[Preservation of dog limbs through hypothermic perfusion].

Different methods of preservation are examined in long-lasting extremity ischemia in dogs. After preservation of 10 h duration by hypothermia and perfusion the status of energy-rich phosphates and pH was equivalent to the status after 2 h of ischemia under control conditions.


[Pulmonary lipoprotein lipase activity after experimental bone fracture].

Five hours after a limited, nonhypotensive trauma without gross interference with coagulopathy the lung of dogs was found to be completely deficient of heparin-releasable, metabolically active lipoprotein lipase.


[Preventive treatment with methylprednisolone and heparin in experimental trauma and hemorrhagic shock].

Twenty-six anesthesized mongrel dogs were subjected to a standardized traumatic hemorrhagic shock. Compared with the control group prophylactic treatment with high doses of methylprednisolone reduced functional and histologic alterations of the lung. Methylprednisolone in combination with heparin pretreatment prevents microthrombi but produces more alveolar bleeding.


[Pulmonary hemodynamics, coagulation and morphological changes in the lung after thrombocyte aggregation inhibition and intravasal coagulation in experimental trauma and hemorrhagic shock].

26 mongrel dogs are subjected to a standardized bone trauma followed by a hypotonic hemorrhagic shock. Compared with a control and heparin group prophylactic treatment with Dipyridamol and Acetylsalicylic Acid decreases pulmonary vascular resistance significantly. After an initial period of hyperocagulability secondary fibrinolysis develops. The decrease of the fibrinogen level and the fall of total platelet count after trauma and hemorrhage can partly be prevented by the application of heparin, likewise the development of pulmonary microthrombosis. Histological examination shows a markedly diminished pulmonary microthrombosis.


[Prolonged survival of xenogeneic grafts after organ culture].

Organ culture of xenogeneic thyroids leads to a prolonged survival time. This effect can be reversed when donor-specific cells are injected at the time of transplantation. The results of this experiment disprove the assumption that target antigens are modulated or masked by organ culture.


[Behavior of intestinal motility and serum gastrin level after administration of prostaglandin A1, E1 and F2alpha in recent mechanical ileus of the rabbit].

In a mechanical ileus model in 70 rabbits, the effects of PGF2alpha-infusions, PGE1- and PGA1-injections on jejunal pressure and serum gastrin levels were studied. PGF2alpha increases, whereas PGE1 inhibits jejunal motility. PGA1 produces no significant response. A modulation of neurotransmission is discussed. The serum gastrin levels can be decreased by PGE1-injections, whereas PGA1 effects only small decreases. The importance of the vagal mechanism for the release of gastrin is emphasized.


[Effects of intraluminal pressure increase on oxygen consumption of the rabbit ileum and its possible pharmacological modification].

Elevated intraluminal pressure of rabbit small bowel induces a decrease of tissue pO2 of the bowel wall dependent on the applied pressure. After decompression local pO2 exceeds the initial pO2 values. While the i.v. application of 25 microgram/kg glucagon is not able to improve local oxygen supply of the distended bowel, local pO2 increases considerably after infusion of 7.5 ml/kg dextran 40. Decompression by operation or intestinal tube as well as application of dextran 40 are recommended in the treatment of ileus.


[Resuscitation with stroma-free hemoglobin solution after acute blood loss].

Resuscitation and volume replacement after acute blood loss is possible for a short duration by means of 6% stroma-free hemoglobin solution (SFH). Despite transcapillary loss of SFH, pulmonary edema is not provoked after massive infusion of cristalloid solution. The oxygen supply to the tissues is maintained by a compensatory rise in cardiac output and O2-extraction, mainly from the remaining red cell hemoglobin.


[Blood coagulation disorder, hemolysis and hypoalbuminemia after autotransfusion in experimental intraperitoneal hemorrhages].

Autotransfusion in a canine model (n = 15) causes anemia, thrombocytopenia, hypofibrinogenemia, hypalbuminemia, and metabolic acidosis and enhances elimination of intravenously injected 131I albumin. Contact of the shed blood with the peritoneal surface aggravates the pathologic findings; without simultaneous intraperitoneal heparinization the highest rates of hemolysis with concomitant oliguria were observed.


[Behavior of IgG, IgA and IgM in aseptic and septic postoperative processes].

After sterile surgical procedures, serum IgG, IgA and IgM concentrations again reach normal values at the 10th postop. day after initial lowering. During septicaemia this decrease is significantly more pronounced. By i.v. application of a high dose of human gammaglobulin normal values can be reestablished.


[Control of intensive care through the measurement of microcirculation and 02 consumption].

The pO2-multiwire electrode measures the intercapillary oxygen tension. The pO2 histogram, which results from such measurements gives precise information about the question as to whether microcirculation is disturbed or not. Thus, pathological changes in respiration and volume can be recognized earlier than with classical methods. The latter registers the mainly central variables which are compensated for a longer period of time. The local pO2 measurement allows individual regulation of respiratory therapy and monitors the response of oxygen therapy. Using this method oxygen deficiency as well as overdosage of oxygen supply can be averted. Thus, important diagnostic and therapeutic indications can be identified.


[25-OH-vitamin D in the serum of patients with femoral-neck fractures].

In 10 women with femoral neck fracture, 10 with fracture(s) evolved from accidents (mainly traffic accidents) and 10 without disease (controls) in January and July, the 25-OH-vitamin D levels in serum were measured by a competitive protein binding assay. Patients with femoral neck fractures exhibited significantly (p less than 0.05) lower 25-OH-vitamin D levels than the other groups. Additionally, in patients with femoral neck fractures calcium x phosphate product in serum was subnormal (below 25). In Germany, prophylactic dietary supplementation of vitamin D seems feasible.


[Criteria for the surgical treatment of hypothalamo-hypophyseal-dependent Cushing's syndrome].

This article offers criteria for the surgical treatment of pituitary-dependent Cushing's syndrome. Patients (n = 6) who showed no secondary complications of Cushing's disease underwent an implantation of 90Y and/or 192Ir into the pituitary gland. After implantation the excessive secretion of ACTH was suppressed to normal values and the symptoms of Cushing's syndrome disappeared. Following operation several patients received substitute therapy with other pituitary hormones. Fertility was not always conserved. Total adrenalectomy as alternative therapy was performed in adults with threatening symptoms of the disease (n = 4) and in children (n = 4). The symptoms of Cushing's syndrome disappeared. In two cases the development of a Nelson's tumor was observed. One was treated by implantation of 192Ir into the pituitary gland; the second needs no therapy up to now.


[Treatment of capillary hemangiomas and nevi flammei with light].

A report on the treatment of capillary hemangiomas and nevi flammei using laser or broad-band infrared light to initiate thermal coagulation in the blood-filled vascular spaces, leaving intact the nonaffected overlying skin layers. Clinical experiences with 26 patients treated with equipment developed by the group are discussed.


[Treatment of hepatic coma using extracorporeal perfusion with baboon and human liver as well as with activated charcoal].

In the 6 patients with hepatic coma hemoperfusions with 8 baboon and 2 human livers were carried out. Four awoke from the coma, one women could be discharged, but the others died of various complications and liver insufficiency. In the 4 patients with hepatic coma, 11 hemoperfusions with activated charcoal columns were performed. Two awoke from the coma, but they died of liver insufficiency. We were able to detect the elevation of preforming antibodies in a discharged patient.


Micro-organisms in the midgut of tsetse fly larvae.

Two types of micro-organisms were found in the midgut of Glossina morsitans larvae, a large Gram-negative bacterial rod and a small Gram-negative rickettsia-like micro-organism, although the occurrence of the rickettsial type is restricted. The location of these micro-organisms in a small area of the proventriculus of all three larval instars is discussed. The large micro-organisms resemble milk-gland bacteria, and further evidence is presented in support of a milk transmission hypothesis for these micro-organisms.


Studies on the bacteriophage PS8 of Agrobacterium tumefaciens (Smith and Townsend) Conn: physico-chemical properties of its DNA.

DNA from the bacteriophage PS8 was extracted and purified. The buoyant density was determined was 1.716 cm3/g. The guanine-cytosine content was calculated to be 57%. DNA molecules which looked like circles were found among linear strands in an electron-microscopic study. With an endonuclease from Streptomyces albus G the DNA was digested to 19 fragments, with molecular weights ranging from 600 to 7,400 daltons. The molecular weight of the DNA was determined to be 38.8 X 10(6) daltons +/- 8.7%.


Management and prognosis of gliomas of the optic pathways in children.

A follow-up study was made of 24 children with glioma of the optic pathways. In gliomas restricted to one optic nerve, total excision should be performed. The prognosis is excellent. Radiotherapy is not indicated. In gliomas of the anterior chiasm, a biopsy should be taken; occasionally, partial removal is indicated. The prognosis is good. Radiotherapy is indicated only if the follow-up shows a progression in the visual signs. In most cases, the growth of the tumor seems to be arrested. The vision remains stable and most patients have a useful degree of vision in at least one eye. In gliomas of the posterior chiasm with hypothalamic signs, the prognosis is poor. A biopsy and radiotherapy are indicated.


[Structural interpretation of a supposed symptomatic schizophrenia].

A short text spoken by a patient with a supposed symptomatic schizophrenia in lupus erythematodes is analyzed by means of a structural interpretation. While the text appears schizophrenic, it is only the confusion and intermingling of five quite distinct textual levels which create this impression. These five levels are presented in three distinctive modes of narrative. (1) Deviation and periphrase: while psychopathologically these breaks in the narrative are deviations from the main thread of argument, stylistically they are periphrasic statements, all having identical structures. They are all related emotionally as well as thematically to the central subject of the text. Their informational quality is impaired by their density and their interlocked form. (2) Narrative: the text contains three meaningful and well-arranged stories. In one case a multilevel narrative structure is employed. Each story represents a response to the initial question. (3) Metalanguage: on a metatextual level, the patient repeatedly makes reference to her linguistic peculiarities. These statements coincide with objective evaluation. Delusions and misidentification of individuals and situations used in classical psychopathological diagnosis can be given a different meaning (in the sense used by Weinrich) if interpretation has deepened the knowledge of the text. In this case, the similarity to schizophrenic texts is only superficial. A more detailed analysis illustrates the difference from schizophrenia on every level.


[Double suicide and symbiontic psychosis (suicide à deux and folie à deux)].

