") were compared for their capacity to oxidize palmitic acid-1-14C (PA) and octanoic acid-1-14C (OcA). Homogenates from one to three rabbits were combined for each study; 18 studies were performed using PA, and 10 using OcA. The protein content of endo- and epicardial homogenates was the same (Biuret method). At ambient PA concentrations of 0.2 mM, oxidation of PA by "endocardium" was 64 +/- 6.3% that of the "epicardium" (p less than 0.001). At ambient concentrations of 1.0 mM, oxidation of OcA by "endocardium" was not different from that of "epicardium" (118 +/- 10.5%; p greater than 0.1). Thus, the oxidative capacity for long chain FFA by the endo- and epicardial homogenates are at variance. Differences in carnitine-mediated transmitochondrial transport of long chain fatty acids may be the explanation. Such regional metabolic differences could play a role in regional alterations in myocardial function under adverse hemodynamic and metabolic circumstances.


Changes in sichemic coronary vasodilation produced by blood, plasma, and saline infusions.

Reactive hyperemia was diminished when blood of varying oxygen content was infused into the vascular bed distal to an occluded coronary artery. The degree of response appeared to be related to the oxygen content of the infused sample. However, plasma and saline infusions also caused a reduction in reactive hypermia. It is therefore possible to conclude that the prevention of the fall in intravascular pressure plays an important role in the regulation of vascular smooth muscle tone in the dog heart.


Time-dependent changes of collateral coronary reactivity in the dog.

Vascular reactivity of the developing coronary collaterals has been investigated by studying local flow responses elicited by adrenergic and hypoxic stimuli in the ischemic foci of the canine heart. Tissue blood flow was measured by means of the heat clearance technique. The myocardial area explored was rendered ischemic by ligating the left anterior descending coronary artery 2-90 days prior to the experiment. This area is supplied exclusively by collateral channels. Adrenergic sensitivity was tested by i.v. administration or noradrenaline and isoproterenol (1 mug/kh), as well as by supramaximal electrical stimulation of the stellate ganglion. Metabolic sensitivity of the vessels was tested by brief periods of general hypoxia. During the first 3 weeks of the myocardial infarction, the collateral vascular response induced by each form of the adrenergic activation was considerably different from that observed in the normal coronary bed: instead of the conventional beta-type dilation, noradrenaline and stellate stimulation induced constriction in the ischemic zone whereas isoproterenol, having only pure beta-stimulating effects proved to be ineffective. Following the 3rd postoperative week, a gradually increasing sensitivity to beta-dilator influences appeared on the collateral vessels. However, this transformation of the adrenergic effect was not accompanied by a similar restoration of the local vascular propensity for metabolic (hypoxic) dilation. The results suggest that time courses of the changes of the adrenergic and metabolic vascular reactivity in the collateral network, although probably interrelated, do not parallel each other.


Hemodynamics and metabolic determinants of distribution of myocardial flow.

A computer simulation of the left coronary outflow response to branch occlusion was carried out, using physiological data derived from canine left coronary artery generated on an IBM 360/44 in order to provide multidimensional analysis of the problem of the distribution of flow within the myocardium. During coronary occlusion in this computer model, distal impedance varied little during the occlusion of one or the other arterial brance. This observation was taken as a boundary condition in the simulation exercise. Some of the important factors in the intramyocardial distribution of flow are discussed.


Studies of regional myocardial perfusion in patients with coronary atherosclerosis, using xenon-133 and a multiple crystal scintillation camera.

Regional myocardial perfusion was measured in 164 patients at coronary arteriography. Washout of xenon-133 from multiple areas of the heart was monitored with a multiple crystal scintoooillation camera after tracer injection int the left or right coronary artery. Rate constants of radioisotope clearance were computed by monoexponential analysis of the initial portion of each washout curve. Regional myocardial blood flow rates in ml/100 g.min were calculated by the Kety formula. The pattern of local myocardial perfusion rates was compared to the coronary arteriogram obtained during the same study. In patients with normal coronary arteriograms, the average mean myocardial perfusion rate in the left ventricle (LV) significantly exceeded that of the right ventricle and the right atrial area. Mild heterogeneity of local myocardial flow rates in the LV was observed. In patients with essential hypertension, aortic stenosis, and aortic insufficiency, the average LV perfusion rates were similar to those of subjects with normal coronary arteriograms, pressures, and ventriculograms. The mean LV perfusion rates were significantly reduced in patients without coronary disease who had cardiomyopathy and cardiac failure.


Local myocardial blood-flow measured by the use of a needle-type Pt-H2 electrode.

In order to measure local myocardial blood flow respectively, a needle-type recessed Pt electrode sealed in a thin injection needle was constructed. By means of this electrode, the myocardial blood flow in the inner and outer portions of the anterior wall of the exposed left ventricle of anesthesized dogs was studied. Under conditions, the blood flow in the inner portion (112.4 ml/100 ml/min) exceeded that in the outer portion (98.7 ml/100 ml/min). But the blood flow distribution expressed in terms of the blood flow ratio in both portions was readily varied by several pharmacological treatments, starvation, or prolongation of the experiment. Combining these observations with the results obtained in the decrease of the O2 current in the coronary occlusion test, the following possibilities seemed probable: 1) The myocardial blood flow under normal conditions was so distributed that the inner layer could be supplied with an increased blood flow and more oxygen. 2) Such a balance between the local blood flow and O2 demand can often be disturbed under various conditions, as was seen in the case of isoproterinol infusion in the present study.


Mass spectrometry for the measurement of intramyocardial gas tensions: methodology and application to the study of myocardial ischemia.

The methodology for use of the mass spectrometer for the measurement of intramyocardial gas tensions in the canine preparation is described. Baseling studies were carried out initially in 36 animals, and control levels for myocardial oxygen tension and myocardial carbon dioxide tension were 19 mm Hg (S.D. 6 mm Hg) and 43 mm Hg (S.D. 10 mm Hg), respectively. Myocardial oxygen tension was not altered significantly by varying the arterial oxygen tension between 65 and 300 mm Hg. However, myocardial carbon dioxide tension increased linearly with increased arterial carbon dioxide tension. In 15 dogs placed on total cardiopulmonary bypass, a perfusion pressure 40-60 mm lower than the control mean arterial pressure resulted in myocardial ischemia with a decrease in myocardial oxygen tension and an increase in myocardial carbon dioxide tension. A subsequent increase in perfusion pressure to control levels resulted in resolution of ischemia and return of myocardial oxygen and carbon dioxide tensions to their control level. In another series of open-chest dogs on cardiopulmonary bypass, a proximal constriction applied to the left coronary circumflex artery resulted in a marked decrease in myocardial oxygen tensions and a marked increase in myocardial carbon dioxide tensions in the region supplied by the constricted vessel. In yet another series of open-chest dogs, it was found that incremental decreases in coronary flow established by constriction of the circumflex artery resulted in an exponential increase in both myocardial  carbon dioxide tensions and ST-segment elevation as determined by a 25-gauge multi-contact plunge electrode placed in the posterior left ventricular wall. It appears that mass spectrometry techniques for evaluating myocardial ischemia have several advantages over myocardial biopsy techniques for assay of ATP and lactate, and also over the technique of coronary sinus lactate determination.


