Three cases of sinoatrial block induced by anticonvulsants. Diphenylhydantoin (DPH) and Carbamazepine have been widely used as anticonvulsants and known to have antiarrhythmic properties. Previous reports have shown that arrhythmias such as sinus bradycardia and atrioventricular block can be induced by these agents. In this paper, sinoatrial block (SA block) induced by these agents which were used as anticonvulsants in 3 aged patients is reported. Thre patients, 2 women and 1 man, were over 60 years old. In 2 cases, administration of DPH for recurrent epileptic seizures was followed by SA block. After withdrawal of DPH, SA block disappeared, but resumption of DPH resulted in SA block again. In 1 of these 2 patients, overdrive suppression test revealed normal sinus node recovery time. In the third patient, in addition to DPH which was administered for epileptic seizures, Carbamazepine was given for shoulder pain, then SA block occurred. Withdrawal of these agents restored normal sinus rhythm and combined administration of these 2 agents again induced SA block. Autopsy revealed decreased conduction cells in the sinus node.


Glucose metabolism in spontaneously hypertensive rats. Serum glucose levels in SHR (especially SHR selected for a greater hyperglycemic response) tended to be higher at 'fasting' and were significantly higher after peroral glucose administration than those in normotensive WK. However, plasma immunoreactive insulin was not decreased in SHR as compared with WK. No significant acceleration of gluconeogenesis was observed in SHR.


Enzymatic histo and cytochemical investigation on the cardiovascular system in spontaneously hypertensive rats. The functional abnormalities of the cells in the cardiovascular system in SHR were revealed by enzyme histo-cytochemical study. The enzymatic activity was usually increased in the area where the arteries branched and in proliferating cells in the thickened wall. Such was more remarkable in the distorted arteries with aging. Functional roles of these 4 enzymes were discussed.


Biomembrane characteristics in stroke-prone spontaneously hypertensive rats (SHRSP). Biomembrane characteristics in stroke-prone SHR (SHRSP) and stroke-resistant SHR (SHRSR) were examined using erythrocytes as a simplified model. When erythrocytes were exposed to osmotic stress in the process of the migration from a higher to a lower osmotic gradient by the coil planet centrifugation, erythrocytes from SHRSP were hemolyzed at a higher osmotic pressure than those from SHRSR. Such a difference in biomembrane characteristics may be useful for detecting a genetic disposition of stroke.


Genetic subgrouping of stroke-prone SHR and stroke-resistant SHR. From these results, we can conclude that the developmental pattern of hypertension in the young age is genetically determined and closely related to the incidence of hemorrhage or infarction. These newly selected substrains of SHRSP with higher incidences of cerebral infarction (SP-2) or hemorrhage (SP-1) are regarded as the better models for studying the pathogenesis, treatment, and prevention of infarction or hemorrhage, respectively.


Effect of acute arterial hypertension in stroke-prone and stroke-resistant SHR. Acute transient hypertension by norepinephrine was loaded to stroke-resistant (SHRSR), stroke-prone (SHRSP), and normotensive Wistar Kyoto (WK) rats. (SHRSP were most sensitive to norepinephrine in young pre-hypertensive group.) Its effects on cerebral small vessels were studied using Evans Blue to detect the increase of vascular permeability. Severe macroscopic dye-leakages were observed in the areas of "recurrent branching" and "boundary zone", especially among young SHRSP, while SHRSR seemed to be least prone to dye-leakage both in young and adult groups. Among the adults, there was little difference between SHRSP and WK, probably because of the adaptive structural changes of arterial walls in SHRSP caused by long-standing hypertension.


Cerebral stroke and myocardial lesions in stroke-prone SHR. 1) The histopathological abnormalities of the heart tended to be slightly severer in SHRSP with cerebrovascular lesions than those without cerebrovascular lesions. 2) However, SHRSP without cerebrovascular lesions also indicated abnormalities of VCG and histopathological findings. 3) Therefore, cerebral stroke may not directly affect or engender such myocardial lesions. 4) It is still remained to be solved whether the dysfunction of the heart with organic changes may partially contribute to the occurrence of cerebral stroke. 5) VCG appeared to correspond to the organic changes of the heart.


Blood pressure in stroke-prone SHR (SHRSP) exposed to unusual environmental temperature. 1) It is generally accepted that the adequate environmental temperature to rear rats is about 23 degrees C, but the adequate temperature that directly contacts to the animal's skin seems to be about 30 degrees C. 2) The blood pressure increased on cold exposure or stimulation. There was a case that the blood pressure increased slightly on hot exposure. This suggests that it is necessary to pay close attention to the condition of warming-up at the indirect measurement of blood pressure. 3) Apoplexy seemed to occur earlier at the low environmental temperature, and the blood pressure seemed to increase also at the high temperature. However, these temperature effects on blood pressure and the incidence of stroke were not so obvious as observed in rearing SP with 0.9% salt solution for drinking.


Effects of chlorella alkali extract on blood pressure in SHR. When chlorella was treated with alkali after decolorization by methyl alcohol and then fractionated by gel filtration, the fraction showed a depressive effect. The blood pressure of SHRSP and SHR showed a fall of an average of 63 mmHG 1 hour after intravenous administration, 47 MMHg 2 hours after intraperitoneal administration. The blood pressure of normotensive Wistar rats also showed a fall of an average of 32 mmHg 1 hour after intravenous administration.


On the findings of stroke-prone SHR.

On the findings of stroke-prone SHR. The fundus of 82 SHRSP were observed and all of them showed the narrowing caliber irregularity of retinal arterioles and optic disc edema. Moreover, tortuosity of retinal arterioles was characteristic.


Fluorescein fundus angiography of stroke-prone SHR. The fluorescein fundus angiography was performed on SHRSP, SHR, and NR. The following results were obtained. 1. No expravasation of fluorescein from retinal vessels of SHR and NR was observed at any phase of circulation. 2. The extravasation of fluorescein from retinal arterioles and peripapillary capillary of SHRSP of post-hypertensive stage was seen at arterial phase of circulation. These extravasation of fluorescein coincided with the initial stage of stroke incidence.


The molecular weight and character of plasma renin in SHRSP. 1. The molecular weight was 49,800 in SHRSP, quite different from the 43,300 of WK and the 49,500 and 37,700 of SHR, in females at the age of 200 days. 2. The molecular weight of plasma renin of female WK at the age of 90, 120, and 200 days ranged from 41,000 to 43,000 showing little variation. 3. The molecular weight of plasma renin varied according to the elevation of blood pressure. When blood pressure were 163, 200 to 250, and 267 mmHg, it showed 40,500, about 50,000, and about 60,000, respectively. 4. When subjected to an acid treatment, the high molecular type of SHRSP, showing molecular weights of plasma renin of about 50,000 to 60,000, increased in plasma renin activity by from 1.3 to 4.0 times.


Cholesterol metabolism in spontaneously hypertensive rats. The absorption of radioactive cholesterol tended to be increased, and the catabolism of cholesterol detected by the decay of radioactive cholesterol in the serum after the intraperitoneal injection was delayed in ALR in comparison with normotensive WK rats. The reactive hypercholesterolemia in the ALR which had been selectively bred for a greater hypercholesterolemia was ascribed to the decreased cholesterol catabolism.