Symbiontic psychoses (induced delusions) are marked by 'solitude by twos'--together in alienation to the environment. This special psychological situation is dangerous and the foundation to develop 'suicides by twos' (double suicides). The relations between the psychotic partners (domination-subordination) change over to relations of double suicide (instogator-participant). The presuicide syndrome of such double suicides is described with two cases, one at the psychopathological borderline to a symbiontic psychosis, the other on the culmination of it (delusion of influence and reference).


Season of birth and Schneider-oriented diagnosis of affective disorder.

Most earlier studies and all recent studies on national samples have shown that compared with live births in the control population, schizophrenic patients have a significant excess of birth rates in the winter or early months of the year. In contrast, only some of the early research efforts and only some of the national studies (in England and Wales as well as for certain decades in Sweden) have demonstrated that the same holds true for patients with affective psychosis. The present German study, carried out on affective disorder diagnosed in a strongly Kurt Schneider-oriented clinic, found (as did most Scandinavian research on national samples) that there was no significant overrepresentation of births in the winter or early months of the year for all types of affective disorder, neurotic as well as psychotic. Thus, the findings on Schneider-diagnosed affective disturbances were similar to those on Schneider-diagnosed schizophrenia reported elsewhere.


Death anxiety in normal children and adolescents.

Instruments devised to measure death anxiety, depression, and manifest anxiety in adults were administered to 75 junior high-school students, 111 senior high-school students, and 38 adults in an effort ot determine the nature of any developmental differences among these groups. A number of significant differences were noted, with the senior high-school students showing greater anxiety, depression, and death anxiety than the other groups. These results are discussed in the context of tasks of adolescent development, and an item analysis of the death anziety questionnaire is presented. Developmental differences in the origin of death anxiety are related to previous studies of death anxiety in adults.


[Leukocyte count in manics, endogenous depressive, schizophrenics and neurotics].

Manic, endogenous depressive, schizophrenic and neurotic patients, 80 (40 females, 40 males) in each diagnostic group, are compared with regard to the white blood count with one another and with normal controls. Significant differences of means were found (1) between some groups of patients concerning the total number of leucocytes (micrometer +/- microseconds, micronD), the number of neutrophil granulocytes (micrometer +/- microsecond, micronN), the number of eosinophil granulocytes (micrometer +/- microseconds, micronD; micronN +/- microseconds, micronD) and the number of lymphocytes (micronN +/- micronD), and (2) between all groups of patients and normal controls concerning the number of monocytes (micronD, micronN, micrometer, microsecond +/- micronK). The findings are discussed.


Dynamics of contraction with special reference to calcium.

Using a new method for tetanizing frog ventricle muscle, the tension-length, force-load-velocity, and load-extension relations were determined under the steady active state. On the basis of these experiments a mechanochemical model was developed. Time courses of internal calcium concentrations, the rates of release, and uptake of calcium during isometric twitches were calculated by the model.


Isometric dynamic response of mammalian heart muscle due to step changes in the calcium concentration of the perfusing medium.

The isometric tension transient response of isolated kitten papillary muscle was found to exhibit direction-dependent dynamics when subjected to step changes in the calcium concentration of the bathing medium. The tension transient curves could be resolved into a minimum of two to three exponential components, which could be considered to indicate different calcium compounds or compartments within the muscle. However, a model relating calcium diffusion across the muscle to the dose-response curve indicates that the exponential components of the tension transient curves are due to the properties of calcium diffusion through the extracellular space, and that the direction-dependent dynamics are caused by the nonlinearity of the dose-response curve.


Contraction duration and diastolic stiffness in aged canine left ventricle.

The data obtained from groups of young and old beagles demonstrate that senescent beagle hearts are characterized by lower contractile function as measured by developed pressure and maximal rate of pressure change with time, by longer contraction duration, and by increased dynamic stiffness per given pressure as measured by the sinusoidal forcing technique.


Delay in diastolic restitution of full myocardial contractility in guinea pig atrium.

In an isolated perfused left atrium of guinea pig, pressure amplitudes were recorded at 37 degrees C and a stimulation rate of 240/min with interposed variable resting pauses. After prolonged intervals the preparation develops maximum pressure, which does not depend on perfusion time or on any positive inotropic intervention. The latter is found to shorten the time needed for restitution of full contractility. Nifedipine (5 X 10(-7)M) exerts its negative inotropic effect mainly by a delay in restitution time; acetylcholine (2 X 10(-7)M), by a concomitant reduction of all pressure amplitudes over the whole range of stimulus intervals. The latter effect is similar to that of lowering [Ca2+]o.


Interaction of lanthanides with muscle microsomes.

The interaction of gadolinium, a lanthanide with calcium-blocking action, with isolated muscle microsomes has been studied. Two classes of binding sites were present, 80 and in excess of 300 nmol/mg in number, respectively. Divalent cation, including Ca, Zn, and Cd, blocked the higher affinity site. Antibiotic ionophores X537A and A23187 enhanced binding, with positive cooperativity. ATP enhanced binding at low concentration (10-20 muM) of nucleotide, and without ATP-hydrolysis. The data suggest a dissociation in the intact membrane between the binding and ATP-hydrolytic portion of the transport site.


Voltage-clamp experiments by double microelectrode technique in rabbit sinoatrial node cell.

When a man-made strand of the rabbit sinoatrial node (S-A node) was shortened by ligation, the spatial decay of the electrotonic potential decreased and the input impedance increased. A satisfactory voltage clamp was achieved in the small S-A node specimen using the double microelectrode technique (Deck, Kern, and Trautwein, 1964).


A new spectroscopic approach to cardiac energy metabolism.

The optical characteristics of the hemoglobin-free perfused rat heart have been examined in detail. For dual-wavelength spectrophotometry, absorption pairs at 605-620 nm and 587-620 nm are found to be suited for the investigation of the oxidation-reduction changes of cytochrome aa3 and oxygenation-deoxygenation of myoglobin in cardiac tissue. Techniques by which the absorption changes of myoglobin and cytochrome aa3 can be measured during one cycle of contraction-relaxation are presented. The results demonstrate that, in the aerobic state, myoglobin is more oxygenated during the systolic and diastolic periods and deoxygenated in the resting period, whereas cytochrome aa3 is more reduced in the systole and diastole and oxidized in the resting period.


Role of slow inward current on premature excitation in ventricular muscle.

Action potential durations in premature excitations showed paradoxical prolongation at the shorter coupling intervals; this was abolished by manganous ions. Voltage-clamp experiments also disclosed a transient increase of slow inward current in premature excitations. These results indicate that prolongation of action potential durations was mainly brought about by changes in slow inward current, especially in its characteristics of recovery from inactivation.


Significance of heat loss in energetics of left ventricle.

Left ventricular heat loss was examined by measuring the temperatures in the coronary sinus blood, in the aortic blood, and in the left atrial blood by thermistors. The temperature was highest in the coronary sinus blood, in the aortic blood next, and it was the least in the left atrial blood. However, since the aortic blood flow was naturally higher than the coronary sinus blood flow, the heat loss was larger in the left ventricular cavity than in the rest of the chambers. This heat loss was mostly proportional to the magnitude of the changes of both the arterial blood pressure and the aortic blood flow.


Myocardial adenine nucleotides after infusion of adenosine.

In the rabbit heart, continuous infusion (12 ml/hr) of 1% adenosine into the superior caval vein, or of 0.5% adenosine into the left myocardial ventricle, for a period of 3 hr increased the myocardial tissue level of ATP by almost 40% over the control (5.0 mumol/g). Both shorter or longer periods of application and lower or higher concentrations of adenosine, as well as the infusion of adenosine into the left atrium, were less effective. The increase markedly outlasted the period of application of adenosine. It did not result from the adenosine-induced systemic hypotension and decrease in cardiac work, but must be attributed to a direct metabolic effect of the adenosine infusion.


Transmural mitochondrial differences in myocardium.

Two functional mitochondrial populations with different sedimentation rates (S) were obtained from homogenates of canine myocardium by rate zonal centrifugation using an iso-osmotic Ficoll gradient. To ascertain the origin of these populations, the left ventricular wall of normal myocardium was divided into subepicardial (outer one-third), intermediate (middle on-third), and subendocardial (inner one-third) layers. The slow S mitochondria comprised 75% of the mitochondrial population of the subepicardial layer. In contrast, the fast S mitochondria contributed 65% of the subendocardial population. Intermediate layer mitochondria resembled those of the subepicardium. Mitochondria isolated from the three layers had approximately the same density, as shown by isopycnic zonal centrifugation. These studies indicate that mitochondria from subepicardial and subendocardial layers of normal myocardium differ in size and shape but not in density. Electron micrographs (EM) of the subepicardium showed many mitochondria as long as 4 to 8 sarcomeres. Mitochondria from the outer and inner layers of normal myocardium had the same oxidative phosphorylation parameters. Acute myocardial infarction, lasting 1 or 2 hr, resulted in the selective loss of the fast S mitochondria. Because the fast S mitochondria are prevalent in the subendocardium, these results may explain the greater vulnerability of this layer to anoxia.


Uptake and release of immunoreactive insulin in coronary circulation in man: studies at rest, during exercise, and during glucose and insulin infusions.

Significant uptake and release of immunoreactive insulin by the heart have been observed in man, and this is related to plasma insulin levels. Exercise and the fed state appear to affect the myocardial handling of insulin. The findings could not be related to myocardial carbohydrate metabolism, but could, during exercise, be related to myocardial lipid metabolism.


Influence of carbocromene on free fatty acid metabolism of the heart.

In view of the fact that carbocromene (C) influences the metabolic processes in the heart muscle, its effect on the transport of substrates into the heart tissue was investigated. In rat heart slices C inhibits the uptake of [1-14C]palmitic acid up to 40%, while 14CO2 production is reduced to the same extent. At the same time oxygen consumption diminished by about 20%. Using 3-O-[14C] methyl-D-glucose as metabolic marker it was shown that the uptake of glucose into the heart tissue increased by 30% under the influence of C. From these results it can be concluded that C inhibits the oxidation of FFA in favor of glucose and diminishes the oxygen-wasting effect of FFA.


Metabolism of individual fatty acids in heart muscle.

We have studied the incorporation of various long chain fatty acids into tissue lipids using various heart preparations. We found that individual fatty acids are incorporated into various lipid fractions at unequal rates. In particular, erucic acid was shown to be a poor acyl donor for various acylation reactions. Labeling of triacylglycerol by exogenous fatty acid was found to be extremely rapid in the perfused rat heart and in the in vivo heart.