Effect of conditioning on myocardial metabolism after myocardial infarction.

The present study was conducted to evaluate the effect of prior physical training on metabolic changes after isoproternol-induced myocardial infarction in albino rats. The evaluation was done in terms of serum transaminases (SGOT and SGPT), serum lactic dehydrogenase  (LDH), serum creatine phosphokinase (CPK), cardiac glycogen, and cardiac noradrenaline. Male albino rats weighed 100-150 g were selected for the study. Physical training (conditioning) consisted in making the animals swim in a tank of water for 60 min daily on 6 days a week, for 8 weeks. Myocardial infarction was produced by subcutaneous injection of isoproterenol, 85 mg/kg body weight, on 2 consecutive days. There was significantly less elevation of SGOT, LDH and CPK in the conditioned group after myocardial infarction; the rise in SGPT was not significantly different in the two groups. A smaller rise of serum enzymes revealed less myocardial damage in the conditioned group; the rise in FFA was also less in the conditioned group, a more favorable situation for an ischemic myocardium. No significant difference was observed in cardiac glycogen and cardiac noradrenaline after isoproterenol-induced cardiac necrosis. The significance of these observations is discussed.


Inhibition of extracellular and purified 5'-nucleotidase from rat heart.

5'-Nucleotidase in perfused rat hearts, accessible to extracellular substrate [14C]-AMP contained in the perfusate, was compared to a partially purified 5'-nucleotidase from the same organ. Both activities were inhibited by ATP and, more effectively, by the ADP analog adenosine-alpha, beta-methylene diphosphate (APCP). The isolated enzyme showed a competitive inhibitor constant of 5.4 x 10(-8) M for APCP (Km of AMP = 1.4 x 10(-5) M). Although both activities were effectively inhibited by APCP, insufficient knowledge about the selectivity of this agent as a nucleotidase inhibitor does not permit a conclusion on whether or not the extracellular activity is identical to the partially purified enzyme.


Comparative in vitro and in vivo studies on the effects of tricyclic antidepressants on myocardial contractility.

The effects of the similarily structured antidepressant drugs imipramine and dimetacrine and their demethylated derivatives on myocardial performance were studied in vitro on 42 right ventricular papillary muscles of cats. The hemodynamic effects of intravenous administration of 22 mg of free base imipramine and dimetacrine were investigated in 12 patients with coronary disease. The results of the in vitro studies show that imipramine greater than dimetacrine greater than desmethyl compounds have a marked dose-dependent negative inotropic effect on all parameters of myocardial contractility, i.e., afterloaded isotonic contractions (delta L), dL/dtmax, dL/dtmin,dT/dt. The hemodynamic investigations indicate that imipramine greater than dimetacrine induces a significant increase in end-diastolic left ventricular pressure. Both drugs increase mean arterial blood pressure, correlated to a peripheral vasoconstriction and corresponding to an increase on the plasma level of catecholamines. It is concluded that both effects of these antidepressant drugs (reduction of myocardial performance and an increase in the plasma level of catecholamines) must be considered a risk in patients predisposed to myocardial failure.


Contractile apparatus in aortic endothelium of hypertensive rat.

One week after hypertension was produced in male Wistar rats (150 g body weight) by a complete aortic ligature placed between renal arteries, electron microscopic studies showed a striking increase of cytoplasmic microfilaments in the endothelial cells of the aortic segment above coarctation (mean blood pressure 160 mm Hg). These microfilaments measured 40-70 A in diameter and were located particularly close to the endothelial clefts. In "en face" preparation of aortic endothelial cells treated with antiactin autoantibodies (AAA) followed by antihuman IgG, the cells above the ligature of hypertensive animals were intensely fluorescent compared with those of the aortic portion below the ligature or that of controls. The fluorescence was abolished after incubating the AAA-containing sera with thrombosthenin-A, suggesting the presence of actin. There was also an increase transport of horseradish peroxidase and ferritin through the endothelial cell layer. While endothelial cells so modified may play a role in permeability regulation, they may also be related to such mechanisms as electronic coupling and synchronized contraction of aortic cells during hypertension.


Light and electron microscopic study of cellular proliferation in carcinoid heart disease.

An ultrastructural and histochemical study of the subendocardial lesion in carcinoid heart disease showed six different cell types within a myxoid matrix. The matrix, composed of a mucopolysaccharidic ground substance, collagen, and reticluin fibers, contained stem cells, four types of fusiform cells (fibrocytes, fibroblasts, myofibroblasts, and smooth muscle cells), and intermediary cell type. Our observations suggest that the humoral mediators of the carcinoid syndrome may induce the differentiation of a subendocardial stem cell into contractile elements.


Age-dependent changes of heart valves and heart size.

The mode and extent of the regressions of heart valves, valvular rings, and tendon chords, as well as the size of atria and ventricles in 316 hearts of different age groups (macroscopically normal at autopsy), were studied. With increasing age, the valves showed marked thickening and loss of elasticity. Deposition of lipoids and calcification occur to a variable extent in the valvular tissue and rings; Valve size shows a change of minor degree, but tendon chords and papillary muscles shorten in old age. The diameters of the atria, mitral, tricuspid, pulmonary, and aortic rings increase continuously up to the 9th decade of life. The width and length of the ventricles show minor alterations in size. In old age, heart weight increases.


Method for the production of severe ventricular dysrhythmias in small laboratory animals.

In earlier reports from this laboratory, it was shown that 3 weeks' pretreatment with desoxycorticosterone acetate (DCA) pellet implantation and saline as drinking fluid caused a nearly 20,000-fold potentiation of the acute cardiotoxicity of isoproterenol. In such animals, the beta-receptor stimulant consistently elicited severe ventricular dysrhythmias, usually leading to ventricular fibrillation (VF) and death. In the present study, a similar enhancement of isoproterenol arrhythmogenic activity after DCA-saline pretreatment was demonstrated also in the guinea pig and albino mouse. It was found, further, that isoproterenol consistently caused an alteration of the total myocardial electrolyte content in DCA-saline-treated rats, consisting of a decrease of magnesium (Mg) and potassium (K) levels and elevation of sodium (Na). In control rats, on the other hand, isoproterenol did not alter the myocardial Mg content and increased K. The emertence of cardiac irregularities and VF could be inhibited by pretreatment with antiarrhythmic drugs. On a molar basis, these agents decreased the incidence of VF in the following descending order: dl-propranolol (100), practolol (39), d-propranolol (34), sotalol (20), quinidine (8), and lidocaine (5). In the presence of any of the listed drugs, except for lidocaine, isoproterenol did not lower Mg levels and had variable effects on those of Na and K. Pretreatment with Mg gluconate was likewise effective in preventing isoproterenol-induced dysrhythmias and death. These findings demonstrate that: a) sensitization of the myocardium by DCA-saline treatment is not species-specific for the rat; b) this phenomenon can be a useful method for the screening of antiarrhythmic drugs; and c) isoproterenol-induced dysrhythmias may be associated with myocardial electrolyte alterations involving especially Mg depletion.