Sinoatrial response to premature atrial stimulation during atrial pacing in aged patients with and without sinus node dysfunction. Sinus node function was analysed in 15 aged patients, including 8 with sick sinus syndrome and 7 without apparent sinus node dysfunction, by rapid artial pacing and premature atrial stimulation during sinus rhythm and 5 beats of atrial pacing. Three patterns of sinoatrial response were identified by premature atrial stimulation during atrial pacing. Type I response (3 cases) represented approximately constant return cycles and type II (2 cases) represented a markedly prolonged return cycles following premature stimulation. Type III response was characterized by a progressive shortening of return cycles as the prematurity of atrial extrastimuli was increased. Underlying mechanisms responsible for these responses were discussed in relation to the sinus node automaticity and sinoatrial conduction.


Precordial ST-segment changes and serum enzyme levels in acute myocardial infarction. Serial study of 72-lead precordial ST-maps, SGOT, and SLDH was done in 30 cases of acute myocardial infarction. Infarct size was estimated by sum of ST elevation in all leads (sigma ST), number of sites showing ST elevation (NST), peak SGOT, and peak SLDH levels, and correlated with each other and with clinical features and hospital course. sigma ST correlated well with NST (r=0.92), but the correlations of sigma ST with SGOT (r=0.99) and SLDH (r=3.84) were better than those of NST with SGOT (r=0.22) and SLDH (r=0.53). There were close agreements between sigma ST and peak SGOT and peak SLDH except in the cases of non-transmural infarction, in whom smaller sigma ST suggesting small infract occurred with higher enzyme peaks indicating moderate or large infarct. Longer duration of chest pain, larger number of associated conditions (e.g. angina, hypertension, diabetes), complications (e.g. congestive heart failure, shock, arrhythmias) and mortality were associated with larger infarcts.


Echocardiographic evaluation of left ventricular filling in mitral stenosis. Role of atrial contraction. Echocardiographic evaluation of left ventricular volume change during rapid and atrial filling periods was made in patients with mital stenosis. The significant reduction of rapid filling volume was observed and the rate of rapid filling was approximately the half of normal in mitral stenosis. The rapid filling period showed a good correlation to the mitral valve area measured at operation. After surgical treatment, the rate of rapid filling was significantly increased but was still significantly smaller than normal. It was suggested that the remained structural abnormality of mitral apparatus depressed the inflow through the mitral valve in early diastole despite successful mitral valvotomy. Left ventricular filling during atrial contraction (atrial filling) was augmented twice as much as normal in patients with milder mitral stenosis, compensating the decreased early diastolic filling. In contrast, the atrial filling did not increase in severe mitral stenosis, resulting in the decreased cardiac output. Following mitral commissurotomy, the atrial filling in milder mitral stenosis was reduced but remained significantly larger than normal. There was no change of atrial filling in severe mitral stenosis postoperatively. This fact suggested the existence of impaired contraction of left atrium in cases with severe mitral stenosis. Our results show that the altered left atrial transport function plays an important role in the left ventricular filling in mitral stenosis.


Effect of amyl nitrite inhalation on the abnormal T loop of vectorcardiogram. The effect of amyl nitrite (AN) on the vectorcardiographic T loop was studied in 17 cases who had negative T waves in the left chest leads of ECG. Thirty sec after AN inhalation the maximum T vector was displaced to the left and anteriorly in 15 and to the left and posteriorly in 2 cases. The magnitude of maximum spatial T vector was decreased and the spatial T loop became more circular. Changes in the amplitude of T loop projected to the scalar lead X were closely related with changes in the heart rate which would represent the sympathetic tone.


Correlation between systolic time intervals and roentgen findings in normal subjects and cardiopathic patients. This study was designed to evaluate the usefulness of non-invasive parameters in the follow-up of cardiopathic patients without valvular cardiac diseases. In 49 patients suffering from heart disease we have studied the changes of radiologic cardiac measurements and systolic time intervals (STI) in the 4 functional classes of the NYHA classification, investigating also the existence of any relationship between these different parameters. Only the patients in the 3rd and the 4th functional classes showed significant changes in STI and radiologic measurements, as compared with the control group. Moreover, significant negative correlations have been observed between relative heart volume and LVET (r = 0.69, P less than 0.001) and LVETc (r = 0.82, P less than 0.001) and positive correlations between relative heart volume and PEP (r = 0.59, P less than 0.01) and PEP/LVET ratio (r = 0.75, P less than 0.001). These results, while confirming the close correlation between STI and cardiac performance, seem to demonstrate that relative heart volumetry is a fairly accurate index of the cardiac conditions in non-valvular heart diseases.


Role of renin-angiotensin system in the controls of blood pressure and aldosterone in patients with cirrhosis and ascites. In an attempt to evaluate the role of renin-angiotensin system in the contols of blood pressure and aldosterone secretion in the patients with cirrhosis and asictes, 7 patients were infused of an antagonist of angiotensin II, Sar-1 Ile-8 angiotensin II, intravenously to inhibit the action of renin-angiotensin system and to observe changes in arterial pressure and plasma aldosterone. In 1 patient with recent onset of severe ascites and high plasma renin activity, blood pressure and plasma aldosterone decreased during the infusion. In contrast, mild rise in blood pressure and various changes in plasma aldosterone were observed in the other 6 patients with normal plasma renin activity. These results suggest variable angiotensin dependency in the controls of blood pressure and plasma aldosterone in the patients with cirrhosis and ascites according to the stage of the disease, the states of sodium and water balance and/or palasma renin activity.


An observation of thromboxane A2 in arterial blood after cholesterol feeding in rabbits. Agents responsible for the entry of cholesterol-bearing lipoproteins into the arterial wall represent local risk factors in atherogenesis. In an attempt to identify these agents, we inserted a catheter into the ascending aorta of rabbits and 5 ml of arterial blood sample was withdrawn. The contraction of the aortic strip of rabbit against Piper and Vane's antagonists with application of this sample was observed. Samples obtained after feeding of 1 Gm/Kg of cholesterol and after an intravenous administration of thromboxan A2 (TXA2) contracted the aortic strip. Samples from non-treated rabbits or those obtained after intravenous administration of 10 microgram of epinephrine or norepinephrine did not contract the strip. Previous administration of 20 mg/Kg of indomethacin decreased the contraction developed after feeding of 1 Gm/Kg of cholesterol. It was suggested that TXA2 might be released into the arterial blood by the ingestion of cholesterol and might be one of the agents repsonsible for the entry of lipoproteins.


Direct recording of cardiac output- and venous return-curves in the dog heart-lung preparation for a graphical analysis of the effects of cardioactive drugs. The dog heart-lung preparations were prepared. The "equilibrium point", which could be defined as the point at which the cardiac output (CO)-curve and the venous return (VR)-curve crossed, when the CO and VR were plotted against the right atrial pressure, was recorded directly by utilizing an X-Y recorder. The CO-curve was obtained, as a locus of the equilibrium point, by raising and lowering the level of blood in the venous reservoir (competence test). The meaning of the procedure was shown to increase or decrease the mean systemic pressure, and to cause the corresponding parallel shift in the VR-curve. The VR-curve was obtained by changing myocardial contractility. When heart failure was induced by pentobarbital or by chloroform, the equilibrium point shifted downwards to the right, depicting the VR-curve. During development of the failure, the slopes of CO-curves decreased gradually. Effects of cinobufagin and norepinephrine were also analyzed. Utilization of the X-Y recorder enabled us to settle the uniform experimental conditions more easily, and to follow the effects of drugs continuously on a diagram equating the CO- and VR-curves (Gyton's scheme).