Myocardial fatty acid and cardiac performance.

Isoproterenol enhanced myocardial triglyceride utilization and incorporation of exogenous fatty acid into triglyceride fraction in the perfused rat heart in the presence of glucose. However, in the absence of glucose, cardiac performance was considerably aggravated by isoproterenol. This suggests that glucose might be an essential fuel in the heart stimulated by isoproterenol.


Effects of hypoxia and digitalis glycosides on myocardial stiffness.

The influences of hypoxia and of the interactions of hypoxia with digoxin and ouabain on myocardial stiffness were studied at two extracellular calcium concentrations (2.5 mM and 4.0 mM) in isolated, isometrically contracting cat papillary muscles. Stiffness (delta T/delta L), defined as a change in tension (delta T) in response to an imposed length change (delta L), was measured during contraction and during rest by use of a sinusoidal forcing function. Neither digoxin, ouabain, nor increased extracellular calcium altered contraction or resting stiffness in the well-oxygenated environment. Resting stiffness was increased at the end of hypoxia only in the presence of digoxin in both 2.5 mM and 4.0 mM Ca. Contraction stiffness was increased in 2.5 mM Ca by hypoxia alone and by hypoxia in the presence of digoxin or ouabain, but was not increased in experiments carried out in 4.0 mM Ca. Thus it appears that hypoxia per se increases contraction stiffness, but increasing extracellular calcium from 2.5 mM to 4.0 mM prevents the increase elicited by hypoxia; resting stiffness, however, is increased by hypoxia only in the presence of digoxin, and this occurs in both 2.5 mM and 4.0 mM Ca.


Effect of diltiazem on calcium- and noradrenaline-induced contractions in isolated rabbit aorta.

The effect of diltiazem on calcium- and noradrenaline-induced contractions was investigated in the K-depolarized aortic strip of the rabbit. Diltiazem inhibited the contraction induced by calcium ions dose-dependently. A lower concentration of diltiazem produced no significant influence on the contraction induced by noradrenaline, while a higher concentration suppressed it. It is assumed that in the rabbit aorta diltiazem effectively inhibits the contraction mediated by the influx of calcium ions but it is less effective with the contraction induced by the release of sequestered calcium.


Free fatty acid content of myocardial interstitial spaces of dog.

Morphological and biochemical observations from our laboratory have shown the presence of lipids in the cardiac interstitial spaces of the dog. The present study was designed to assess the importance of free fatty acids (FFA) in these lipids using FFA or sucrose tracers in 14 anesthetized fasting open-chest mongrel dogs. Endogenous FFA and labeled tracers were measured in arterial and coronary sinus plasma; they were also determined in lymph collected from cardiac efferent lymphatic trunks. [14C] sucrose was infused at a constant rate in the femoral vein of 5 dogs. The concentration of the tracer in the lymph was 90% of the arterial concentration after 60 min of infusion. On the other hand, when [1-14C] palmitate was infused at the same rate in 7 dogs, the ratio of lymph to arterial tracer concentration was only 20% (60 min) and 25% (120 min), even though the myocardial extraction and oxidation of the tracer were stable. This ratio tended to reach a plateau (greater than or equal to 90%) only 24 hr after a bolus injection of the tracer. This tracer study shows the presence of a pool of myocardial fatty acids with a relatively slow turnover rate that may constitute an important reservoir of FFA.


Electrically induced automaticity in canine ventricular myocardium.

Repetitive spontaneous action potentials (SAP) could be induced in canine ventricular and atrial muscle, although this inhibitory action was antagonized by the pretreatment with voltage range between about -60 mV and 0 mV. The SAP seemed dependent on both slow inward Ca2+ and Na+ currents and was suppressed by verapamil, Mn2+, and diltiazem, but not by tetrodotoxin. The increase of extracellular potassium concentration also suppressed the SAP. Acetylcholine could not block the SAP in ventricular muscle, but inhibited that in atrial muscle, although this inhibitory action was antagonized by the pretreatment with atropine. The automatic activity was attributed to slow inward Ca2+ and Na+ currents modified by decreasing time-dependent K+ outward current and K+ anomalous rectification.


Effects of insulin on mammalian cardiac muscle.

Insulin increases the contractile force of myocardium with hyperpolarization and a faster rate of fall of the action-potential plateau. This phenomenon is augmented inthe reduced-K+ or ouabain solution. It is suggested that the insulin-induced positive inotropism can be explained by facilitation of inward movement of Ca2+, which possibly is associated with an increase in outward movement of K+.


Inotropic and chronotropic effects of antiarrhythmic agents onisolated blood-perfused canine ventricular tissue.

In the isolated blood-perfused canine ventricular tissue, antiarrhythmic agents could be classified as having: 1) positive chronotropic and inotropic effects (procainamide), 2) negative chronotropic but positive inotropic effects (quinidine), and 3) negative chronotropic and inotropic effects (lidocaine, ajmaline, diphenylhydantoin, and propranolol).


Influence of quinidine on ATP-linked calcium binding by heart mitochondria and microsomes.

The action of quinidine on heart microsomal and mitochondrial calcium binding in the presence of MgATP was studied under different experimental conditions and compared with other antiarrhythmic agents such as procaine amide and lidocaine. Quinidine stimulated microsomal calcium binding but depressed mitochondrial calcium binding. Although procaine amide stimulated microsomal calcium binding, it did not affect mitochondrial calcium binding. On the other hand, lidocaine depressed calcium binding by mitochondria without affecting calcium binding by the microsomal fraction. The stimulation of microsomal calcium binding by quinidine was not apparent at high concentrations of Mg2+, low concentrations of ATP, or low concentrations of Ca2+. The depressant action of quinidine on mitochondrial calcium binding was not observed at low concentrations of Mg2+ or ATP but was more pronounced at low concentrations of Ca2+. These results suggest that the action of quinidine on mitochondria may play a major role in eliciting cardiodepressant effect.


Effects of morphine and halothane on canine cardiac function before and after cardiopulmonary bypass.

In an effort to compare the effects of anesthetics on cardiac functions and metabolism, mongrel dogs were anesthetized with morphine (3 mg/kg, N2O 50% in oxygen) or halothane (0.7%, N2O 50% in oxygen). Hb, Ht, pO2, pCO2, pH, O2 content, lactate, and pyruvate in the arterial and coronary sinus blood were measured and ECG, LVP, CVP, AP, and CO were recorded. Aorta was cross-clamped for 30 min under cardiopulmonary bypass (CPB). Hemodynamic and metabolic survey were continued until 120 min of recovery period. Results were as follows: Hemodynamics, such as LVP, AP, and CO, were depressed after CPB, then gradually returned to control level. Subendocardial ischemia observed through ST depression and QRS widening on ECG, as well as DPTI/TTI ratio under 1.0, disappeared in the recovery period. Lactate was produced by the heart after anoxic arrest and was extracted at 120 min after CPB. Halothane and morphine did not show any significant differences of effects on cardiac function and metabolism in this study.


Effects of halothane anesthesia on myocardial contractility, coronary as well as systemic hemodynamics, and myocardial metabolism in dogs.

Halothane depressed coronary and other systemic circulations as arterial halothane concentration rose in dogs. Myocardial oxygen consumption decreased as the cardiac action, especially "myocardial contractility", was depressed, while the whole-body oxygen usage remained steady. Lactate and pyruvate levels in arterial, mixed venous, and coronary venous blood did not show any signs of tissue hypoxia or development of anaerobic metabolism even in very deep halothane anesthesia. Coronary blood flow seemed well maintained for the demand, and changed almost in parallel with the myocardial oxygen consumption during the observation.


Relationship between energy liberation and utilization in ischemic cardiac muscle.

Mitochondrial respiration, succinate dehydrogenase coenzyme Q reductase, and myosin B were investigated in ischemic myocardium from experimental myocardial infarction in dogs. Respiratory control ratio of mitochondria was impaired by ischemia at 60 min after coronary ligation, and oxygen consumption was inhibited 120 min later. Enzyme activity of succinate dehydrogenase coenzyme Q reductase was decreased at 6 hr after coronary ligation. Calcium ion sensitivity of myosin B declined 12 hr after coronary ligation. However, adenosine triphosphatase activity of myosin A from infarcted myocardium was not different from that of the intact one. These results suggest that interaction in the sequence of enzyme complexes was first impaired in ischemic myocardium and that deterioration of enzyme activity was then manifested.


Glycolytic ATP and its production during ischemia in isolated Langendorff-perfused rat hearts.

The perfused rat heart was used to assess the possible contribution of glycolytically produced ATP to the maintenance of the action potential in the normoxic heart, and to the maintenance of membrane integrity in the underperfused, ischemic heart. During normoxia, pyruvate (10 mM) was nearly as able as glucose (10 mM) to maintain the normal action potential. During ischemia (reduction of perfusion pressure of Langerdorff heart from 100 to 20 cm H2O), total tissue values of ATP and creatine phosphate were similar in pyruvate and in glucose hearts. However, pyruvate-perfused hearts had higher tissue levels of cyclic AMP during the ischemic period, and during the reperfusion period they had an increased release of lactate dehydrogenase and an increased incidence of arrhythmias when compared with glucose hearts. It is proposed that these differences can be related to a higher rate of production of glycolytic ATP. The anatomical, biochemical, and pharmacological evidence favoring a cytoplasmic compartment of ATP located in relation to the cell membrane is reviewed.


An experimental study of the effect of glucose-insulin-potassium solution on energy metabolism of infarcted cardiac muscle.

The effect of GIK (glucose-insulin-potassium) infusion on the energy liberation of the infarcted heart muscle was studied experimentally in relation to epicardial electrocardiographic changes and cardiac dynamics. In the case of 30-min coronary ligation, the spread of the zone showing ST segment elevation was not depressed significantly, but the mean voltage values of ST elevations were suppressed in the peri-infarcted area, and the uncoupling of oxidative phosphorylation in the peri-infarcted area was also obscured by the GIK treatment. Cardiac dynamics did not change with GIK treatment. On the other hand, in the 60-min coronary ligation, the spread of the zone showing ST segment elevation was reduced significantly and the negative inotropism induced by coronary ligation was suppressed with GIK infusion. However, the uncoupling of oxidative phosphorylation in the infarcted area and in the peri-infarcted area did not show any significant improvement. Therefore, the disturbed energy metabolism of the peri-infarcted area of 30-min ligation might be improved by the effect of GIK infusion. These data suggested that the GIK infusion improved the energy liberation of the so-called twilight zone at 30 min after ligation, and then reduced the genuine infarcted zone after 60 min of ligation.