Lesions of the conduction system in the cat with cardiomyopathy.

Degeneration and fibrosis of the atrioventricular nodal tissue and left bundle branch, associated with cartilage of bone in the central fibrous body and fibrosis of the interventricular septal crest, were observed in 63 cats with cardiomyopathy. The cardiac lesions consisted of endocardial and myocardial fibrosis or organized endomyocarditis. Electrocardiographic, radiographic, angiocardiography, and hemodynamic changes were also observed in the cats.


Protective effect of coexistent thiamine deficiency upon the experimental cardiomyopathy associated with acute magnesium deficiency in the Syrian golden hamster.

Repeated efforts to induce beriberi heart disease by experimental thiamine deficiency (B1d) have failed in many species. To test the hypothesis that magnesium deficiency (Mgd) might be the cofactor necessary for heart failure, 10-week-old Syrian golden hamsters were divided into four groups-control (C), B1d, Mgd, and combined MgB1d-and were fed the diets ad libitum for 3 weeks. On day 21, animals were studied under intraperitoneal pentobarbital anesthesia (50 mg/kg). Electrocardiograms were taken and right and left ventricular pressures were measured by transthoracic needle puncture. Cardiac output was measured by the direct Fick method. The complete study was performed in 9 C, 13 B1d, 9 Mgd, and 14 MgB1d animals. B1d was proven by low red blood cell transketolate high B1 pyrophosphate effect, and was accompanied by tachycardia and hypercalcemia. B1 did not differ from C in any other parameter. Mgd was characterized by hypomagnesemia, hypercalcemia, prolongation of the PR interval, widening of the QRS interval, low O2 consumption, low cardiac output, and increased heart weight to body weight ratio (HW/BW) as compared to control. No differences were observed in right and left ventricular pressures or peak /dt. MgB1d was characterized by hypomagnesium, hypercalcemia, low red blood cell transkeotlase, and high B1 pyrophosphate effect. MgB1d minimized the deleterious effects of Mgd: animals were more active and the mortality was low, the PR interval remained normal, the QRS interval widened significantly less, cardiac output remained normal, and HW/BW increased significantly less. Although, once again, beriberi heart disease was not produced, B1d appeared to exert a protective effect upon the Mg-deficient myocardium.


Iron supplementation in suckling rats: its effect on the heart.

The present study attempted to determine the significance of the "anemia" which normally occurs in infants. We compared various parameters in suckling rats whose hemoglobin concentration had been artificially raised by gastric tube feeding of iron with those of control animals. The 20-day-old experimental animals showed significant increases in the weights of the liver (10%) aan spleen (40%). They had also developed a statistically significant 8% increase in heart weight, accompanied by a smaller myocardial fiber size and, thus, higher fiber density. The association in these young animals of higher than normal hemoglobin levels with smaller hearts and myocardial fibers suggests that the normally developing "anemia" of infancy may well serve an important physiological function: to stimulate myocardial growth.


Effect of thyroparathyroidectomy and of a low calcium diet on the cardiomyopathy of the Syrian hamster.

Experimental Ca deficiency in the cardiomyopathic Syrian hamster was found to be effective in reducing the incidence and the severity of the heart lesions that develop at 30 days of age. The skeletal muscle changes that develop at a much earlier period were influenced in their course but not in their frequency. It was further observed that 20-day-old animals benefit better from a low Ca intake at a time when the degenerative changes do not prevail in the myocardium. Removal of the parathyroids in normally fed myopathic hamsters had no effect on the serum calcium and phosphate levels or on the course of the disease. The serum creatine phosphokinase was found to be higher in Ca-deficient myopathic hamsters. The possible role of calcium concerning the maintenance of the integrity of the muscle cells is discussed.


Vesicular myocardial change: an ultrastructural study of double membrane-bound vesicles in the human heart.

Vesicular myocardial change is a specific and common finding in the diseased hearts of humans and experimental animals. The small to large vesicles are generally bound by a double membrane. They are formed within myocardial cells and then possibly extruded into the extracellular space where they disintegrate or are phagocytosed by mononuclear cells. On the basis of our studies, most vesicles appear to be of mitochonrial origin. In humans, vesicular myocardial change appears to be most extreme in primary cardiomyopathy. It may also be present, but in lesser degree, in the apparently normal hearts of human adults. Vesicular myocardial change probably represents a specific mechanism by which myocardial cells eliminate damage mitochondria or other undesirable elements that build within them as a result of disease, aging, and perhaps normal physiological activity.


Time course of mechanical activity in mammalian cardiac muscle: dependence on species, loading, and displacement.

We have found that animal species is of great importance when mechanics of contraction are analyzed in mammalian cardiac muscle. Mechanics of contraction have been studied comparatively in the isolated papillary muscles of the rat, cat, and rabbit under control conditions and following alterations of loading and inotropic interventions. The time course of the shortening ability measured in terms of the velocity of shortening at constant contractile element length and load following quick releases to preload peaked at 20, 30, and 70% of time to peak force (TPF) in the rat, cat, and rabbit, respectively, and declined more slowly in the rabbit. The shortening ability peaked progressively later in contraction at increasing loads in the cat, but not in the rabbit. Shortening ability measured after releases to zero load or after imposing "load clamps" of variable magnitude and duration reached the maximum much later in the rabbit than in the cat. The contractile response to changes of the contraction mode from isometric to isotonic was different in cat and rabbit. Upon increase in the stimulation rate from 6 to 60/min, force increased to a greater extent in the rabbit than in the cat, while TPF did not decrease in the rabbit as seen in the cat. Caffeine (10mM) increased developed force more in the rabbit than in the cat, while even 1 mM caffeine decreased force in the rat. The onset of the shortening ability was greatly delayed by caffeine in the cat and rat but not in the rabbit. Afterloaded force-peak velocity relations were curvilinear in the cat and rat; these relations approached linearity in the rabbit in the control state, and in both cat and rabbit in the presence of caffeine. The differences in the mechanics of contraction, in the contractile response to alterations in loading, and to caffeine in the ventricular muscle of the rat, cat, and rabbit are viewed as indicators of differences in excitation-contraction coupling of ventricular cardiac muscle from these different mammalian species.


[Familial form of cutaneous epitheliomatosis with complex neurological characteristics similar to hereditary spinocerebellar degeneration. Apropos of 4 cases including one case with anatomo-clinical description].