Some frontiers in comparative studies of the renin-angiotensin system. A prospective survey on the comparative studies of the renin-angiotensin system (RAS) was made at the final session of the Japan-U.S. Cooperative Seminar, held on November 14--19, 1977, at Jichi Medical School, Tochigi-ken, Japan. Strategies and tactics of the research have been clarified. In morphological studies, the strategy is to clarify structure of the juxtaglomerular apparatus in representative species of vetebrate classes. In chemical studies, each component of the RAS must be established in each vertebrate class. Since we now know the existence of severel new angiotensins in vertebrates, their amino-acid sequences must be determined. They must be synthesized in sufficient purity. It is necessary to establish the international purity and assay criteria for synthetic angiotensins. In comparative studies on physiological aspects, the strategy is to establish the physiological roles of the RAS in vertebrate classes. Controls of blood pressure, of aldostrone secretion, of glomerular filtration rate and tubular transport, and of drinking and intestinal absorpiton are the candidates. Physiological roles of extrarenal renin as well as renal one are interesting. A renin-like substance in the corpuscles of Stannius in the teleosts has been identified preliminarily as hypocalcin. Many frontiers exist in these fields, and one can expect fruitful contributions to research of the cardiovascular disease in humans through comparative studies of the RAS.


Occurrence of the renin-angiotensin system in the vertebrates. The presence and absence of renin activity and juxtaglomerular cells (JGC) in the kidney have been extensively studied among the vertebrates. Renin and JGC have been found in the kidneys of tetrapods  and teleostean fishes. Therefore the renin-angiotensin system probably appeared first during early evolution of teleosts. However, the findings of various investigators need to be analyzed precisely to summarize and the subjects remained for further research need to be pointed out. There still remains a possiblity that a similar hormone is present in the cyclostomes and elasmobranchs. There are some discrepancies between the renal renin activity determined biochemically and the histological visualization of the granules in some primitive bony fishes. There are contradictory reports regarding the presence of macula densa in nonmammalian kidney. The fact that JGC are present extrarenally in sea-horses may suggest some function of this system. Renin-like activity has been reported extra-renally in various mammalian tissues and in the corpuscles of Stannius (CS) in teleosts. Physiological roles of these extrarenal renin have not been clarified. It has been demonstrated that CG contain 'hypocalcin' which lowers plasma Ca level. It is of interest in determining the possible relationship between the renin-angiotensin substances in CS and hypocalcin.


Comparative biochemistry of renins and angiotensins in the vertebrates. Comparative biochemistry of renins and angiotensins was discussed. Renin extracted from hog kidney was different from that from mouse submaxillary glands in immunoreactivity and carbohydrate content. Rat kidney renin was also different from hog kidney renin in the amino acid composition. The presence of big and big-big renins was pointed out immunochemically. These big renins were considered to be precursors of kidney renin. Angiotensins in mammalian and nonmammalian species produced by renal or extrarenal renin have been differentiated by some biochemical and pharmacological criteria. Some of these angiotensins were analyzed sequentially. The replacements of amino acid residues at positions 1, 5, and/or 9 of angiotensin I have been demonstrated in nonmammalian species. Specific pressor activities have been determined using synthetic angiotensins by a 4 point assay in rat. Specific pressor activities of various angiotensins were obtained from the dose-blood pressure-response curves using a single angiotensin sample per assay rat.


Physiological evolution of the renin-angiotensin system. The renin-angiotensin system (RAS) in mammals may participate in the controls of blood pressure and aldosterone secretion, and possibly in the regulation of renal function. It has been shown that renin release is controlled by:1) two intrarenal receptors, the renal arteriolar receptor and the macula densa; 2) the sympathetic nervous system; and 3) several humoral agents. Recent studies indicate interrelations between the RAS and renal prostaglandins and the kallikrein-kinin system. Comparative studies have revealed that renal renin and the juxtaglomerular (JG) cells emerged during the early evolution of bony fishes, wherease the macula densa evolved later in the vertebrate phylogney. Exogenously administered angiotensins and renin produce vasopressor actions in representative species of all vertebrate classes from elasmobranchs to mammals, and increase secreations of mineralocorticoids from the adrenal cortex (interrenal) in amphibians, repitles, and possibly in teleosts. Angiotensin causes glomerular diuresis in teleosts and lung-fishes, which may be ascribed to increased dorsal aortic pressure, while angiotensin may have both glomerular and tubular actions in some amphibians. Intracranial injection of angiotensin stimulates drinking in teleosts, repites, and birds, but not in amphibians. Hemorrage and acute hypotension are potent stimuli for causing renin release in an aglomerular teleost and a bird. When we consider this fact together with the anatomical evidence that the evolution of the JG cells precedes that of the macula densa, it appears that the RAS HAS EVOLVED WITH A CLOSE RELATIONSHIP TO BLOOD PRESSURE HOEMOSTASIS. On the other hand, there is no clear evidence that the RAS is activated in depleted teleosts and amphibians. Although the RAS appears to exert several functions in man and other mammals, some of them may be more important in primitive animals, while a similar function remains in mammals as a relic of the primitive system. Comparative approaches provide a perspective of biological history and unique experimental model that will eventually aid in understanding of the underlying mechanisms operating in mammals.


Congenital aortic regurgitation observed in a thalidomide-deformed child. A case of aortic regurgitation observed in a thalidomide deformed child is presented. Possibility of thalidomide as an etiologic factor was discussed.


Specific inhibition of desmosterol synthesis by ML--236B in mouse LM cells grown in suspension in a lipid-free medium. The suspended growth of LM cells in a lipid-free chemically defined medium was almost completely inhibited in the presence of 0.1 microgram/ml of ML-236B, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate limiting enzyme in cholesterol biosynthesis in mammalian cells. This inhibition was effectively counteracted by adding a small amount of either mevalonate or cholesterol (dispersed in delipidated calf serum) to culture medium. The synthesis of desmosterol, the end product of sterol biosynthesis in LM cells, from [14C]acetate in cultured cells was highly sensitive to ML-236B, being inhibited 35 and 60% at its concentrations of 0.1 and 1 ng/ml, respectively, while the incorporation of [3H]mevalonate into desmosterol was not affected by ML-236B at concentrations up to 0.1 microgram/ml. Synthesis of fatty acids, phospholipids, triglycerides and macromolecules like DNA, RNA and protein were not suppressed by 10 microgram/ml of ML-236B. Desmosterol content of LM cells was reduced by treatment with ML-236B. These results indicate that ML-236B inhibited cell growth via specific interference in the pathway of sterol biosynthesis, presumably on the step catalyzed by HMG-CoA reductase.


Studies on adjuvants for human prophylactics. I. Comparison of efficiencies of different adjuvants at various stages of immunization with tetanus and diphtheria toxoids. Kinetic studies on the adjuvanticities of several substances with different modes of action were performed in guinea pigs by using tetanus and diphtheria toxoids as the antigens. When injected subcutaneously into animals, aluminium, endotoxin, pertussis vaccine and water in oil in water (w/o/w) showed very similar adjuvanticities to tetanus toxoid at the beginning stage of immunization, but the activities except that of aluminium became less significant at later stages after the primary stimulus when antitoxin was produced abundantly. Poly L-lysine and to a less extent poly A:U showed potent adjuvanticities next to that of aluminium throughout the whole immunization period. Combination of poly L-lysine with 0.03 mg aluminium showed a similar adjuvanticity to that of 0.9 mg of aluminium alone. In contrast to rather low adjuvanticities to tetanus toxoid, more distinct adjuvanticities were observed to diphtheria toxoid throughout the whole period of immunization with various substances such as aluminium, poly A:U, w/o/w and poly L-lysine but not with endotoxin.