Chronotropic effects of calcium and magnesium ions at different temperatures.

In the isolated right atrium of rabbit hearts, excess calcium causes an increase of heart rate at 38 degrees C; this effect is absent or even reversed at a temperature of 30 degrees C. From microelectrode studies it seems that when the calcium concentration is increased the pacemaker shifts within the sinoatrial node to cells in which excess calcium causes an acceleration of diastolic depolarization (type A). In fibers where the impulse originates at low calcium (type B), excess calcium causes a deceleration of diastolic depolarization. At low temperature, the effects on type A fibers are completely absent. Excess magnesium has a negative chronotropic effect at both temperatures, mainly by a deceleration of diastolic depolarization in type B fibers.


Effect of xanthine oxidase inhibitor on myocardial ischemia.

The xanthine oxidase inhibitor, 4-hydroxypyrazolo(3,4-d) pyrimidine (HPP), Allopurinol, caused augmentation of myocardial uptake of [3H] hypoxanthine, which was eventually completely incorporated into ATP. The decrease of [32P] orthophosphate incorporation into ATP induced by isoproterenol was restored by HPP administration.


Alteration in calcium metabolism in mitochondria isolated from ischemic and reperfused myocardium.

This study determines the effect of ischemia and reperfusion on energy-linked Ca2+ uptake by myocardial mitochondria. The left anterior descending coronary artery was occluded in 14 mature pigs for 2 hr. In seven animals the ligature was released and the ischemic zone reperfused for 2 additional hours. After sacrifice, mitochondrial function was measured in normal and reperfused or ischemic areas of the left ventricle, using a polarographic method. Mitochondria were prepared without EDTA by standard procedures and Ca2+ uptake measured by 45Ca2+ isotope tracer. Uptake of Ca2+ by mitochondria derived from ischemic myocardium is markedly impaired with or without phosphate. Reperfusion may accentuate this impairment. The presence of exogenous Ca2+ inhibits the ability of ischemic or reperfused mitochondria to phosphorylate ADP.


Influence of ATP or oxygen plus substrate on occurrence of the calcium paradox.

Reperfusion of Ca2+-deprived rat hearts with Ca2+-containing medium results in irreversible cell damage (calcium paradox). In this study this type of cell damage was studied in the anoxic rat heart, in the presence and absence of glucose. Creatine kinase (CK) release was used to define cell damage. Hearts were perfused successively with Ca2+-containing medium (30 min), Ca2+-free medium (5 min), and Ca2+-containing medium (5 min). In the presence of glucose, myocardial ATP was maintained at a fairly high concentration. Reperfusion with Ca2+ resulted in an immediate and massive release of CK. In the absence of glucose, the ATP concentration was almost zero after 30 min. Reperfusion with Ca2+ did not result in release of CK. Massive release occurred as soon as these hearts were reoxygenated. It is concluded that this type of calcium-induced cell damage only occurs in the presence of ATP, or oxygen plus substrate. Mitochondria most likely play a major role in the occurrence of the calcium paradox because of their ability to accumulate huge amounts of Ca2+ under these conditions.


Calcium paradox: changes in high-energy phosphate compounds of isolated perfused rat hearts.

When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. A possible mechanism for the origin of myocardial necrosis, caused by intracellular Ca2+ overload, is discussed.


Role of myocardial lipids in development of cardiac necrosis.

Significant alterations in fatty acyl composition of cardiac phospholipids and neutral lipids are induced by dietary cod liver oil in the rat. Increased dietary availability of docosahexaenoic acid (22:6 omega3) leads to extensive replacement of linoleic acid (18:2omega6) and arachidonic acid (20:4omega6) in phospholipids. Dietary cod liver oil (10%) reduces isoproterenol stress tolerance and results in increased development of cardiac necrosis and mortality following isoproterenol treatment. It is suggested that diminished catecholamine stress tolerance may be related to altered synthesis of prostaglandins or related products.


Energy liberation in abnormal cardiac muscle.

Uncoupling of oxidative phosphorylation was suggested in experiments using the infarcted myocardium, even in dogs with 15-min ligation. The same type of disturbance in mitochondrial respiration was observed in dogs with reperfusion after 45-min ligation, whereas the disturbance was recovered in dogs with reperfusion after 15-min ligation.


Disturbance of myocardial energy liberation in experimental charcoal embolism of canine pulmonary artery.

Experimental charcoal embolism of the pulmonary artery was produced in dogs. Changes in hemodynamics, electrophysiology, and cardiac energy liberation were observed. The effects of histaminic and antihistaminic drugs on these changes were also studied. After two infusions of charcoal suspension, acute right ventricular overloading was recognized hemodynamically and electrophysiologically. Mitochondria isolated from both ventricles exhibited uncoupling of oxidative phosphorylation polarographically. These changes were enhanced with histamine injection and reduced with diphenhydramine injection. Histamine was seen to have some uncoupling effects on the heart mitochondria and a slight effect on cardiac dynamics. It is concluded that oxidative phosphorylation of the heart mitochondria was uncoupled in the acute stage of experimental pulmonary embolism, and that histamine might emphasize this change directly or indirectly or both, that is, directly affecting the myocardial cell metabolism, and indirectly aggravating myocardial hypoxia through pulmonary vasoconstrictive action.


Stopping of spontaneous beating of cultured mouse and rat myocardial cells by a toxin (thermostable direct hemolysin) from Vibrio parahaemolyticus.

Low concentrations of thermostable direct hemolysin from Vibrio parahaemolyticus stopped the spontaneous beating of cultured mouse and rat myocardial cells. These low concentrations depolarized the maximal diastolic potential and inhibited the generation of action potential of cultured myocardial cells. The toxin lost its activity when preincubated with ganglioside, GT1 or GM1. GT1 was more effective than GM1. High concentrations of the toxin caused morphological damage of cultured mouse and rat myocardial cells, but did not stop the beating, or cause morphological damage of cultured chick myocardial cells.


Contribution of an electrogenic sodium pump to the response of sinoatrial node cells to acetylcholine.

ACh (10-7) - 10(-6) g/ml) induced hyperpolarization in pacemaker cells in the sinoatrial (SA) node of the rabbit heart varied inversely with the level of the maximal diastolic potential of the pacemaker cells. The hyperpolarization induced by ACh was completely abolished at 4 degrees -6 degrees C. Ouabain (10(-6) g/ml) markedly depressed or abolished the hyperpolarizing response. The response was also depressed in K-free solution, but not abolished. In Ca-free or low-Na solution, the sino atrial node cell responded well to ACh, showing marked hyperpolarization. Present results indicate that the hyperpolarization induced by ACh is at least in part due to an electrogenic Na pump activated by ACh.


Increase in membrane conductance and positive inotropic action of hemolysin produced by Vibrio parahaemolyticus on rabbit myocardium.

The effects of purified thermostable direct hemolysin from the cultured filtrate of Vibrio parahaemolyticus on both S-A node cells and atrial cells were studied electrophysiologically. Hemolysin caused the membrane conductance to increase, thereby causing membrane depolarization. The major ion responsible for this depolarization was Na+, but other ions, such as K+ and Ca2+, also participated. Positive inotropic action of hemolysin was observed, and the Na-Ca exchange mechanism was enhanced after hemolysin treatment.


Effects of anoxia and metabolic inhibitors on reaction of the fast sodium system.

The effects of anoxia and metabolic inhibitors on inactivation and reactivation of the fast Na system of dog ventricular muscle fibers were studied by examining (dV/dt)max of the action potential upstroke. Anoxia for 60 min, dinitrophenol (DNP) (2.0 mM), and sodium azide (2.0 mM) depressed markedly steady-state (dV/dt)max at each membrane potential produced by changing [K]o. Anoxia tended to prolong recovery slightly, but DNP and azide changed little the time course of recovery of the (dV/dt)max, which was studied by applying double pulses to elicit action potential at different intervals. It is concluded that anoxia, DNP, and azide caused prominent depression of the maximum Na conductance but had less influence on its recovery kinetics.


Intraventricular conduction disturbance due to delayed recovery from ventricular inactivation in chlorpromazine-treated dogs.

In in situ canine hearts, chlorpromazine induced a time (preceding cycle length)-dependent decrease in conduction velocity within the ventricle. Thus, QRS duration of nonpremature beats was lengthened at rapid pacing rates while QRS duration of atrial premature beats was lengthened at short coupling intervals. These slow conductions were not due to reduced take-off potential of ventricular action potentials but to drug-induced slow recovery of the rapid Na+ system. The phenomenon may be responsible for reported QRS prolongation and fatal ventricular arrhythmias encountered in patients receiving phenothiazines.


Factors accounting for growth and atrophy of the heart.

Growth of the rat heart was induced by intrathoracic aortic banding, while atrophy followed hypophysectomy. During the early phase of hypertrophy, RNA concentration increased markedly. During the period of atrophy, RNA concentration was reduced. These changes in RNA concentration seemed to account for either the increased or the decreased rates of protein synthesis that was observed during hypertrophy or atrophy, respectively. Rates of protein degradation were unaffected during changes in heart size. These findings suggest that alterations in synthesis, processing, or degradation of RNA play a key role in modification of heart size.


Effect of low protein diet on cardiac function and ultrastructure of spontaneously hypertensive rats loaded with sodium chloride.

The effects of low protein diet on cardiac metabolic and structural changes subsequent to an extremely high pressure load were investigated. Spontaneously hypertensive rats(SHR) were divided into four groups, and fed the following diets for four weeks: 1) Group A: regular diet (23% protein) and water, 2) Group B: regular diet and 1% saline, 3) Group C: low protein diet (10% protein) and water, and 4) Group D: low protein diet and 1% saline. Two weeks after the start of feeding, there was no significant difference in the left ventricular ultrastructures between the corresponding regular and low protein diet groups. Four weeks after, degenerative findings such as streaming of Z lines, dilatations of smooth endoplasmic reticulum, and disarrangements of myofilaments appeared Group D, while in Group B electron microscopic findings indicated hypertrophy. Incorporation of [14C] leucine into the myocardial myosin B in Group D was significantly low, with a resulting fall of the LVdP/dtmax per integrated isometric pressure (IIP) and a rise of the left ventricular end-diastolic pressure (LVEDP), as compared to that in Group C at four weeks after the start of feeding. These observations suggest that, in the heart with an extremely high pressure load, low protein diet hinders the development of hypertrophy to the load with resulting heart failure.