The authors report an observation in which four siblings were affected by both multiple cutaneous epitheliomatosis and complex but relatively stereotyped neurological disorders. Clinically, the main syndrome was cerebello-spinal ataxia with involvement of the anterior horns of the spinal cord with less marked pyramidal and extra-pyramidal features. Neuropathological examination of one of the cases revealed lesions of essentially cerebello-spinal degeneration suggestive of Menzel's disease. The possible connection between the neural and cutaneous lesions is discussed. All the various etiological categories possible have been ruled out; not one being entirely satisfactory, except for the very broad category of genetic neuro-dermatoses.


[Leukodystrophy with adrenal insufficiency (adreno-leukodystrophy). A study of 3 familial cases with the ultrastructure of one biopsied case].

Three male siblings in a gypsy family presented with congenital Addison's disease. The youngest showed neurological signs at the age of ten and deteriorated rapidly. The eldest had convulsive symptoms and the third an irregular E.E.G. Investigation of the youngest by means of cerebral biopsy revealed rarefaction of myelin with perivascular sudanophil deposits. An ultrastructural study showed frequent liposfuscin deposits in the astrocytes and oligodendrocytes. In the peripheral nerve there were signs of re-myelinization associated with hypertrophy of Schwann cells. These various aspects have led to these cases of demyelinization associated with adrenal deficiency being classified among the leukodystrophies while some authors have interpreted these lesions as characteristic of Schilder's disease. The fact that in thirty or so cases published, almost half of which are familial, only boys are affected supports the theory of an enzymopathy at the root of both leukodystrophy and adrenal atrophy.


[Cutaneous elastopathy and vascular anomalies associated with neurological disorders. Apropos of 2 cases].

The two cases described exhibited elastopathy associated with arterial stenosis (case 1) or aneurysms (case 2). The first was clearly a case of elastic pseudo-xanthoma with characteristic cutaneous lesions associated with retinal angioid streaks and severe arterial lesions, notably stenosis of the vertebral arteries (especially the left) causing disorders in the mechanism of balance. There were, in addition, mild diabetes, hyperlipidaemia and abnormal cutaneous pigmentation. The second patient, an African, had been hospitalised for an optochiasmatic syndrome which further investigation, notably by arteriography, indicated was caused by compression of the visual pathways due to  massive bilateral carotid aneurysms. The patient had molluscoid pseudo-tumours of the axillae and she reported that her father was in the same condition. Although in the first case, cutaneous biopsy enabled diagnosis of systematized elastorrhexis to be confirmed, histological investigation in the second case revealed mainly hyaline sclerosis of the deep dermal layer. The diagnosis of Ehlers-Danlos disease, suggested for this second patient, could not be confirmed. These two cases emphasize the possibility of various neurological disorders occurring in the course of dystrophy of the connectivo elastic tissue.


[The Cis AB complex of the ABO system].

Members of six unrelated families from Japan, France, Belgium and Poland were studied in parallel. Major immunological features characteristic of the phenotype produced by the Cis AB complex are the following: 1) The red cell A reactivity is close to normal, is beyond the values of agglutination scores by Helix and by anti-A from B; likewise, with percent agglutination measurements, A reactive appears hiher than that of A2B cells; one sample only is slightly detected by anti-A from Dolichos. 2) The B reactivity, on the contrary, is lower than that of normal AB cells. A single sample is detected by anti-B from A1. All samples are well detected by anti-B from AW, Aend, Ax, Am but none is detected by anti-B from ABx, Cis AB, or by an auto-anti-B. Under standard conditions, percent aggutination is around 80, very close to that of normal AB cells, thus differentiating Cis AB from AB3 (some of which only reach this figure), and from ABx which are very far from this value. 3) An abnormally high reactivity to anti-H antibody is observed, higher than that of normal A2B, similar to that of A2 red cells. 4) Among secretors, A substance is found to be normal or in excess, H substance is in excess, while B substance is only detected by Cis AB red cells inhibition. 5)An anti-B antibody was identified in the samples studied; however, we recently received from Germany a Cis AB samples, the serum of which did not contain anti-B antibody. By these main characteristics, the studied samples seem to be identical; however, agglutination kinetics and thermodynamic methods show that they differ by their reaction with a same anti-B antibody in standard conditions. The reactive structures of the various samples are indeed different from one family to another. The main point is that identical values were observed in all samples within a same family. Thus, the various Cis AB can be considered as different families mutants.


[Cold agglutinin with anti-B specificity in an A1B subject].

A high titre cold autoagglutinin with anti-B specificity was found in the serum of an A1B group individual. It was associated with a low titre anti-I. This anti-B agglutinated most cells having a B antigen (normal B, A1B, A2B, from adult and cord bloods, B3), but failed to agglutinate Bx Cis-AB and Bh cells. Nevertheless, all these cells absorbed the anti-B SER  at low temperatures. Fixation elution tests were also positive on the patient's cells and three consecutive absorptions on these cells completely removed the anti-B activity. The Coombs test was positive with anti-complement anti-globulin when the cells were sensitized by the serum at 4 degrees C. It was negative when the cells were sensitized at 37 degrees C. The patient did not show any sign of haemolysis. The anti-B was a IgM Kappa. Its reaction with normal B cells had an enthalpy change of - 36-000 cal./mole, i.e. very different from O ANd A individuals, but similar to that of the erythrocytic I antigen - anti-i antibody reaction. Quantitative measurements showed the erythrocyte B antigen similar to that of control A1B cells.


[The coxopathies of Paget's disease. Radio-clinical and anatomopathological study].

A systematic study was carried out on 105 patients with Paget's disease (60 men and 45 women, average age 62 years) involving the acetabulum and/or the femoral head in the juxta-articular zone. In two-thirds of the patients only the pelvis (in particular the acetabulum) was affected, in a quarter both the pelvis and the femoral head were affected, and in one case in ten only the femoral head. 1. 18 coincidental coxopathies should first be excluded (12 coxarthrosis, 2 coxitis, etx.). The occurrence of 17 percent of coxopathies not caused by Paget's disease is normal in older patients (Vignon and Jacquet; Sebban, Lequesne et al.). 2. In 105 cases, there were only 50 coxopathies really due to Paget's disease, of which almost half remained painless. 3. This proportion did not vary with age. On the other hand, coxopathy was more frequent in patients with bipolar, pelvifemoral Paget's disease and above all in Paget's disease with acetabular protrusio. 4. The radiographic appearance is slightly different from that of coxarthrosis; the reduction in joint space is more often internal or supero-internal (50 percent of cases); osteophytosis is usually moderate (22 percent of cases), or absent (48 percent). The geodes are rarely visible : 6 percent of cases. 5. The acquired bone deformations in patients with Paget's disease are classical. In 105 cases, the authors noted 14 acetabular protrusions, all with coxopathies, and 10 coxa vara, 5 of which had coxapathies. Anatomo-pathological studies did not reveal anything in particular about the bone : superimposition of the Paget's disease lesions and of the lesions usually found in cases of coxopathy due to overload, with a dense pressure cone. With reference to cartilage, the lesions of Paget's coxopathies presented several specific characteristics compared with those of common arthrosis : (1) the presence of particularly numerous cupshaped defects on the remaining cartilage; (2) a very basophilic, intra- and extra-cytoplasmic substance impregnated the chondroplasts of the bottom layer, nine times out of twenty-six, an anomaly not observed in cases of arthrosis; (3) pseudo-angiomatous vascular outgrowths from the bone, flush with the articular surface of the acetabulum are a source of bleeding during surgery.