Studies on the venomous spicules and spines of moth caterpillars. I. Fine structure and development of the venomous spicules of the Euproctis caterpillars. Scanning and transmission electron microscopy (SEM and TEM) revealed unique structures and development of the venomous spicules of tussock moth caterpillars of the genus Euproctis: (1) Flower-like structure at the distal end and a longitudinal minute depression on the proximal subapical wall of these spicules were observed by SEM. This depression was revealed to be a small hole by TEM. (2) During molting, observed were cytoplasmic processes of several trichogen cells penetrating the cytoplasm of a tormogen cell to form the spicules with the holes at their subapical portions. A papilla was formed by a tormogen and several epidermal cells. (3) After the molting, the cytoplasmic process in a spicule disappeared and the spicule cavity was replaced by electron-dense materials secreted apparently from the trichogen cell. (4) It was considered that the electron-dense materials were the main toxic or precursory substances in the Euproctis spicules.


Contractile responses of isolated dog mesenteric arteries to angiotensin I, II and III. The addition of angiotensin (Ang-) I, II and III caused a dose-dependent contraction of helically cut strips of dog mesenteric arteries. Tachyphylaxis developed following repeated additions of angiotensins. Average median effective concentrations of Ang-I, II and III were 3.7, 0.8 and 2.5 X 10(-8) M, respectively. Contractile responses to the angiotensins were attenuated to a similar extent by Ang-II antagonists, Sar1 Ileu8 Ang-II and Sar1 Ala8 Ang-II, but were unaffected by phentolamine, methysergide and diphenhydramine. The response to Ang-I was significantly reduced by treatment with bradykinin-potentiator B, while the response to Ang-II was not influenced. It may be concluded that Ang-I, II and III produce contractions possibly by activation of same Ang-II receptors and that contractions induced by Ang-I are associated, to some extent, with a conversion to Ang-II in the arterial wall.


Strain differences in aspirin-induced gastric ulceration in rats. We found that there are strain differences in aspirin-induced ulceration in pylorus-ligated rats; the ulcer indices varied, from high to low, in the following order: Donryu greater than Sprague-Dawley greater than Wistar. Several experiments including analysis of gastric contents or ionic flux, determination of serum aspirin esterase activity, absorption of aspirin from the stomach, prothrombin time and hexosamine content in gastric mucosa and juice were performed to elucidate the origin of the differences. A significantly higher acid output in Donryu rats, and higher hexosamine content in the gastric mucosa of Wistar rats were noted. However, it appears unlikely that these factors only contribute to the marked strain difference in aspirin-induced ulcers. The possible different sensitivity of gastric mucosal cell itself to aspirin must be considered.


Tryptaminergic mechanism participating in induction of vasoconstriction by adenine nucleotides, adenosine, IMP and inosine in the isolated and blood-perfused hindlimb preparation of the rat. The isolated right hindlimb of the recipient rat was perfused at a constant flow rate through the femoral artery with heparinized blood from the carotid artery of a donor. The preparations were under a 99.0 +/- 0.8 mmHg of mean perfusion pressure (N = 63) and 3.3 +/- 0.1 ml/min of blood flow through the right femoral artery. The actions of adenosine, adenosine tri-, die- and monophosphate, inosine monophosphate and inosine on the femoral vascular bed were investigated, respectively. These substances injected into the femoral artery, with the exception of inosine, caused a dose-dependent vasoconstriction always preceded by a temporal vasodilatation. Inosine induced only a prompt vasoconstriction. The vasoconstrictor responses to these substances were diminished or reverted to vasodilator ones after repeated administrations and such were significantly prevented by pretreatment with either reserpine or methysergide. These results indicate that all the purines tested induce a vasoconstriction in the femoral vascular bed of the rat through a common (tryptaminergic) mechanism and that such seem to be potent releasers of 5-hydroxytryptamine from peripheral tryptaminergic storage sites.


Role of gastric motility in development of stress-induced gastric lesions of rats. Gastric motility of stressed rats was studied to determine its role in producing stress-induced gastric lesions. Restraint and water immersion resulted in an increase in gastric motility which consisted of an increase in frequency and amplitude of contractions and a rise in gastric tone. This increase reached maximal levels 2 to 4 hr after stress, and persisted thereafter. Formation of gastric lesions was markedly accelerated after occurrence of the increased gastric motility. In contrast, restraint alone neither produced such a vigorous increase in gastric motility, nor were the gastric lesions severe. A continuous infusion of papaverine during restraint and water immersion inhibited increase in frequency and amplitude of gastric contractions and prevented formation of gastric lesions. It is concluded that increased gastric motility is closely associated with marked formation of gastric lesions under conditions of restraint and water immersion stress and is probably a main cause for their vigorous formation, although formation of lesions occurs to a small degree without involvement of gastric motility.


Antihypertensive effect of trichlormethiazide in spontaneously hypertensive rats. Antihypertensive and diuretic effects of trichlormethiazide (TCM) were investigated in the spontaneously hypertensive rats (SHR). The antihypertensive effect of TCM in an acute experiment was observed in male SHR only at a dose over 10 mg/kg given intraperitoneally and not in female SHR and normotensive Kyoto Wistar rats. In a subacute experiment (6 weeks), TCM retarded the development of hypertension in the male SHR loaded with 1% saline solution at an oral dose over 1 mg kg-1 day-1 and such had a diuretic effect. Oral administration of TCM and hydrochlorothiazide (HCT) at 10 mg kg-1 day-1 retarded the development of hypertension in the saline loaded female SHR to the same degree, but the relationship between antihypertensive and diuretic effects of both compounds was obscure. Except for decreases of water contents in the thoracic artery and wet weights of hearts, the electrolyte, uric acid, catecholamine and 5-hydroxytryptamine contents in the serum or/and organs were not affected by either TCM or HCT. It is concluded that the antihypertensive effect of TCM and HCT can be observed in SHR with a saline-load, and that the effect may be due to diuretic actions in the male. The relationship was not apparent in female SHR.


Pathophysiology and management of acute gastric mucosal hemorrhage. Unlike hemorrhage from peptic ulcer, surgical management for hemorrhage from stress ulcer is not necessarily successful on many occasions. Thus, the most important thing one can try is to prevent the development of this condition. Forty eight patients admitted to the Shock and Trauma Unit, Hahnemann Medical College and Hospital, who had a primary diagnosis of shock were divided into three groups: group 1 received the standard shock regimen plus large dose steroid therapy repeated every four hours for 36 hours; group 2 received the standard shock regimen plus small dose steroid therapy repeated every four hours for 96 hours; group 3 received the standard shock regimen without the addition of steroids. There was a 57.9 per cent incidence of acute gastric ulceration in those shock patients not treated with steroids (group 3) compared with 33.3 per cent incidence of gastric ulceration in group 2 and 5.9 per cent incidence in group 1. The use of pharmacologic doses of steroids early in the shock state for period of less than 36 hours seems to reduce the incidence of gastric ulceration and hemorrhage in low flow states associated with septic, cardiogenic and hemorrhagic shock.