Ischemic-like change produced in canine heart by atractyloside: a chemical model.

Experiments were conducted in two canine models. Intracoronary infusion of atractyloside resulted in physiological, biochemical, and ultrastructural changes similar to those seen with ischemia. The fact that atractyloside, a specific inhibitor of adenine nucleotide translocase produces this change in vivo suggests that this inhibition in the key disturbance that initiates the metabolic derangements seen with ischemia. This chemical model seems to provide unique opportunities to study the possible factors that may reverse adenine nucleotide translocase inhibition and thus possibly prevent cell injury.


Effects of acetate on myocardial contractility and epicardial ECG of isolated and perfused feline hearts.

In isolated, perfused hearts, the effects of acetate on epicardial ECG and ventricular pressure were observed during various times of perfusion. Anions-Cl-and acetate-caused changes of ECG configuration, especially in the ST segments. These were different in Phase I (fast compartment) and Phase II (slow compartment).


Species difference of mitochondrial respiration in experimentally induced heart failure.

In guinea pigs with acute heart failure, a decrease in oxygen consumption (QO2) at state 3 and an increase in QO2 at state 4 were seen and the respiratory control index (RCI) was markedly lowered; ADP/O ratio was not affected. In rabbits with acute heart failure, both RCI and ADP/O ratio showed a statistically significant decrease. In dogs with acute and chronic heart failure, no impairment of respiratory function of mitochondria was seen. These conflicting results may be attributed to the difference in experimental conditions, namely, the species difference and the difference in methods to produce experimental heart failure. With special regard to species difference, it was confirmed that the RCI of myocardial mitochondria of healthy dogs was much lower than that of healthy guinea pigs. It is suggested that the difficulty of obtaining intact mitochondria may be responsible for the species difference in experimentally induced heart failure.


Experimental studies on the effect of glucocorticoids on cardiac muscle.

Abnormal electrocardiographic changes were found in some patients on long-term glucocorticoid treatment. In experimental animals, chronic glucocorticoid administration resulted in an increase of amplitude of the QRS complex and abnormal ST and T changes. Changes of action potential were somewhat different in the subendocardial and the subepicardial layers. Diffuse mitochondrial alterations were found, particularly in the subepicardial layer. In rabbits treated with glucocorticoids, no significant changes were found in either serum or myocardial potassium content. Slightly decreased Vmax was the observed hemodynamic change.


Transmural gradients in myocardial gas tensions in regionally ischemic canine left ventricle.

Previous studies from this laboratory have demonstrated the usefulness of myocardial gas tensions as measured by mass spectrometry for the quantitative assessment of regional myocardial ischemia (Khuri et al., 1975a). Progressive increases in myocardial carbon dioxide tensions were noted when progressive reduction in coronary blood flow was created by means of a variable constrictor. The present study was designed to determine if changes in myocardial oxygen and carbon dioxide tension were greater in deep, compared to more superficial, myocardial layers. In eight anesthetized dogs, progressive reduction in circumflex coronary flow was associated with a progressive reduction in myocardial oxygen tension and a progressive increase in myocardial carbon dioxide tension and intramyocardial ST-segment voltage. Evidence of a transmural gradient in the severity of ischemia was present at all degrees of flow reduction. These results confirm the findings of previous metabolic studies, which demonstrated gradients in lactate and high-energy phosphates. Myocardial carbon dioxide tension, which can be monitored continuously by mass spectrometry, would appear to provide a useful means of quantitatively assessing changes in regional myocardial metabolism.


Local pulsatile intramyocardial pressure (IMP) as a vector force: simultaneous measurements of IMP and tissue oxygen availability.

A directional nonuniformity of the intramyocardial pressure (IMP) was observed in anesthetized open-chest dogs using a piezoelectric pressure sensor implanted in the left ventricular myocardium. The nonuniformity seemed to be attributable to the variation in myocardial fiber orientation. The IMP, which developed in a direction parallel to the base-apex line, was measured in the deep portion of the myocardium, simultaneously with local O2 availability. In some cases, IMP decreased quickly as soon as a decrement in O2 availability had proceeded only slightly as a result of ligation of the anterior descending artery (LAD). In other cases, the once decreased IMP recovered gradually even when O2 availability remained lowered by continuation of the ligation. These observations indicated that IMP had no direct dependency on O2 availability in the case of acute LAD.


Hemodynamic and metabolic changes caused by regional ischemia in porcine heart.

Myocardial ischemia was induced in the pig by reducing the left anterior descending coronary artery (LAD) flow to 26% of its control value. After one hour, the LAD was reperfused for 50 minutes. During ischemia and reperfusion, cardiac output correlated strongly with arterial levels of lactate and nucleosides (all r less than - 0.85). Myocardial inosine production seems to be a good marker of ischemia because it correlated very well with myocardial lactate production (r = 0.99).


Cardiac muscle taurine: effects of acute left ventricular ischemia in the dog and anoxic perfusion of the rat heart.

It has been proposed that taurine, or one of its metabolites, may exert anti-arrhythmic effects in cardiac muscle. The present studies examined the effects of acute left ventricular ischemia in the dog (in vivo) and whole heart anoxia in the perfused rat heart (in vitro) on the content and distribution of taurine. In control dogs an increasing outer-to-inner gradient in taurine content was observed in the left ventricle. Left circumflex artery ligation for four hours markedly decreased tissue taurine content, the greatest disappearance occurring in the inner zone. Anoxic perfusion resulted in a similar decrease in rat ventricular taurine levels. Recovery of taurine in the heart perfusates indicated that tissue disappearance, secondary to oxygen deficiency, involved leakage into the extracellular fluid rather than metabolic conversion.


X-ray microanalysis of mitochondrial calcium.

X-ray microanalytical techniques using wavelength dispersive (WDS) and energy dispersive spectrometry (EDS) indicate that Ca2+ is present in intramitochondrial granules which occur in myocardial cells following irreversible ischemic injury. Preliminary results using tissue prepared for routine electron microscopy suggest that the degree of calcium binding that occurs in the mitochondria increases with increased duration of ischemia. Free ions are leached out of the tissue during processing; hence, the role of ion redistribution in producing myocardial necrosis cannot be elicited from a study of this nature. However, with continued progress in the development of techniques of tissue preparation x-ray spectrometry may provide a means of assessing quantitative ion alterations that occur during ischemia.


Coronary circulation, myocardial metabolism and hemodynamics of pacing-induced angina.

The following changes were noted during pacing-induced angina: The coronary sinus blood flow was less than it was during the control period and less than that in the myocardial ischemic group without induced angina. While myocardial oxygen consumption did not increase, myocardial metabolism became anaerobic. The possibility of myocardial dysfunction also was noted.


Metabolic consequences of Sephadex-induced reduction of coronary flow in isolated rat heart.

With a polysaccharide microsphere suspension (Sephadex), coronary flow of isolated perfused rat hearts was reduced by approximately 70%. During this Sephadex-induced ischemia, the energy charge and creatine phosphate content of the myocardial tissue dropped significantly, while total nucleoside and lactate release from the heart increased. During hypoxia (30% O2), changes in high-energy phosphate content and lactate and nucleoside release were similar to the changes induced by ischemia. During hypoxia, coronary flow rate was increased by 47%. Thus, Sephadex-induced reduction of coronary flow could be a useful model in studies of metabolic change during ischemia.


Turnover rates of muscle proteins in cardiac, skeletal, and smooth muscle: turnover rate related to muscle function.

The turnover rate of muscle proteins was related to the physiological function of the muscle in dogs, fowl, rats, and mice. The turnover rates of mixed muscle proteins were most rapid in cardiac muscle, intermediate in red tonic and mixed fiber-type muscles, and slowest in white twitch skeletal muscle. This same progression in  turnover rates also was shown in the subcellular fractions of muscle-sarcoplasmic and myofibrillar proteins-as well as in purified proteins, myosin, and tropomyosin. The RNA concentration of muscle was highly correlated with the protein turnover rate, and the RNA activity, i.e., the translational efficiency of the RNA, was similar in the different muscle types.


Elemental composition of ischemic myocardium determined by x-ray microanalysis.

Elemental composition of ischemic myocardium was attempted with x-ray microanalysis. Energy dispersive spectrum exhibited calcium K alpha and phosphorus K alpha peaks from mitochondrial deposits, and Ca K alpha peaks from nucleus, contraction bands, and Z lines of the ischemic myocardial cell. Ca and P contents were confirmed with wavelength dipersive spectrometers. Mg was present in the mitochondrial deposits which lacked Ca. This study suggests a formation of phosphate salt of Ca at different intracellular sites and also of Mg with mitochondrial deposits.


Ultrastructural features of diseased human atrial muscle cells.

Left atrial myocardial tissues, excised at the time of surgery from 30 Japanese patients, were studied using light and electron microscopy and the freeze-fracture technique. All had mitral valvular disease, and, in 22 (74%) patients, atrial fibrillation also was present. In all patients, most of the left atrial cardiocytes were hypertrophied and surrounded by various amounts of fibrous tissue. Degenerative alterations included large masses of lipofuscin granules and lamellar bodies, disorganized myofibrils, widened Z-line material, selective loss of thick filaments, and prominent tubules of sarcoplasmic reticulum. A high incidence of tubular aggregates was observed in 70% of the cases. Such alterations were seen more often in the mitral regurgitation group as compared to the mitral stenosis group. Atrial cardiocytes were found to be more susceptible to disease processes, such as rheumatic fever and subsequent pressure and/or volume overloading, than ventricular cardiocytes. Human atrial cardiocytes may be utilized in future cytopathological studies to study the effect of processes leading to cardiocyte hypertrophy and degeneration.


Is there a calcium-caused defect of oxidative phosphorylation in cardiomyopathic hamster hearts?

Mitochondria from cardiomyopathic hamster hearts have elevated calcium levels, which may cause a defect of oxidative phosphorylation in a small fraction of them. Using a combination of dual labeling density-gradient centrifugation, it was not possible to isolate such an abnormal fraction. However, cardiomyopathic mitochondria are more susceptible to damage by calcium in vitro, suggesting that an abnormal fraction does exist nevertheless.