[Diffuse articular chondrocalcinosis and Paget's disease].

At the time of a personal observation of Paget's disease associated with a diffuse articular chondrocalcinosis (ACC) in a 75-year-old man suffering from diabetes and hyperuricaemia, the authors re-examined 61 patients suffering from Paget's disease to look for this association which had been previously mentioned by Radi et al. with the unusual frequency of 42 percent of cases. In 52 percent of their patients, who had undergone complete radiological examination of the skeleton, the authors found only one case of ACC, or 1.9 percent. Taking into account the respective frequencies of Paget's disease and of diffuse ACC in the general population aged more than 40 years, the results of this careful study led the authors to conclude that an association of ACC and Paget's disease is due to chance.


Total body potassium measurements in 230 patients. A study of potassium depletion.

Three groups of patients with suspected potassium depletion were studied. Twenty-nine obese patients were observed before and up to 1 year after an intestinal shunt operation. During the first week after operation they lost almost 3 grams of potassium per day. The percentage potassium loss was much larger than the percentage weight loss. A significant decrease of serum potassium was also noted during the first week after operation. In contrast to the total body potassium, however, the serum potassium remained within normal limits in all patients except two. Fourteen patients subjected to a cardiac operation also showed a significant decrease of total body potassium concentration 1 week after operation. The serum potassium remained within normal limits. In 187 patients with suspected potassium depletion the total body potassium had been measured, and the results were examined retrospectively. In 38 of these patients the measured total body potassium was outside a 94% confidence interval for an individually predicted value, even though 26 of these 38 patients were taking oral potassium chloride tablets. In 23 of these 38 patients two or three risk factors - hypoalbumin-emia, treatment with diuretics, and treatment with digitalis - were present simultaneously, and in 10 patients one factor was present. Only 8 of the 38 patients had a low serum potassium value. It may therefore be concluded that the total body potassium measurement, when compared with an individually predicted value, seems to be more sensitive in estimation of potassium depletion than the commonly used serum potassium method.


Mechanisms in acute oliguric renal failure induced by tetracycline infusion.

Tetracycline hydrochloride (TC), 30-70 mg/kg infused intravenously in dogs in the course of a few minutes, reduced clearance of inulin (Cin) and p-aminohippuric acid (CPAH) on an average to less than 5% of control. In spite of increased intrarenal pressure (approximately 50 mm Hg), electromagnetically recorded renal blood flow was preserved, indicating that the reduction of Cin and CPAH resulted from tubular obstruction, not renal vasoconstriction. The metabolic rate of the cortex and outer medulla fell to 69% of control after TC, as measured by the heat accumulation rate. Further reduction to basal metabolic level (30% of control) was reversibly produced by elevating ureteral pressure, suggesting that the high metabolic rate was caused by continued active reabsorption of sodium chloride at about half the control rate. Thus Cin greatly underestimated glomerular filtration rate in the TC-damaged kidney. From these results and the observation of TC-containing casts in the medullary tubules, we conclude that TC caused tubular obstruction and that leakage of inulin and PAH from the tubules occurred mainly distally to the major sodium-reabsorbing tubular segments.


Wash-out of intraparenchymally injected Xenon-133 as a parameter of liver blood flow in the dog.

The method of intraparenchymal injection of xenon-133 for measurement of blood flow was evaluated for use in the liver. Repeated injections in the same liver gave rise to a great range of flow values, pointing to a heterogeneous liver perfusion. The use of single measurements for determination of liver blood flow with this method is not acceptable. Comparison between different livers is only possible when several injections are made and the results are given a statistical characterization. Flow values obtained generally did not correlate well with values determined by other methods. The method therefore seems suitable only for comparative and qualitative studies.


Compensation for geometric changes during monitoring of 133Xe washout from subcutaneous adipose tissue.

A method is described for automatic compensation of changes in geometry during monitoring of 133Xe-washout curves from subcutaneous depots. A 99mTc source is placed on the skin over the 133Xe depot, and both isotopes are counted simultaneously. Variations in the 99mTc activity (corrected for radioactive decay) reflects changes in counting geometry and efficiency and are used for correction of the 133Xe elimination curve. The method permits accurate elimination curves to be obtained from subjects exercising on a bicycle ergometer or running a treadmill.


The influence of fatty acids on serum thyroxine determination by competitive protein-binding radioassay.

Thyroxine concentration, determined by competitive protein-binding radioassay (T4(D)), increased in serum stored at 20 degrees C and 37 degrees C. The increase correlated well with the increase in nonesterified fatty acids (NEFA). In vitro addition of NEFA to serum and in vivo increase in NEFA induced by post-prandial heparin injection resulted in a proportional increase in T4(D) values. Protein-bound iodine and thyroxine concentration, as determined by radioimmunoassay, were not influenced by storage and changes in NEFA concentration. NEFA interfere with T4(D), leading to elevated results.


Evaluation of an in vitro assay of lecithin:cholesterol acyl transfer rate in plasma.

Crucial and previously criticized points in a slightly modified version of the Stokke-Norum assay of fractional lecithin:cholesterol acyl transfer (LACT) rate in plasma were studied. LCAT activity in the albumin added to the assay medium and negative influence of remaining organic solvent were important sources of error that it was necessary to eliminate. The assumption of equilibration of labeled cholesterol among lipoproteins in vitro was supported experimentally. Addition of isolated chylomicrons had no influence on initial LACT rate. Incubation time was decreased to 20 minutes to obtain a better estimate of initial LCAT rate in normals. Using gas-liquid chromatography to determine unesterified cholesterol concentration, the precision of measurement of molar LCAT rate was 5.2 per cent (coefficient of variation). Molar LCAT rate in healthy males 20-60 years of age was 56-130 mumol-1(-1)-h-1 (mean +/- 2 S.D.) and compared well with reports from other laboratories and in vivo measurements. At present this methodology is considered to be suitable for studies of LCAT and cholesterol turnover in different metabolic situations and clinical materials.


Effect of long-term administration of ethanol to the rat: lipids, collagen and other proteins, and Mallory bodies in the liver.

Rats drank ethanol, on the average 1.20 g/100 g body weight, for various periods up to nearly 300 days. Experimental variables included a high-fat, low-protein diet, administration of additional ethanol by stomach tube, and CCl4 injections instead of ethanol. Growth was retarded by all the variables, especially by the high-fat, low-protein diet. The specific histological finding in the ethanol groups was the presence of Mallory bodies. Significant increase in total liver lipids was caused by ethanol, and rapid fat accumulation, inflammatory changes, and even fibrosis and cirrhosis by the high-fat, low-protein diet and the CCl4 injections. Ethanol raised the concentrations of collagen and soluble protein in the liver; the collagen content was increased also by the high-fat, low-protein diet and the CCl4 injections. The incorporation of proline to collagen was stimulated in incubated liver slices from both ethanol-treated and high-fat, low-protein-fed rats. These treatments also increased the concentration of free proline in the liver, thus augmenting the protein synthesis in fibroblasts.