A new bubble oxygenator (OCVC oxygenator): development and clinical application. A new bubble oxygenator, designed for simple operation and clinical efficacy in intracardiac surgery, has been developed and clinically evaluated. This device is characterized by an oxygenating chamber with controllable blood-volume, integral heat exchanger and two-stage microfilter of gravity drainage system, an apparatus for creating and uniformly distributing oxygen bubbles, and construction materials of the device known to be minimally traumatic to the blood. Clinical experience in 132 infantile and pediatric open heart procedures has demonstrated its effectiveness as measured by embolic complications and simplicity in maintaining physiologic blood gas levels.


Use of intra-aortic balloon pumping (IABP) in clinical cardiac surgery and management of patients with IABP. One hundred thirty eight patients were reviewed which required IABP assist. Sixty nine (84 per cent) of 82 patients who had been able to come off cardiopulmonary bypass despite increasing pharmacologic support survived operation and 56 patients (68 per cent) discharged hospital. Twenty three (75 per cent) of 31 patients who took for elective coronary artery surgery as extremely high risk because of extensive three vessel coronary artery disease and severely compromised left ventricular function discharged hospital. In summary, hospital death was 35 per cent, late death 12 per cent and long term survivors 54 per cent. Severe complication concerned with inserting balloon catheter occurred in two cases (1.4 per cent) which were abdominal aortic dissection and laceration of iliac artery. At the present time, the primary indication for IABP is in assistance of the open heart surgical patient. Thre are three important factors in successfully managing the patients with IABP. First, begin IABP assist as soon as possible if indicated. Second, keep an adequate circulating volume with mean left atrial pressure being maintained around 20 mmHg and cardiac index at 2.1 L/min./M or greater. Third, improve the peripheral vascular circulation, which might need peripheral vasodilator.


Relation of stroke and cardiac indices to serum catecholamines following open heart surgery. Serum catecholamines (epinephrine, dopamine and norepinephrine) were measured two, four and six hours after open heart surgery. The ratios of stroke index (SI) and cardiac index (CI) to catecholamines (CA) were determined. Patients studied consisted of 27 with congenital and 14 with acquired heart disease. Extracorporeal circulation (ECC) time was longer than 90 minutes in 17 and shorter in 24 patients. SI and CI diminished in elder patients with congenital disease (Group Cg-ad), patients with acquired disease (Group Ac) and patients with a longer ECC time (Group L). Therefore, elder age and/or longer ECC time seems to be responsible to the lower indices. However, the ratios of the indices to CA showed that the lower indices indicated the poor response of the myocardium to CA in Group Ac and Group L. The response was larger in Group Cg-ad and the lower indices were related to lower serum CA level. It was concluded, therefore, that the indices of stroke volume and cardiac output had inverse correlation to ECC time, but not to age, namely, prolonged ECC compromised more severely the myocardium and resulted in the poor response of the myocardium to CA. Subsequently, to compensate for the poor response, serum CA levels were elevated probably to maintain due SI and CI in patients with prolonged ECC.


Immunological responsiveness and adjunct immunotherapy in lung cancer. Immunocompetency was assessed before and after the operation in 40 patients with lung cancer by skin reaction against tuberculin (PPD) and dinitrochlorobenzene (DNCB), lymphocyte response to PHA, proportion of T-cells, macrophage migration inhibition test (MIT) and the presence of blocking factor. MIT was positive in 27 per cent and blocking factor was positive in 42 per cent. Immune response paralleled the clinical stage of the lesion. In curative resection cases, the immune response rose postoperatively, but declined in non-resectable or recurrent cases. The influence of postoperative radiation therapy, cancer chemotherapy and host mediated agents on the patients was observed. The feasibility of adjuvant specific immunotherapy is discussed.


Chronologic comparison of postoperative results in gastric cancer surgery. Patients who underwent gastric cancer surgery in our clinic during a 12-year period from 1960--1971 were divided into two groups. Group A is comprised of patients who were treated in the first, and group B of patients treated in the second half of this 12-year period and the short- and long-term results were evaluated and compared for both groups. We discovered that both short- and long-term results were better in group B than in group A. Group B contained more cases of histologically early cancer stages and extensive lymph node resection was performed more frequently in group B than in group A. These factors may account for the better results obtained for group B. In addition, performance of gastrectomy combined with the resection of other neighboring organs may have effected the better long-term results observed in group B.


Precancerous lesions of the colon and rectum. Fourty-six cases of polyps and polypoid lesions of the colon and rectum were operated at the First Department of Surgery, Gifu University School of Medicine during the last 16 years. Polyps were classified into five groups according to their degree of atypicality and the relationship between polyps and cancer was investigated. The adenomatous polyps were prone to become malignant and it appears that the larger the polyp size, the greater the incidence of severe atypia and the greater the polyps' malignant potentiality. The malignant polyps developed more frequently in the distal colon and rectum than in other parts. Focal and invasive cancers limited to the submucosal layer were found exclusively in the sigmoid colon and rectum.


Degenerative changes of vein grafts in preparation media: preliminary studies by electron microscopy and fibrinolytic autography. Degenerative changes of saphenous vein grafts in four preparation media (heparinized whole blood at room temperature and 4 degrees C, and heparinized normal saline at same temperatures) were examined by scanning and transmission electron microscopy and fibrinolytic autography. Following 60--90 min. storage in heparinized normal saline at room temperature, marked morphological changes were present in the media, accompanied by swelling of the endothelial cells, however the tunica media and adventitia were well preserved even after 120 minutes in all of the four preparation media. The decrease in fibrinolytic activity was comparable to the observed morphological changes. In heparinized whole blood at 4 degrees C, degenerative changes were slow and mostly of a slight nature.


Effect of perfluorochemical (PFC) emulsion on acute carbon monoxide poisoning in rats. The effect of perfluorochemical (PFC) emulsion (25 w/v per cent of PFC concentration) on carbon monoxide poisoning was studied in rats exposed to 97 per cent O2 and three per cent CO. There was no significant difference in conversion rate of hemoglobin to carboxyhemoglobin (COHb) between PFC emulsion and saline groups. However, after re-exposure to pure oxygen, PFC emulsion group circulation reconverted to oxyhemoglobin (OXYHb) at a significantly faster rate than circulation in the control group. Survival time of rats was considerably affected by infusion of PFC emulsion and prolonged in proportion to increased injection dosage. Significant elevations in plasma glucose, lactate and aldolase levels and lactate/pyruvate ratio were found in the saline group and these levels remained well within normal range in the PFC emulsion group. These results indicate that PFC emulsion can function as an oxygen carrier in the presence of carbon monoxide and can deliver sufficient oxygen to peripheral tissues.


[Capillary blood circulation in middle-aged and elderly arterial hypertension patients]. Eighty patients with hypertensive disease and sixty patients with atherosclerotic (systolic) hypertension of the elderly (60--70 years old) and old (78--89 years old) age groups were examined. Skin capillary circulation and the indices of central hemodynamics were studied. It was found that changes in capillary circulation in elderly and old patients with hypertensive disease or systolic hypertension had no specific features and were of the same character as those in healthy individuals of the same age. In decrease of arterial pressure as the result of diminished cardiac output deterioration of capillary circulation was quite frequently encountered. A hypotensive effect, which is attended with reduction of total peripheral resistance, leads as a rule to improvement of capillary circulation.