Myocardial metabolism of spontaneously hypertensive rat.

Oxidative phosphorylation of myocardial mitochondria isolated from spontaneously hypertensive rats (SHR) was determined polarographically. The concentrations of high-energy phosphate compounds, the concentrations of intermediate metabolites, and the activities of the enzymes within the metabolic systems of glycolysis, the pentose phosphate (PPh) cycle, and the tricarboxylic acid (TCA) cycle of the myocardium of SHR were determined. The gradual development of cardiac hypertrophy was observed in SHR in comparison with normotensive Wistar rats. There were no significant differences in the function of oxidative phosphorylation of the mitochondria, in concentrations of high-energy phosphate compounds and carbohydrate metabolites, or in activities of glycolytic enzymes between SHR and normotensive Wistar rats.


Reduced response of cardiac norepinephrine release to isometric handgrip exercise in heart failure.

In order to evaluate the relation of cardiac norepinephrine (NE) release to left ventricular function, blood was taken simultaneously from the coronary sinus (CS) and the aorta (A) in 19 patients with heart diseases, at rest and during isometric handgrip exercise (IHG) at 30% of their maximal contraction. Plasma NE was analyzed by Renzini's THI method. The concentrations of plasma NE at rest were 397 +/- 66 (S.E.M.) ng/liter in CS and 292 +/- 50 in A. IHG significantly increased NE to 578 +/- 88 in CS and to 462 +/- 85 in A (p less than 0.001). Estimated NE release from the heart (deltaNE = NECS - NEA) correlated inversely to left ventricular end-diastolic pressure at rest (r = -0.520, p less than 0.05) and during IHG (r= -0.689, p less than 0.01). The changes in deltaNE induced by IHG correlated to the slope of the left ventricular function curve (r=0.618, p less than 0.01). It is concluded that the response of cardiac NE release to exercise is reduced in patients with depressed cardiac function.


The influence of plasma volume changes on enzymatic estimation of infarct size.

In 18 patients, myocardial injury was estimated by mathematical analysis of the rise in plasma activity of alpha-hydroxybutyrate (alpha-HBDH) dehydrogenase as observed by multiple sampling after admission. This enzyme represents the lactate dehydrogenase isoenzymes LDH1 and LDH2. Changes in plasma volume were assessed by determining hematocrit values at the same time as the enzyme activities. Infarct size was expressed in IU/liter of plasma and in grams of heart muscle per liter of plasma (g/liter). Significant changes in plasma volume, reflected in hematocrit changes, occurred (average 12%): 10 patients without pulmonary edema showed an average change of 7%; for the group of eight patients with pulmonary edema, the change was 17%. When calculated infarct size was not correlated for plasma volume changes, a significant overestimation occurred (11.7%, range 0.7-29.7%). In the subgroup of patients with pulmonary edema the mean overestimation was 15.8%, and in patients without pulmonary edema, the mean overestimation was 8.5%. It is concluded that plasma volume changes after an acute myocardial infarction have to be taken into account when infarct size is calculated on the basis of plasma enzyme levels.


Experimental study on enzyme distribution and its relation to myocardial ischemic changes following coronary circulatory disturbances.

Coronary artery ligation of canine heart was performed to investigate the relationship between the lactate dehydrogenase (LDH) pattern in myocardium and the distribution of coronary flow, especially in the early stage of ligation and after reperfusion. In the myocardium of normal dogs, the LDH pattern was similar in the left ventricle, the interventricular septum, and the right ventricle; the average LD5:LD4 ratio was 1.1, 1.2, and 1.2, respectively, and consisted mainly of heart type. In the left and right auricles, however, the ratios were 0.3 and 0.2, respectively, lacking heart type. In the left ventricle, LD5:LD4 ratio in the subendocardium was different from that in the subepicardial layer. Blood flow distribution in canine myocardium was investigated by the fluorescent pattern on the cut surface of heart, in which 10% fluorescein sodium was injected into the cavity. By this method the evolution of the ischemic area from the endocardial layer to the epicardial side following coronary artery ligation and the effect of reperfusion on the ischemic area were clarified. Electron microscopic studies indicated that loss of mitochondrial function may account for the irreversibility of myocardial cell alteration. A new method for studying enzyme localization in tissues was introduced for studying LDH isoenzyme distribution in normal and injured myocardium.


Nucleic DNA and RNA in cardiac muscle cell of experimental myocardial infarct.

Myocardial infarction was produced in dogs, and the changes in nucleic acid synthetic activity were investigated quantitatively by microspectrophotometer in the myocardial cells as time progressed. DNA value, immediately after infarction, was greatly increased in comparison to that of the control group. At two weeks after infarction the value had increased to the highest level. After this point the value decreased, and, in 12 weeks, the mean value was back to the control level. Changes in RNA followed a pattern similar to DNA changes. The mechanism of the repair process of myocardial infarction was investigated.


Dopamine-beta-hydroxylase activity after acute myocardial infarction.

After acute myocardial infarction, serial serum dopamine-beta-hydroxylase (DBH) activity was elevated in both high and low DBH subgroups. The observed increase in DBH activity on the first, second, and third days after acute myocardial infarction suggests an augmentation in sympathetic nervous system activity after acute myocardial infarction.


Release of lysosomal enzymes during ischemic injury of canine myocardium.

The pathobiology of the process of myocardial injury during ischemia comprises a series of events that results in the release of lysosomal enzymes from their subcellular locations within the myocardium. We have developed a canine model of acute myocardial ischemia in which the anterior descending coronary artery is ligated, myocardial blood flow is measured using radioactive microspheres, and tissues from subendocardium and subepicardium are assayed for activity of lysosomal hydrolases:N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta-gluc), and acid phosphatase (AP). Particulate fractions of subendocardium revealed significant depletion of of total acid hydrolases (NAG, beta-gluc, and AP) after one and two hours of ischemia. In addition, after two hours of ischemia, the total activity of these three hydrolases in the subendocardial supernatant was decreased, correlating significantly with diminished myocardial blood flow (NAG: r =0.96; beta-gluc: r = 0.95; AP: r = 0.75). The diminished enzymatic levels in thesupernatant suggested "washout" of the hydrolases that was more efficient in those ischemic areas that had higher myocardial flow (greater than 20% of control). These changes in distribution of lysosomal hydrolases indicate early involvement of these enzymes in the pathobiology of myocardial injury and demonstrate the dynamic relationship of "washout" of acid hydrolases with the degree of diminished blood flow.


Pepstatin inhibition of rat myocardial acid protease.

The protease inhibitor, pepstatin, inhibited acid protease in rat heart homogenates with a Ki of 7 x 10(-11) M by a noncompetitive mechanism, but it had no effect on myocardial acid protease activity when given in high doses to intact animals. Exposure of heart slices to 10(-7) M pepstatin for two hours also failed to produce demonstrable acid protease inhibition, suggesting that myocardial acid protease activity is unaffected by this potent inhibitor unless the integrity of the cell is disturbed.


Features of lysosomal proteolytic enzyme activity in infarcted myocardium.

Myocardial infarction was produced in dogs to investigate the behavior of cardiac lysosomal enzymes; acid protease and beta-glucuronidase activities were measured in whole myocardial homogenate and 30,000 X g supernatant fractions. Total activity of acid protease in the whole homogenate of the myocardium increased after 1 hr of infarction and showed maximal value after 6 hr, while in the 30,000 X g supernatant fraction the activity began to increase after 3 hr and reached the maximal level by 24 hr. Total beta-glucuronidase activity in the whole homogenate decreased during the initial 3 hr after myocardial infarction and markedly increased after 12 hr. The activity in the 30,000 X g supernatant fraction showed corresponding changes. These findings that the increase in whole homogenate activity preceded that in the 30,000 X g supernatant fraction may support the hypothesis that lysosomal enzymes may be newly synthesized and then solubilized in the infarcted myocardium.


Autophagy in cardiac myocytes.

The fetal mouse heart (FMH) in organ culture continues to beat for a period of weeks, but degenerative changes occur. Electron microscopy revealed formation of autophagic vacuoles containing damaged organelles in some cells after the first day, indicating focal cytoplasmic injury. This process was accelerated by transient deprivation of oxygen and glucose followed by resupply of oxygen and glucose. FMHs were maintained for up to four hours in glucose-free media in an atmosphere of 95% N/5% CO2 followed by resupply of O2 and glucose. Twenty-four hours later, many cells recovered without residual injury. Many others revealed autophagic vacuoles ranging from those in which organelles were readily identified to those characteristic of residual bodies. It appears that focal injury stimulates the endoplasmic reticulum to enclose the damaged components, permitting localized lysosomal digestion without causing injury to the entire cell. Autophagy has not been emphasized as an important mechanism in transient ischemia in adult myocytes, but it may play a role in repair of sublethal injury. The FMH organ culture provides an excellent model for studying the sequential autophagic changes in a system in which these events can be accelerated.


Changes in purine nucleoside content in human myocardial efflux during pacing-induced ischemia.

Pacing-induced myocardial ischemia in 18 patients resulted in an increase of coronary sinus hypoxanthine levels from 1.20 +/- 0.18 micron during control to 2.41 +/- 0.52 micron (p less than 0.025) during pain. In addition, early lactate production occurred frequently before angina was noted. Neither hypoxanthine nor lactate levels changed in seven nonanginal patients, nor were significant alterations in potassium, inorganic phosphate, glucose, or oxygen saturation found in all patients. Myocardial hypoxanthine production seems a useful indicator of ischemia in the human heart.


Myocardial protection during open-heart surgery: preservation of myocardial metabolism and ultrastructure by cold coronary perfusion.

Myocardial protection by means of selective, continuous coronary perfusion with cold oxygenated blood of low flow rate and of low perfusion pressure is an excellent procedure both clinically and experimentally. This method should be particularly useful in poor-risk patients, for whom a maximal preservation of the myocardium is imperative.


Preservation of myocardial membrane integrity in the early phase of acute myocardial ischemia.