Diameter of the afferent arteriole in the dog kidney estimated by the microsphere method.

Microspheres with diameters of from 10 to 30 mum were injected into the renal arteries of three anesthetized dogs. The six kidneys were studied by light microscopy. The diameters of the spheres trapped in the afferent arterioles and of all spheres recovered in the kidneys were recorded. On the basis of the distribution of diameters in these two populations of spheres, the average diameter of the afferent arteriole and the distribution of the afferent arteriolar diameters were estimated. The average diameter of the afferent arterioles was 16.3 mum (S.D. 2.2 mum), without any difference between three cortical layers of equal thickness. The mean diameter of spheres trapped in the interlobular arteries was 25.7 mum (S.D. 2.6). It is suggested that the pressure drop along some interlobular arteries may be of physiological importance, affecting the autoregulation of blood flow in the renal cortex.


Relationship between urine flow, glomerular filtration, and urine solute concentrations during prolonged heavy exercise.

Serum and urine electrolytes, creatinine, and urea were determined in 21 well-trained men, aged 21-56 years, in connection with a 70-km cross-country ski race, lasting 4.39-6.52 h, leading to slight dehydration. Although the race urine flow was low, averaging 0.41 (0.1-0.9) ml/min, the average urine concentrations of urea, Na, Ca, Mg, Cl and P were markedly lower than during the preceding night, while the concentrations of K and creatinine were higher, the total of measured solutes being 621 nmol/l, compared with 911 nmol/l during the preceding night. Decreasing urine flow and endogenous creatinine clearance were accompanied by a falling urine solute concentration, particularly when the race creatinine clearance decreased to below 70 ml/min, mainly due to a fall in the urea, Na, and Cl concentrations. Thus, a decrease in the glomerular filtration rate was accompanied by a progressive decline in the urine concentrating ability.


The venomotor response to static muscular exercise.

The venous blood pressure response to static muscular exercise was studied in seven young normal subjects by the occluded-limb technique. A slight pressure increase was obtained during the first seconds of the contraction period. Then the pressure response subsided, and the control level was reached after 1/2-1 1/2 min despite sustained contraction. The response was of the same type as that elicited by a voluntary deep breath, but usually of lesser magnitude. It seems to differ from the response to dynamic muscular exercise, suggesting that a continuous stiffening of the capacitance vessels, to maintain a high venous response, is not needed to the same extent during static muscular exercise. In previous studies a similar pressure increase has been obtained during short-lasting static muscular exercise. The present study shows that this pressure increase is confined to the initial part of the contraction period. Observations made after administration of phenoxybenzamine and atropine indicate that the venomotor response is mediated through sympathetic adrenergic nerves.


Comparison between arm and leg exercise in women and men.

Arm and leg work was performed on bicycle ergometers in sitting position by fourteen women and sixteen men. Heart rate, minute volume of ventilation (VE), and oxygen consumption (VO2) were measured. Arm exercise was performed until (muscular) exhaustion, leg exercise up to a heart rate of circa 170 beats/min. At comparable work loads arm exercise evoked higher VO2, VE, and heart rate than leg exercise irrespective of sex. At comparable VO2, the heart rate and VE were higher during arm work in both sexes, VE more so among the men. With the same limbs working, the mechanical efficiency was equal in both sexes. The regression coefficients of heart rate on load or VO2 was higher for the women irrespective of work type. A close correlation was obtained between working capacity at a heart rate of 170 beats/min (W170) during leg and arm exercise and between W170 of leg exercise and W150, similarly calculated during arm work. Thus W170 of leg exercise could be calculated from either a maximal or submaximal arm work.


A comparative study of meningoencephalitis epidemics caused by echovirus type 7 and coxsackievirus type B5. Clinical and virological observations during two epidemics in northern Sweden.

Two epidemics of meningoencephalitis caused by echovirus type 7 and coxsackievirus type B 5 in the summer and autumn of 1973 in Umeå in Northern Sweden were compared. Most patients with echovirus 7 meningoencephalitis were neck stiff and 50% had a polymorphonuclear pleocytosis in the cerebrospinal fluid (CSF). The illness was usually mild. It appears to be the first time that an epidemic caused by this virus is described from Scandinavia. On the other hand most patients with coxsackievirus B 5 meningoencephalitis showed a more profound involvement of the central nervous system, with abnormal electroencephalograms in 70% and a long convalescence period. The number of cells in CSF was normal in 70% of these patients.


Echovirus type 4 infections in Scotland, 1971-72.

An outbreak of infection due to echovirus 4 in Scotland involving 194 cases during 1971-72 is described. Clinical and epidemiological information was obtained and analysed for 181 patients, of whom 149 (82%) developed aseptic meningitis. The majority of cases were older children (39%) and young adults (40%), although the highest attack rate was in infants (10.5 per 100,000 population). An unusual feature of the outbreak was its biphasic nature with cases occurring largely in the same geographic areas in successive years.


Effects of viral and Mycoplasma infections on the ultrastructure of human skeletal muscle.

The ultrastructure of skeletal muscle from 10 patients confined to bed for about one week with different viral or mycoplasma infections has been studied in the acute phase of the disease and 1 1/2 and 4 months later. Focal deviations from normal ultrastructure were found in the first muscle biopsy. The changes were less pronounced after 1 1/2 months and absent after 4 months. In 5 healthy controls, confined to bed for one week, normal ultrastructure was found on corresponding occasions.


Acute glomerulonephritis complicating Australia antigen-negative viral hepatitis.

A case of acute glomerulonephritis complicating Australia antigen-negative hepatitis in a 17-year-old man is described. The literature relating the onset of glomerulonephritis to virus infection is general, and to that of hepatitis in particular, is reviewed.


Vasectomy for voluntary male sterilisation.

Vasectomy was performed in 90 men in Department of Surgery II of the University Central Hospital of Helsinki during the period January 1st, 1972 to December 31st, 1973. Operation was performed on an ambulatory basis under local anesthesia. After resection and ligation of vas deferens the cut ends were placed in different fascial planes in order to avoid recanalisation. The patients were mainly in the age group 31-40 years. Seven patients had postoperative complications, scrotal hematoma being the most common. Recanalisation was found in one patient, in whom a new operation was performed. The author stresses the importance of a correct vasectomy method, histological verification of the divided vasa and most of all the postoperative sperm analysis. Two negative sperm analyses with an interval of at least 1 month must be recorded before sterility can be confirmed.


Creatine phosphokinase in prostatic tissue.