[Hormonal regulation of the heart in aging]. It was established in experiments on adult (8--12 month) and old (26--32 month) rats that in ageing the sensitivity of the cardiovascular system to certain hormones--adrenaline, vasopressin, insulin, thyroxine, estradiol dipropionate--grows while its reactivity to them diminishes. The administration of these hormones causes significant changes in hemodynamics and myocardial contractility. Adrenaline and thyroxine lead to an increase in the blood minute and stroke volume, arterial pressure, cardiac index and left ventricular work index, maximum rate of intraventricular pressure growth, maximum rate of myocardial fiber shortening, and in the contrastility index. Vasopressin and insulin cause a decrease in the indices of general hemodynamics. The increased sensitivity of the heart to hormones at old age and diminution of its reactivity lead to prolonged, protracted reactions of the cardiovascular system in elderly and old individuals.


[Hormones in ischemic heart disease with the presence of coronary atherosclerosis]. The activity of the pituitary hormones (ACTH, STH, TTH, FSH, LH), the adrenal hormones (cortisol, aldosterone), the kidney hormone (renin), and the thyroid hormones (thyroxine tri-iodthyronine), the thyroxine binding capacity of blood proteins and the activity of the hormones of the pancreas (insulin) and the sex glands (testosterone, estradiol) were studied in 26 males suffering from ischemic heart disease verified by means of selective coronarography and in 20 healthy males with no atherosclerosis of the coronary arteries of the heart. Patients with ischemic heart disease were found to be marked by increased activity in the blood of ACTH, TTH, cortisol, aldosterone, insulin, and estradiol and reduced concentration of STH, thyroxine, and testosterone. These shifts in the activity of the hypothalamo-hypophyseal system and in its subordinate hormonal systems play an important role in the origin of the atherosclerotic process and assosiated ischemic heart disease.


[Evaluation of myocardial contractile function in chronic postinfarct cardiac aneurysm]. The ventriculograms of patients with chronic postinfarction aneurysm of the heart were studied with the use of separate analysis of the contraction indices of the functioning and non-functioning parts of the left ventricular myocardium. Relatively high indices of the ejection fraction of the functioning part of the myocardium with low indices of the total ejection fraction were noted. A correlative dependence was found between the total ejection fraction and the ratio of the volumes of the nonfunctioning part of the myocardium during systole and diastole to the total volume of the left ventricle during the same phases, which is evidence that these indices are important in appraising myocardial contractile function in aneurysm of the heart.


[Coronary bed in aneurysm of the left ventricle]. Clinical and radiologic examination, including selective coronarography and catheterization of the cardiac cavities, was carried out in 110 patients with post-infarction aneurysm of the left ventricle. Three groups of patients were distinguished: patients with affection of one of the major cardiac arteries (44), those with affection of two coronary arteries (32) and patients with affection of three arteries (32). Two patients had no stenosis of the coronary arteries, The anterior interventricular artery was occluded in 95,8% of patients. Operation for aorticocoronary shunt to the artery in the zone of which the arteries were located proved impossible in 65% of patients. Other arteries with no aneurysms in their channels contribute to the formation of collateral circulation and form a network of anastomoses at the boundary with the heart aneurysm and in this improve the nutrition of the healthy part of the myocardium experiencing an additional load. In stenosis of these arteries, the creation of an aorticocoronary shunt is expedient.


[Discharge energy and the problems of anesthesia in the electrical cardioversion of paroxysmal arrhythmias]. The efficacy of electroimpulsive therapy with low energy discharges (up to 50 joules) in various paroxysmal arrhythmias was studied. A mild tranquilizer, seduxen (diazenam), was used as the anesthetic. Electroimpulsive therapy with low-energy discharges was found to produce a high effect in ventricular tachycardia and atrial flutter but a poor restorative effect in atrial fibrillation. The possibility of successful anesthesia with seduxen in electrical cardioversion of paroxysmal disorders of cardiac rhythm is concretized.


[Echocardiography in the diagnosis of tetralogy of Fallot]. Echocardiography was performed in the examination of 35 patients with tetralogy of Fallot and 3 patients with pentalogy of Fallot. The echocardiogram demonstrated dextrodivision of the aortic root, interruption in the continuity of the interventricular septum and the anterior wall of the aorta, incomplete image of the interventricular septum in its upper part, distention of the aortic root, stenosis of the right ventricular infundibulum, and hypertrophy of the right ventricular myocardium. The presence and severity of all developmental anomalies of the heart and major vessels known as tatraology of Fallot may be identified by the echocardiography method in most cases.


[Effect of short-term antiorthostatic hypokinesia on the central and intracardiac hemodynamics and metabolism in a healthy human being]. The right parts of the heart and the radial artery were catheterized in healthy male volunteers before and 5 days after strict bed rest in antiorthostatic position of the body (-4.5 degrees) After immobilization most values of central circulation showed no essential changes; the only exception were indices characterizing the inotropic myocardial condition. A shift in the direction of acidosis of a mixed character was noted in mixed venous blood, the beta-lipoprotein content increased. A decrease in the arteriovenous difference in oxygen was encountered in blood draining from the heart (from the coronary sinus).


[Personality characteristics of patients with the cardiac type of neurocirculatory dystonia]. The state of the psyche was studied in 128 patients with cardiac-type neurocirculator dystonia. The results of clinical examination and the Minnesota test (MMT) showed that with the increase of the subjective manifestations of the cardiac pain syndrome and extension of the zones of pain sense disorders in the left half of the chest, a clear tendency to an increase of the neurotic changes was revealed, which were found, respectively, in 61.9, 89,7 and 100% of patients examined with grade I, grade II and grade III cardialgia. The psychic disorders were predominantly of the hysterical and hypochondriac types, which should be borne in mind when prescribing treatment.


[Effect of swimming on the uptake and content of taurine in the rat heart]. 14C-taurine uptake and total taurine content increase during a 15-min period of swimming. Prolongation of this period leads to more active taurine metabolism (ISA formation) but the total taurine content does not change. Active accumulation against its concentration gradient and maintenance of the taurine content at the same level during the entire period of swimming suggest that the taurine uptake and its metabolism are interdependent and very important for heart activity.


[Disturbance of the intracellular calcium distribution in the fatty tissue of rats with spontaneous genetic hypertension]. The presence of three pools of exchangeable calcium (A,B and C) was demonstrated by the method of investigating the kinetics of 45Ca efflux from the fat issue of rats; the two most slowly exchangeable pools (B and C) reflected the distribution of intracellular calcium. The calcium content in the pools B and C of the fat tissue of rats with spontaneous hypertension was increased by 71 and 29%, respectively, as compared to that in the normotensive controls. Adrenalectomy leads to a marked redistribution of intracellular calcium, but the differences between spontaneously hypertensive rats and normotensive rats in the calcium content in the pools B and C are nonetheless maintained. These differences in the distribution of intracellular calcium may be the direct cause of the change in the hormonal sensitivity of the adipocytes of rats with spontaneous genetic hypertension.