Myocardial uptake of dexamethasone (Dex) or methylprednisolone (MP) was studied using tritiated tracers in isolated perfused cat hearts during acute myocardial ischemia. Considerable amounts of Dex and MP were incorported into the plasma membranes in control, border-zone, and ischemic myocardium. Lesser amounts were bound to the remaining subcellular organelles. A gradient of the glucocorticoid uptake was observed decreasing from control myocardium to ischemic myocardium in all subcellular fractions. By the first hour of ischemia, the myocardial plasma membranes underwent marked depletion of activity of 5'-nucleotidase, a plasma membrane marker enzyme, indicating early loss of plasma membrane integrity in acute myocardial ischemia. The incorporation of Dex or MP into the plasma membranes resulted in a significant decrease in loww of 5'-nucleotidase activity of the plasma membranes in the border-zone and ischemic myocardium. The data provide direct evidence 1) to support a membrane stabilizing action of glucocorticoids, and 2) to focus on the plasma membranes as a potentially important site of protection during the early phase of acute myocardial ischemia.


Effect of physical fitness on myocardial damage and circulation after myocardial necrosis.

The effect of physical training (conditioning) on myocardial circulation and myocardial damage has been evaluated in experimental myocardial necrosis in albino rats. Conditioning was done by making the animals swim in a tank of water, thermostatically controlled at 32 degrees +/- 1 degrees C, 60 minutes daily, six days a week, for eight weeks. Myocardial necrosis was produced by subcutaneous injection of isoproterenol, 85 mg/kg body weight, on two consecutive days. Investigations included ECG (lead II), SGOT, SGPT, SLDH, SCPK, histopathology of the heart, and myocardial Rubidium 84 uptake. It was observed that, in conditioned animals, elevation of serum enzymes was less, incidence of cardiac arrhythmia was lower, myocardial damage was less marked, and myocardial circulation was better after myocardial necrosis in comparison to unconditioned animals. Less myocardial damage and lower incidence of cardiac of cardiac arrhythmia are presumably associated with a better prognosis.


Pharmacological protection of hypoxic heart.

The ability of beta-adrenoceptor antagonists, with and without intrinsic sympathomimetic activity, and of verapamil to protect the heart against hypoxia-induced damage was investigated. Damage was quantitated in terms of a raised end-diastolic resting tension and creatine phosphokinase (CPK) release. The results indicate that both the d and the l isomers act differently, the isomers preventing CPK release and the d isomers preventing the increase in resting tension.


Experimental studies on myocardial metabolism of carbohydrates and lipids in surface-induced deep hypothermia.

In surface-induced deep hypothermia, metabolic acidosis resulting from lactacidemia was observed. In the hypothermic heart, the rate of reduction in the coronary arteriovenous (A-V) difference ratio of lactate, pyruvate, and nonesterified fatty acids (NEFA) was proportionately less than that of coronary flow and myocardial oxygen consumption, suggesting that lactate, pyruvate, and NEFA play important roles as energy fuels in the hypothermic heart. Myocardial metabolism of glucose was reduced; exogenous corticosteroids and ATP do not influence the myocardial metabolism of carbohydrates and lipids in the hypothermic heart.


Studies on experimental coronary insufficiency. I. Effects of a physiological dose of adrenaline and noradrenaline on myocardial metabolism in dogs with graded coronary constriction.

To investigate the mechanism by which catecholamines produce myocardial ischemia, the effect of intracoronary-administered adrenaline and noradrenaline was studied in dogs with graded coronary constriction. A physiological dose of catecholamines was favorable for augmentation or improvement of myocardial metabolism and cardiac function in dogs without or with slight coronary constriction. However, in dogs with moderate or severe coronary constriction, similar doses of catecholamines produced myocardial ischemia and cardiac dysfunction.


The effects of coronary artery ligation on transmural high-energy phosphates following 20 minutes of blood reflow.

Normal or elevated levels of ATP and phosphocreatine (PCr) were observed from the subepicardium to the subendocardium of the canine left ventricle after five and 20 minutes of left circumflex artery occlusion followed by 20 minutes of blood reflow. However, after two or four hours of occlusion, followed by reflow, ATP and PCr levels were markedly depressed, and a significant decreasing decreasing subepicardial to subendocardial gradient appeared, suggestive of inhibition of oxidative metabolism during extended periods of ischemia but not during short periods of ischemia.


Studies on experimental coronary insufficiency. II. Effects of beta-adrenergic blocking agent (propranolol) on metabolic response to adrenaline and noradrenaline in dogs with coronary constriction.

To obtain further information on the mechanism by which catecholamines produce myocardial ischemia, the effects of propranolol on metabolic and mechanical responses to adrenaline or noradrenaline were investigated in coronary-constricted dogs. Propranolol suppressed the myocardial ischemia produced by noradrenaline and adrenaline in dogs with moderate coronary constriction.


Transmural gradients in ischemic canine left ventricle: effects of blood reflow on glycolytic intermediates.

Following two and four hours of left ventricular ischemia, 20 minutes of blood reflow cannot produce a complete return to normal oxidative metabolism in ischemic canine myocardium. Glycolysis remains increased and aerobic metabolism is most extensively depressed in the subendocardium.


Ultrastructural change in myocardium subsequent to ischemic cardioplegia "no-reflow phenomenon".

Mongrel dogs were subjected to cardiopulmonary bypass with hemodilution and to normothermic anoxic arrest for 30 minutes, to study the subepicardial and the subendocardial myocardial ultructure and the DPTI/TTI ratio. "No-reflow phenomenon" was demonstrated in the myocardium after cardiopulmonary bypass, associated with normothermic anoxic arrest. No-reflow phenomenon was a contributing factor to subendocardial ischemia in the normotrophied ventricle after open-heart surgery. Severe hemodilution with hemoglobin less than 5.0 g% resulted in irreversible damage in both myocardial layers.


Coronary microcirculatory factors and cardiac muscle cell injury.

Coronary artery ligation with or without reperfusion was carried out in Wistar rats to study the role of coronary microcirculatory factors and membrane permeability alteration of cardiac muscle cell in the evolution of cardiac muscle cell injury by using the fine structural extracellular protein tracer, horseradish peroxidase (HRP). The findings were compared with those obtained in noncoronarogenic myocardial injury models following administration of norepinephrine, a pressor, and isoproterenol, a depressor catecholamine. Following left coronary artery ligation lastingfor 10 and 20 minutes, some of the collaterals in the ischemic zone were perused by the tracer, but the numer of patent capillaries decreased during 60-min ligation. The inhomogeneous involvement of cardiac muscle cells in ischemic injury correlated well with these microcirculatory findings. In comparison to permanent ischemia, an abrupt deterioration of the cardiac muscle cell alteration occured after reperfusion with influx of HRP into the damaged cells. The binding of tracer to myofilaments was, however, a later event as compared to that seen in the catecholamine models. The latter observation implies that, in addition to microcirculatory factors, direct cardiac muscle cell stimulation should also be considered in the evolution of noncoronarogenic myocardial injury.


Viability and histopathology of eleven fresh, antibiotic-treated allografts removed three weeks to three years after implantation.

Changes in metabolic activity of removed heart valve allografts have been measured. The fresh heart valves were sterilized and stored in antibiotic solution before implantation in patients. Viability was determined before insertion and after removal from patients by two methods: 1) tissue culture, and 2) autoradiography, using tritiated thymidine. The length of storage in the Hank's antibiotic or nutrient-antibiotic medium before insertion did not seem to influence the final metabolic activity nor the structural integrity of the allografts when they were removed. Results from the present study show that the most severe degenerative changes occur in valves stored in Hank's solution and then implanted in the mitral position. The viability percentage declined progressively during the time that a valve treated in this manner was functioning in a patient.


Evaluation of perfusion conditions in cardiopulmonary bypass.

Fresh sections of left ventricular drill biopsies, taken at the beginning and end of cardiopulmonary bypass in 164 patients undergoing aortic valve replacement, have been analyzed for myocardial function. This has been assessed by changes in biochemical function, measured by semi-quantitative histochemical methods, and by changes in birefringence, measured quantitatively by polarization microscopy. It has been shown that continuous perfusion at 32 degrees C with the heart beating provided better preservation than did the other three perfusion procedures, in all of which the heart was fibrillating. More recently, in a small number of cases, cardioplegic arrest has been found to given even better preservation.


Effect of environmental factors and tissue culture methodology in producing and studying cultured cardiac cells.

Improvement in the method of heart cell cultures is described and justified in relation to environmental factors. The validity of such cardiac cell culture for cardiac research is discussed in light of particular cellular activities: differentiation of lipoprotein lipase, myoglobin biosynthesis, glucose and fatty acid metabolism pleiotypic responses (rotein, RNA, and DNA biosyntheses, substrates transports) to serum stimulation, and the architectonic growth of muscle and nonmuscle cells.


Palmitate oxidation by beating heart cells in culture.

Palmitic acid oxidation has been studied in cultures of beating heart cells. The data reported suggest: 1. The main source of fatty acids for oxidation in cell cultures is provided by lypolysis of preexisting intracellular fatty acids. Most fatty acids that have just entered the cell are not oxidized immediately. Thus, aged heart cells in culture seem to retain their ability to utilize fatty acids as their main energy source. 2. In cultured heart cells, the amount of CO2 obtained from the carboxyl group was much higher than that obtained from the methyl group. On the other hand, beta-hydroxybutrate has been shown to be formed mainly from the methyl group. This may indicate that beta-oxidation terminates at the beta-hydroxybutyrate stage because of premature dissociation of this last intermediate from the enzyme complex.


Pleiotropic effect of serum on beating rat heart cell cultures and their modulation by hormones.

The multiple effects of serum on metabolic activities and macromolecular syntheses of heart cell cultures are discussed in this chapter. This pleiotropic response, which is linearly related to the amount of serum used, allowed us to quantitatively test the growth-promoting activity of different hormones. In addition, the possible mediation of the serum effects by cyclic nucleotides is considered.


Ouabain-induced arrhythmias of cultured myocardial cells and their improvement by quinidine.

Single-isolated myocardial cells obtained in vitro from fetal mouse heart developed various types of arrhythmic movements, such as fibrillatory and fluttering movements, in medium containing ouabain. The percentage of isolated myocardial cells that exhibited arrhythmic movements increased as ouabain concentration was increased. The arrhythmic movements induced by relatively low concentrations of ouabain were reduced by addition of quinidine. Cell clusters also developed various types of arrhythmic movements in medium containing ouabain. These arrhythmias became more severe when the ouabain concentration was increased. Under conditions such that approximately 43% of the single-isolated myocardial cells showed arrhythmias, many cells in cell clusters showed fibrillatory movements, but the cell clusters as a whole still maintained rhythmic beating. Under conditions in which about 65% of the single-isolated myocardial cells showed arrhythmias, cell clusters as a whole showed irregular beating. The cell clusters stopped beating under conditions in which about 79% of the single-isolated myocardial cells showed arrhythmias. Relatively mild types of arrhythmias of cell clusters were improved by addition of quinidine. From these observations, the genesis and improvement of arrhythmias of cell clusters were concluded to be essentially a result of the genesis and improvement of arrhythmic movements of the individual component cells in the clusters.