A histochemical study of creatine phosphokinase (CPK) in the rat ventral prostate revealed that the epithelial cells had a high cytoplasmic activity which was retained or even increased when the cells were atrophic as a consequence of castration. Both the fibromuscular stroma, which is prominent in the ventral prostate of castrated rats, and the secretion had a high level of activity. In human benign prostatic tissue where CPK was present in the epithelium, secretion and stroma, pronounced differences in activity could sometimes be observed between the epithelium of adjacent acini and also between cells in the same acinus. There was no obvious correlation between CPK activity and degree of epithelial hyperplasia. The activity in carcinomatous prostatic epithelial cells varied considerably between specimen from different patients but was uniform within a given specimen in contrast to the variation of epithelial CPK activity within non-carcinomatous tissue. Thus, a difference in the pattern of CPK activity was observed between malignant and non-malignant epithelial cells.


The lobes of the human prostate.

A dissection technique for the huamn prostate has been developed on about one hundred male autopsies, which makes it possible to delimit two dorsal, two lateral and two median lobes, each with separate ducts. It was found that both the dorsal lobesand the lateral lobes join dorsally to the ejaculatory ducts. The median lobes are situated below the medial parts of the seminal vesicles, and are closely apposed both ventrally and dorsally of the ejaculatory ducts. The ability to delimit the prostatic lobes in man may offer new opportunities to study the relation of prostatic diseases to different lobes as well as the hormonal dependency of the separate lobes.


Magnesium and zinc in seminal fluid of healthy males and patients with non-acute prostatitis with and without gonorrhoea.

The concentrations of magnesium and zinc in the seminal fluid of 41 patients with symptoms of non-acute prostatitis and of 11 healthy age-matched males were determined by atomic absorption spectrophotometry. Possible sources of error in the determination of these metals in seminal fluid are discussed. The mean concentration of magnesium in the patients was 56.6 mug/ml (range 19-190) and in the controls 64.5 mug/ml (range 36-165). The corresponding figures for zinc were 79.2 mug/ml (range 13-283) and 67.5 mug/mg (range 34-116). Both in the patients and in the controls there was a significant correlation between the concentration of magnesium and that of zinc. No significant difference was found between the patients and the controls regarding the concentration of magnesium or zinc. From none of the patients could gonococci be cultured. However, in 6 of them, immunofluorescent studies revealed gonococci. The concentration of zinc (48.3 mug/ml) in seminal fluid from these 6 patients was significantly lower than in the remaining 35. Neither in the patients, nor in the controls, was any correlation found between the concentration of magnesium or zinc and that of fructose in seminal fluid. A significant correlation was found between the concentrations of these metals and the antibacterial activity (determined as the inhibitory effect on the growth of Staphylococcus albus) of the seminal fluid from the patients. A negative correlation was found between the concentration of zinc and an increase in the number of white blood cells in expressed prostatic fluid. No correlation was found between magnesium or zinc and the number of spermatozoa or the percentage of abnormal spermatozoa. The findings in the present study suggest that the secretion of magnesium and zinc is decreased in prostatitis. Because of the wide range of variation of magnesium and zinc in seminal fluid of healthy males, determination of these metals is of limited value in the diagnoses of prostatitis in a given case.


The prognostic value of acid phosphatase and beta-glucuronidase activity in biopsy specimens from patients with reactivated prostatic cancer.

The quotient between the activities of acid phosphatase and beta-glucuronidase in biopsy specimens of malignant prostatic tissue varied among 11 patients with reactivated, estrogen-resistant prostatic carcinoma. No correlation was found between the quotient and the therapeutic response to estramustine phosphate. In biopsy specimens obtained after 2 months' treatment, the quotient was lower in those patients who responded to the treatment. Thus, the quotient before treatment is of no prognostic use but diminution of the quotient found after treatment for 2 months is a sign of good clinical effect of the therapy.


Surgical treatment of ureterocele. A follow-up study of 56 operated cases in 52 adult patients.

A material covering 25 years and comprising 52 patients with 56 surgically treated ureteroceles was followed up over periods varying from 3 to 27 years, the average being 12 years. The initial symptoms and treatment are described. Most of the patients were treated with transurethral diathermy incision of the ureteroceles. 10 patients had died before the follow-up and one could not be located. 73% of the remaining 41 patients had no complaints at follow-up and 71% of the patients treated with transurethral incision were symptomatically cured. Vesico-ureteric reflux was demonstrated in 9 patients, of whom 3 had pyelonephritic changes in the kidneys. The groups of patients treated with resection or excision of the ureteroceles were too small to allow significant conclusions.


Urinary protein patterns in patients with uroepithelial tumours. Effect of surgery and radiotherapy.

Albumin, transferrin and immunoglobulins A, G and M were determined in both serum and urine from 84 patients with uroepithelial tumours. There were 76 patients with bladder tumours, of which 19 had previously received radiotherapy and 51 were untreated, whereas the remaining 6 had required a urinary diversion with nephrostomy or cutaneous ureterostomy because of ureteric tumour obstruction. Eight patients with tumours situated in the renal pelvis or ureter were examined, seven of these eight patients could be examined both before and after surgical treatment. The changes in urinary protein patterns were compared with the results of various types of treatment of uroepithelial tumours. A significant reduction in urinary proteins was seen after successful treatment, or when the urinary flow was diverted so that it had no tumour contact.


Recording of intraureteric pressures in women with a new technique.

This paper describes a new technique for recording intraureteric pressures (ureterometry) and its application in the examination of ureteric peristalsis in 20 women. A multichannel catheter, connected to pressure transducers permits recording of the intraureteric pressure simultaneously at three levels, 5-7, 15-17, 25-27 cm from the ureteric orifice. The mean amplitudes of the peristaltic waves at these 3 levels were about 14, 19 and 26 cm H2O, respectively. The peristaltic travel rate averaged 33 mm per second in the lower and 40 mm per second in the upper part of the ureter. This technique was also used to study the ureteral function in women undergoing Wertheim hysterectomy. Moreover it was used to investigate the influence of different drugs and anaesthesias on ureteral motility. Simultaneous ureterometry and ureteropyelography gave the opportunity to correlate the morphology of the ureter to the intraureteric pressure. From consideration of space the results of these investigations are presented elsewhere (Ulmsten, 1974a).


Effects of spinal anaesthesia, lidocaine, and morphine, on the motility of the human ureter in vivo.

A new, sensitive technique for recording intraureteral pressure was used to investigate the effects of spinal anaesthesia, lidocaine, and morphine on ureteral peristalsis in 21 female patients. Spinal anaesthesia, comprising the segments up to ThX-Th III, did not affect ureteral motility, nor did morphine given intravenously in a 15 mg dose. Four to 8 ml 4% lidocaine injected into the renal pelvis, after an initial, brief period of stimulation, markedly reduced ureteral peristalsis. Normal ureteral activity returned within 15-30 min. It is concluded that the activity in extraneous autonomous nerves is of minor importance for ureteral peristalsis, and that morphine, in doses used clinically, does not affect ureteral motility.


The urinary excretion and serum concentration of calcium, magnesium, sodium and phosphate in male patients with recurring renal stone formation.