[Change in the reactions of isolated vascular segments under the action of hypotensive agents]. It was shown that reactions of isolated vascular segments to electric stimulation changed in character under the effect of reserpine, ornid, benzanidine, and aldomet. Replacement of contraction by relaxation is characteristic of all hypotensive agents. This is revealed on preparations which respond initially by equivocal reactions (relaxation and contraction) depending on the intensity of the stimulation. The replacement of the sign of the reaction is marked by certain peculiarities in the case of each agent. The possibility of contraction is maintained only in response to a high dose of stimulation on condition that benzanidine and aldomet are administered. Under the effect of reserpine and ornid, initially unequivocal reactions are replaced at first by two-phase reactions (contraction then relaxation) and then by single phase (relaxation); under the effect of benzanidine and aldomet they are sharply weakened.


Energy and protein intakes as determinants of nitrogen balance. Changes in caloric intake below or above energy needs affect nitrogen balance, so that any change in caloric intake results in a corresponding alteration in nitrogen balance. The improvement in nitrogen balance caused by an increase in energy intake, however, can be frustrated if intake of protein is inadequate; conversely, the beneficial effects of an increase in protein intake can be inhibited by an inadequate energy intake. These observations mean that, in experimental studies, nitrogen balance is the result of levels of both energy and protein; in consequence, protein requirements can be interpreted only from such studies, where energy intake is also defined under the experimental conditions. In addition to the effect of dietary energy supply, dietary carbohydrate has a short-term specific effect on protein metabolism not shared by fat, in which plasma amino acids are diverted into muscle protein through the action of insulin released by the dietary carbohydrate. This metabolic interaction also occurs between carbohydrate and amino acids absorbed from the same meal.


Effect of essential amino acid supplementation on muscle and plasma free amino acids in chronic uremia. In chronic uremia patients on an 18-g protein diet for 2 to 3 weeks, the intracellular free amino acid pattern in muscle was grossly abnormal, with low concentrations of threonine, valine, carnosine, and high concentrations of aspartate, glutamine, glycine, alanine, and taurine. When the protein-poor diet was supplemented with essential amino acids (2 to 3 times that for minimum requirements) and histidine, these abnormalities were partly corrected. Other abnormalities, however, were observed, such as low intracellular concentrations of phenylalanine and tyrosine, and high concentrations of lysine, histidine, ornithine, and citrulline.


[Scotoma in the binocular field of vision in severe amblyopia and microstrabismus (author's transl)]. Binocular perimetry with Aulhorn's Phase difference haploscope is described. Of 62 patients with primary micro-squint, 21 patients showed no scotoma, 15 patients showed a fixation or zero point scotoma of 0.5-1 degrees, 26 patients showed a larger scotoma (average: 3.7 degrees). In addition, 15 patients with larger angle and deep amblyopia were examined. The scotoma average was 8.8 degrees. A zero point scotoma was always present, whereas the central foveal scotoma was often missing.


[Temporal change of the disc in normal adults (author's transl)]. We have recently proposed a procedure called stereochronoscopy which allows the detection of temporal changes in the disc by stereoscopic observation of exactly centered fundus pictures. We show that this procedure can also be applied in a slightly modified form to fundus pictures that are not specially centered, although with less precision. Using this technique we were able to show on material covering 10 years (50 eyes) that the discs of healthy adults do not as a rule change over a period of at least 8 years. This is valid for observation of the pictures with an overall magnification of X 14.


[Meandering of retinal arteries from pulse wave: a stereochronoscopic study (author's transl)]. In a case of aortic insufficiency, increased snaking occured with very pulse wave coming through the retinal arteries. When photographs taken at diastolic and systolic culminations were compared, with the haploscope, when stereoscopically seen, they clearly showed the subtile deformation of the vessels under a stereoscopic effect.


[Haemodynamics in retinal branch vein obstruction (author's transl)]. A branch vein obstruction in a 44-years-old woman recovered with in 7 months without any clinical residuals. The evaluation of fluorescein angiograms performed during thrombosis and after recovery showed significantly reduced retinal circulation times in around the thrombosis. The results indicate an increased blood flow ranging between 50 and 200% around the obstructed area of the retina. The haemodynamic situation of the retinal circulation during branch vein obstruction and its therapeutic consequences (photocoagulation) are discussed.


[Fluorescence angiography in retinal detachment (author's transl)]. Fluorescence angiography was performed in 11 patients, suffering from retinal detachment, and in 17 patients after various successful retinal surgery. The preoperative findings showed an obscured background fluorescence by the subretinal fluid in the detachment area, and various circulatory disturbances in the vicinity of the retinal equatorial degenerations, holes and tears. The absent fluorescein extravasation into the subretinal fluid gives evidence against the participation of the choroid in the formation of the subretinal fluid. The postoperative findings demonstrated that from various operations episcleral buckling with kryopexy is accompanied by the lowest fluorescein extravasation and from the fluoroangiographic point of view, it appears as the less injuring operation.


[Retinal thromboses with metabolic disturbances (author's transl)]. In 31 out of 35 patients with retinal thromboses metabolic disturbances were found. 11 patients showed disturbances of lipid, purine and carbohydrate metabolism and hypertension. In 19 further cases hyperuricaemia was found, usually combined with hypotriglyceridaemia. Two young women with branch vein thrombosis and pathological metabolic values were taking hormonal contraceptives. The possible relationships between vein thromboses and metabolic disturbances are discussed.


[Early defects in the visual field in glaucoma (author's transl)]. This study shows that the field defects in simple glaucoma can occur as paracentral scotoma (77%) as well as nasal skip defects (20%) in the central or peripheral field. Also a combination (54%) of both defects is already possible at the start. This points out that more than one nerve bundle can be affected either simultaneously or one shortly after the other. It was also remarkable that by Drance's modification of Armaly's method for two eyes a typical nasal skip and/or a paracentral scotoma with temporal visual field defect occurred as the first sign.


[Malignant glaucoma (author's transl)].

[Malignant glaucoma (author's transl)]. A 35-year-old male, one of three siblings with spherophakia and glaucoma, was treated surgically by aspiration of vitreous through a posterior sclerotomy wound, and air insufflation of the anterior chamber in each eye. Previous peripheral or sector iridectomies were not helpful in contolling the condition. Some improvement was noted with intensive cycloplegic therapy in each eye. In the right eye, one surgical procedure was sufficient to arrest the condition. In the left eye, a sector iridectomy, and three posterior sclerotomies combined with air insufflations of the anterior chamber have been unsuccessful in controlling the pressure. A further sclerotomy with a vitrectomy instrument to remove most of the formed vitreous followed by air insufflation of the anterior chamber is proposed for the uncontrolled eye and if this is not successful in controlling the condition, lens extraction will be carried out.


[Are functional disturbances in chronic simple glaucoma indispensable for carrying out a covered sclerectomy operation? (author's transl)]. The existence of functional disturbances in chronic simple glaucoma is generally considered to be an indispensable prerequisite in deciding to perform a glaucoma operation. The favorable results obtained with the covered sclerectomies and their small percentage of postoperative complications have encouraged the authors to prefer operative treatment over conservative magangement more often in chronic simple glaucoma. The decision between operative and conservative management does not however depend solely on the existence of visual field defects. It also depends on the social status of the patient, poor drug tolerance and other factors as well.