Experimental studies on cardiac arrhythmias with special reference to fibrillation in heart cell culture.

Fibrillation-like beating of cardiac muscle cells in culture was induced by altering the concentrations of various ions. Fine structural changes of cell membrane and intercellular alteration of cardiac muscle cells appeared to be more prominent in cells with fibrilliation-like beating than in others. From the results of the present study, it may be concluded that fibrillation-like beating may occur in the presence of altered concentrations of certain ions, accompanied by fine structural changes in the cells.


Fucosidosis: diagnosis of five patients and carrier detection.

The clinical and biochemical data of the two original cases of fucosidosis type I and of three other type II are reported. Of less than forty patients affected with fucosidosis, described in the literature, seven belong to two pedigree originating from a small, isolated area of the Southern Italian region of Calabria. All the affected children were born from first cousin marriages. Clinical heterogeneity has been observed inside both pedigrees and some patients show angiokeratoma while others do not.


Fucosidosis: a neuropathological study.

The involvement of the central nervous system in fucosidosis is related to severe lesions of both nerve and glial cells. The morphology of cells degeneration is characterized by both vacuoli containing water-soluble fuco-derivatives (fuco-oligosaccharides) and/or granular substances probably constituted by fuco-sphingolipds. The cerebral cortex is the most severely affected. The involvement of the white matter is related to the glial cells degeneration. The relationship between the morphology of nerve and glial cells lesions, and the accumulation of oligosaccharides and sphingolipids following the absence of alpha-L-fucosidase, is briefly discussed.


Synthesis and phosphorylation of canine cardiac myosin in tissue-culture assessment of hypertrophying factors.

Canine cardiac myosin, which was synthesized in a 14-day tissue culture, based on L-[3H] leucine incorporation, was precipitated with goat gamma G antimyosin (cardiac-specific) and analyzed on dodecylsulfate gels. Incorporation of 32PO4 into myosin chains occurring in culture was the same as that obtained in vivo and appeared to be coupled with translation. Removal of 32PO4 from myosin heavy chains with base treatment indicated the presence of phosphoserine and phosphothreonine in canine cardiac myosin heavy chains. Further acid hydrolysis confirmed the data. The system described here, i.e., analyses of 32PO4 and L[3H] leucine incorporation into myosin heavy chains, could be used as a system for assaying hypertrophying factors.


[Familial myotonic syndrome with hyposthenia corrected with exercise (author's transl)].

In some cases of myotonic syndromes a paresis after rest has been described corrected by exercise. This syndrome is reported in two brothers. In myotonic patients repetitive stimulation of a nerve causes a transitory decrease of the muscle action potential. Probably the paresis corrected by exercise only represents the clinical evidence of the electrophysiological phenomenon mentioned above. This seems to be a common occurrence and therefore does not represent a new nosologic entity.


The syndrome of carnitine deficiency.

Three cases of lipid storage myopathy and carnitine deficiency are presented. Two had a fatal course and were insensitive to cortisone and carnitine-replacement therapy. The two fatal cases had lipid accumulation in organs other than the skeletal muscles and carnitine was reduced in plasma, skeletal muscles, heart and liver. Fibroblasts from one of these "generalized" cases of carnitine deficiency were grown from a skin biopsy. Carnitine level, fatty acids uptake and oxidation were not appreciably different between the patients' fibroblasts and those of controls.


The neurophysiological features of various diseases with NCL storage.

Combined EEG/ERG/VER studies were carried out on 47 children with verified neuronal storage of ceroid/lipofuscin-like material. The majority of patients fell into one of three main groups. Each group showed its own characteristic combination of neurophysiological features which were of diagnostic importance and closely parallel to the age of onset and the evolution of clinical symptoms characteristic to each group. These findings suggest that general terms such as "NCL" or "Batten's disease" imply a single disease process and are misleading.


Fine structure of the conduction system and working myocardium in the little brown bat, Myotis lucifugus.

In the little brown bat, Myotis lucifugus, topography and ultrastructure of the sinus node and the atrioventricular (AV) node resemble those in large mammalian hearts, except that the P cells in the sinus node are smaller than those in the bat AV node or those in the sinus node of slower hearts (e.g., dog, man). Despite rich innervation in the bat nodes, true neuromuscular synapses are rarely formed. Bat working cardiocytes have a well developed sarcoplasmic reticulum, but otherwise resemble working myocytes of larger mammals.


Recent findings on some "new" neurometabolic diseases.

The most common inborn error of glycoprotein catabolism appears to be aspartylglycosaminuria (AGU). It is characterized by deepening mental retardation, progressive lesions of connective tissue, and increased urinary excretion of aspartyglycosylamine. The first symptoms usually appear after 3 years of age and closely resemble those of Hurler's disease. The condition is a hereditary lysosomal storage disease due to a defective enzyme. The main clinical findings in a infantile type of neuronal ceroid-lipofuscinosis (INCL) are psychomotor retardation, visual failure, and a virtually isoelectric E.E.G. at the final stage of the disease. The symptoms of this hereditary disorder first appear between 8 and 18 months of age and the mean age at death is 6.5 years. Striking cerebral and cerebellar atrophy, together with neuronal loss and accumulation of lipofuscin-like material, can be observed at neuropathological examination.


Studies on the clustering of multiple sclerosis in Finland.

The epidemiological investigation of multiple sclerosis (MS) in Finland revealed a prevalence rate of 40.3 per 100.000 inhabitants. The geographic distribution of MS was uneven in the country. MS seemed to occur more often in the western and southwestern parts of the country, where the prevalences varied between 51.7 and 62.1 This phenomenon became even more pronounced when the distribution of the disease was investigated in small geographic units. Optic neuritis showed a geographic distribution similar to that of MS, with clustering in the same parts of the country and even in the same narrow districts. The correlation between the birthplaces of MS and optic neuritis patients was very significant (p less than 0.001), which suggest that they share a common aetiology. The possible aetiological role of genetic and exogenous factors was discussed in the western cluster of MS, where the percentage of familial cases was 13 and an accumulation of muscular dystrophy of cattle was observed.


Epidemiological survey on multiple sclerosis in Italy.

An epidemiological survey on Multiple Sclerosis was carried out in 1975 with similar methods in 9 italian provinces: 4 in the North, 2 in central Italy and 3 in the south and islands. It was found that the incidence of the disease was partically uniform in the northern provinces, in the central Italy and in Bari province. It is important however to complete in greater detail such survey in the south of Italy where the data are still incomplete.


Myocardial depressant factor and rat heart myoblasts in tissue culture.

Beating rat heart myoblasts in tissue culture are suitable for the demonstration of the effect of sera from patients with cardiogenic shock upon the contractility of heart muscle. Shock serum either promptly stops beating or causes discoordinated movements of the cultivated myoblasts (fibrillation). This effect of the shock serum is concentration-dependent. Hydrocortisone before and/or after treatment of the cultivated cells does not influence the effect of the shock serum. Calcium ions shorten the period of standstill of the muscle cells after washout of the shock serum.


[A case of visual agnosia for objects (author's transl)].

Following an ischemic accident in the territory of the left posterior cerebral artery, a 71 year-old woman had a severe disorder of visual recognition of objects while she quickly identified them by touch. Visual recognition of pictures, written symbols, colours and, to a lesser degree, faces was also impaired. A careful examination showed that the patient's defect could not be accounted for by general intellectual impairment, language disorder, visual acuity, or pattern discrimination deficit. These findings are consistent with the classical concept of associative agnosia: the pathophysiology of the syndrome is discussed.


Cardiotoxic effects of adriamycin in mammalian cardiac cells in culture.

Cardiotoxicity of unknown etiology may preclude the use of adriamycin, a cancer chemotherapeutic agent. Mammalian cardiac cells in culture were used as a model system in the study of the mechanisms involved. Adriamycin inhibited cell growth, particularly of the fast-dividing nonmuscle cells. This inhibition might be a contributory factor to cardiomyopathy, but it does not explain the cessation of the rhythmic contractions characteristic of myocardial cells in culture. The concentrations of ATP and phosphorylcreatine (PC) were decreased in the adriamycin-treated cells, but the addition of creatine resulted in a several-fold increase of PC. Therefore, the regulation of energy production and the potential to maintain a high, steady-state concentration of PC were not impaired.


[The Rorschach test during chronic haemodialysis (author's transl)].

Twenty-eight patients undergoing chronic haemodialysis for renal failure and seven patients suffering from chronic uremia, but not on dialysis programs were submitted to the Rorschach test. The patients who were undergoing haemodialysis for less than one year showed higher signs of anxiety (shock and Hd responses); on the other hand patients undergoing the treatment for more than 5 years showed a generally worse quality response to the test. This bad performance was interpreted either as a sign of organic brain damage or as a worse cooperation in the test procedure.


[Space requiring intracranial conditions and pregnancy].

Gravidity and the intracranial process are discussed in view of the question of whether to carry out an interruption of pregnancy or to carry the pregnancy to full term and end it by means of Cesarean section, on the basis of literature and 5 observations.--It is recommended to work out an individual plan of treatment together with the obstetrician and the neurologist. It was shown that there is a possibility of an operative treatment of intracranial processes of different genesis even in the advanced stage of pregnancy and with the continuation pregnancy.


[Qualitative function test of ventriculo-atrial drainage using Cordis-Hakim valves].

Description of the acoustic detection of the functional performance of Cordis-Hakim valves. This can be monitored or perceived with a surface microphone, or demonstrated by means of an oscilloscope. To document the findings the image of the viewing screen can be photographed or continuously registered through interconnection of a recorder. There is also the possibility of testing with the stethoscope. The construction of the device and experimental arrangements are described.


[Reperfusion following cerebrovascular arrest].

An account is given of a case of artificial perfusion of isolated organ after operative correction of an angiographically recorded standstill of the circulatory system. Criteria of cerebral death and determination of the time of death are discussed.