Only about 20% of renal stone cases have an unquestionable cause such as hyperparathyroidism, renal tubular acidosis etc. explaining their stone formation. About 20-40% are believed to result from idiopathic hypercalciuria. The purpose of the present investigation was to study the renal excretion of calcium, magnesium, sodium and phosphate in 47 consecutive men with recurring renal stone formation without a demonstrable underlining metabolic disease and, for comparison, 43 normal men. The results are related to previous hypotheses on renal stone formation. No difference in urinary calcium (either concentration or excretion) per day is found between the two groups. Consequently the concept of idiopathic hypercalciuria is questioned. The Mg/Ca ratio in urine is found lower in the stone patients than in the controls, suggesting that the Mg/Ca ratio might be of importance in stone formation.


Incidence, morbidity and complications of renal and ureteral calculi in a well defined geographical area.

In a well defined geographical area with only one hospital, the incidence of upper urinary tract stone was found to be 180 per 100 000 inhabitants, a figure not substantially higher than that reported more than 30 years ago. The male/female ratio was 3.6:1. The mean frequency of recurrence was 40% and the mean frequency of infection 12%. Hyperparathyroidism was found in 1.4% of all cases. Thirty-five per cent of the patients required hospital treatment and 19% needed operation. Renal pelvic stone was more common in the female (22%) than in the male (8.5%) patients. Spontaneous passage of stone occurred in 87.5% of the men and in 81.5% of the women. No seasonal variation in the onset of acute pain was demonstrable.


Renal function in experimental chronic hydronephrosis. I. Backflow studies with dextran.

By ligation of the ureter, causing partial ureteral stenosis, unilateral hydronephrosis was induced in 10 dogs. Renal function studies including creatine clearance and osmolality determination were performed both before and after the ureteral ligation. The renal function analysis after induction of hydronephrosis included pyelovenous and pyelolymphatic reflux studies, with deposition of dextran in the renal pelvis at different intrapelvic pressures. Analysis with respect to sodium, potassium, chloride and dextran in the thoracic duct lymph, peripheral blood and urine from the intact kidney were performed. The results show a reduction of the renal function in hydronephrosis, little transport of dextran via the lymph and blood, and no significant increase in the lymphatic transport of the studied ions on elevation of the intrapelvic pressure.


Renal function in experimental chronic hydronephrosis. II. Backflow studies with radionuclides.

Studies of backflow in experimental unilateral chronic hydronephrosis in dogs with a known residual renal function and renal pelvic volume were performed with radioactively labelled substances with molecular weights of ca. 600, 5 200 and 68 000 placed in the hydronephrotic renal pelvis. Three different pressure levels in the renal pelvis were used. Isotope concentrations were determined in the thoracic duct lymph, 0lood and urine from the contralateral kidney. The greater part of the test substances appeared to pass to the blood circulation, while a smaller part was found in the lymphatic ducts. The largest molecule, however, was only able to leave the renal pelvis to any appreciable extent at the highest pressure. In kidneys with a low grade of hydronephrosis and well preserved function, a relatively large amount of test substance left the renal pelvis (ca. 10-15%). In more advanced grades of hydronephrosis with greater impairment of renal function, the backflow was considerably less.


The relationship between hepatitis B antigen, e-antigen, and liver-pathology in patients treated with dialysis.

The relationship between hepatitis B antigen (HB Ag), e-antigen and liver pathology was studied in 27 patients who had died after regular dialysis treatment. The examination of the liver histology was done without knowledge of the history of the patient. Seventeen of the patients were HB Ag positive at death and had been carriers of the antigen for between 1 and 57 months. Two had chronic aggressive hepatitis and 10 chronic persistent hepatitis, but 5 had no histological signs of chronic hepatitis. e-antigen could be found in blood samples from all these patients. The cause of kidney disease, duration of dialysis and time of carriership of HB Ag showed the same variation among the patients without as among the patients with signs of chronic hepatitis. Two patients who had been HB Ag positive but were negative at death had no signs of chronic hepatitis. HB Ag positive samples available from one of these patients were also positive for e-antigen. Eight patients who were constantly negative for HB Ag were also negative for e-antigen. One of them had autopsy findings of a chronic persistent hepatitis. There were thus very moderate or even no histological signs of chronic hepatitis among these patients in spite of prolonged carriership of HB Ag. A very close correlation between HB Ag and e-antigen was also found.


Bladder papilloma in a child. Case report.

A case of bladder papilloma in a 12-year-old boy is presented. He had had painless, intermittent hematuria. An excretory urogram revealed a filling defect in the bladder. A walnut-sized, pedunculated papilloma was removed by transvesical extirpation. Histological examination showed a papillary bladder tumour, grade 1 (Bergkvist et al., 1965). Our patient also had a Cushing syndrome and later a bilateral adrenalectomy was done. The coexistence of two such rare conditions may not be purely coincidental. Control cystoscopies have shown no sign of tumoral recurrence.


Traumatic renal arteriovenous fistula treated by ligation and preservation of the kidney.

A case with traumatic renal arteriovenous fistula is presented. The diagnosis was established by selective renal angiography. The fistula was treated by ligation and division of the feeding artery. Postoperative angiography revealed complete closure of the fistula. The aetiology, clinical manifestations, diagnosis and treatment of renal arteriovenous fistula are discussed.


Arterial hypertension due to a renin-producing renal carcinoma.

The case history of a patient with arterial hypertension and increased plasma renin activity is reported. The causative pathology was found to be a renal carcinoma. After nephrectomy both blood pressure and plasma renin activity returned to normal.


Pulmonary gas exchange in asymptomatic smokers and nonsmokers.

Pulmonary gas exchange has been studied in 14 healthy smokers and 16 healthy nonsmokers (mean age: 36 years) breathing hypoxic, normoxic and hyperoxic gas mixtures, in a sitting position, at rest and on exercise. Alveolar-arterial oxygen tension difference is increased in smokers in hypoxia, at rest and on exercise, and the pulmonary diffusing capacity for oxygen is decreased. In normoxia the alveolar-arterial oxygen tension difference is increased on exercise. There is no difference between the two groups in hyperoxia. For the whole group there exists a negative relationship between (A-a)DO2 in normoxia and the diffusion indices measured on exercise. Arterio-alveolar carbon dioxide tension difference and the ratio physiological dead space/tidal volume are almost identical in both groups in any condition. A diffusion defect seems to be the more constant alteration of gas exchange in asymptomatic smokers.


Course and outcome of pregnancy in women with pulmonary tuberculosis.

Medical registrations of births in Norway during 1967 and 1968 were utilized in a study of the course and outcome of pregnancy in 542 women with pulmonary tuberculosis. A comparison with 112,530 pregnancies in women reporting no disease was made. Tuberculous women were found to have an excess of pregnancy complications, miscarriage, and labour difficulties. Their live births, however, were comparable with respect to gestation period, birth weight, morbid conditions and mortality to those of women reporting no disease.