[Trabeculotomy and cataract-extraction: simultaneously or step by step? (author's transl)]. In 64 eyes the combined procedure (group I) and in 67 aphacic eyes a trabeculotomy (group II) was performed. There were different types of glaucoma. Re-examinations wer done 6 months and 1--10 years postoperatively. No definite differences of operative or postoperative complications existed between the two groups. In eyes suffering from primary open angle glaucoma intraocular pressure was controlled in 65--91% in both groups. In group I visual acuity was slightly better. On the other hand in these eyes more often a deterioration of the visual field was observed inspite of i. o. pressure not exceeding 21 mm Hg with a single exception. In group II further glaucoma surgery was necessary in more eyes than in group I.


[Filtering blebs after cataract extraction (author's transl)]. Filtering blebs following cataract extraction with a limbus based flap may occur approximately 2 to 3% of the time. Difficulty with wearing of contact lens may ensue, the likelihood of infection with postoperative endophthalmitis is remote. A technique for repair by excision of the bleb with a sliding conjunctival flap is described. The results in five patients are reported.


[Keratotorus. Aetiology with regard to heredity (author's transl)]. We describe the biggest group of toric deformation of the cornea reported up to now. We point out in particular two ribs whose parents are blood-related. Hence we obtained the first evidence for an inheritance (autosomal recessive) of this corneal anomaly. The term Keratotorus is recommended as the best definition for this toric corneal deformation. Although there are similarities with other anomalies of curvature of the cornea, the clinical picture of keratotorus can be seen also in the future as a nosological entity.


[The significance of the scleral flap for the surgery of glaucoma (author's transl)]. The importance of the scleral flap used in the covered fistulising operations is reported. The authors describe in detail significant observations contributing to the successful outcome of these operations. They make the hypothesis, supported by their microsurgical observations, for the formation of a slit-like space under the scleral flap, named "Parathalamus", which is an extension of the anterior chamber. This space communicates with the anterior chamber through the trephination hole. The aquous humor flows to the subconjunctival space through a fine membraneous tissue, formed on the surface of the lips of the "parathalamus".


[About experiences with goniotrepanation (Elliot-Fronimopoulos) (author's transl)]. We report about the results of our patients operated with goniotrepanation (Elliot-Fronimopoulos) in the years from 1975 till 1977. During these 3 years 101 eyes were operated and 80 eyes could be reexamined between 6 and 36 months following operation.


[Results of a combined glaucoma- and cataract-operation (author's transl)]. 106 eyes with glaucoma and cataract have been operated simultaneously with a combined cataract-extraction (cryoextraction) and trephining with scleral flap (Elliot-Fronimopoulos). In 95 eyes intraocular pressure was compensated without local therapy (about 90%).


[Results of the ciliary body exposure (CBE) in secondary angle closure glaucomas. 1. A clinical study (author's transl)]. The authors present their clinical results of the ciliary body exposure following Benedikt and Hiti. This technique has been performed in 23 patients suffering from secondary angle closure glaucoma. As far as the intraocular tension is concerned good results have been obtained in nearly half of the patients. The results are compared with those of other surgical techniques against secondary angle closure glaucomas.


[Results of the ciliary body exposure (CBE) in secondary angle closure glaucomas. 2. A histological study (author's transl)]. After treatment of secondary angle closure glaucomas by ciliary body exposure with lamellar scleral resection five eyes had to be enucleated. In view of the histological findings taken from these eyes mode of action and therapeutic value of this operation are considered. The effectiveness of scleral resection seems to be doubtful and there is evidence that permanent regulation of intraocular tension depends mainly on direct diathermy of the ciliary body.


[Problems of the cutaneous malignant melanoma near the eye (author's transl)]. A description is given of a cutaneous malignant melanoma in the region of the lid angle with involvement of the upper and lower lid and the tarsal and bulbal conjunctiva.


[Conjunctivitis lignosa -- an autoimmunity disease (author's transl)]. In a 33-year-old patient discrete conjunctivitides occured over a period of 3 years. Grey-white, fibrinous, spongy conjunctival swellings and white areas of cartilage-like consistency occured in relation with these. Microscopically these lesions showed parakeratotic cornified stratified epithelium, leukoplakias, chronic inflammation, round cell infiltrates, and vessel sprouts. Immunofluorescence showed, in the preparations incubated with antihuman compliment (C3), what could be described as characteristic for allergic vasculitis.


[Fungal growth on soft contact lenses (author's transl)]. The relevance of fungal contamination of soft contact lenses is demonstrated by own clinical observations in 25 cases. It can be shown by surface-microscopical, histological and mycological analysis, that various fungi can not only grow on the surface of HEMA-lenses, but can also invade the material. The efficacy of chemical disinfectants, as tested against two of the isolated fungi seems to be inferior to that of heat sterilisation. The resulting fundamentally and clinically important consequences, especially concerning permanent wear of hydrophilic contact lenses, are discussed.


[Pupil and light sense perimetry with light and dark adaptation (author's transl)]. In comparison to light sense perimetry the use of pupillomotoric thresholds determination in the central region of the retina at various visual field illumination (10 asb, 0,1 asb, 0,001 asb, 45 degrees Meridian, 27' testpoint) has yielded the following results: 1. The maximum of the pupillomotoric sensitivity profile lies independant of the state of adaptation in the fovea. 2. Irrespective of adaptation state the course of the pupillographic profile curves are congruent. 3. Sensoric determinations show a slow flattening of the curves to the periphery whereas comparatively pupillographic determination yields a steep course (difference in areal summation). 4. In total the pupillomotoric sensitivity increases only about 10 db during the change of adaptation from light to dark. --As the phasic pupillo-light-reflex is elicited by rods and cones the differences between the sensoric and pupillomotoric threshold determinations must arise from intraretinal neuronal processes and not from the receptor reactions.


[The importance of the interference fringe visual acuity in the indication of a cataract-extraction (author's transl)]. 100 patients have been examined before and after cataract-extraction using the Retinal Visual Acuity Tester, Takata, Japan. Laser produced interference fringes are formed on the retina, as a result the visual acuity can be determined easily before the operation. -- With immature cataracts we obtained a good correlation between the preoperative interference fringe visual acuity and the postoperative visual acuity tested by Landoltrings. Therefore, it can be differentiated whether worse visual acuity is caused by the cataract or by a retinal disease.


[Measuring the breath of fusion in reduced monocular and binocular visual acuity (author's transl)]. The range of fusion was measured with the synoptophore with different objects in 100 students. The visual acuity of the tested persons was reduced monocularly and binocularly by fogging occluders. The range of fusion decreases more strongly in the case of monocularly reduced vision than in the case of binocularly reduced vision to the same degree. Therefore it is not the absolute value of the reduced vision which is responsible for the decrease in the range of fusion but rather the difference between the visual acuity of both eyes. This result is important for the therapy with fogging occluders, prism foils and penalisation methods.


[The A and V phenomenon and squint operations (author's transl)]. In 140 cases with strabismus of early onset the change of a A or V pattern was examined after a weakening procedure of the oblique muscles or a vertical transposition of the horizontal rectus muscles of one eye was done. The horizontal incomitance was measured between up and down gaze of 20 degrees. In cases with pronounced overaction of the oblique muscles we performed a recession of the inferior oblique or a tenotomy of the superior oblique respectively. If there was no significant vertical deviation we combined the recession- resection procedure with a vertical transposition of 4 to 50 mm. 75% of all cases showed a reduction of the incomitance (3 degrees or more). In average the preoperative pattern was reduced 70%. The most effective procedure was the bilateral superior oblique tenotomy, and the weakest the vertical transposition against the A- pattern.--In 95 cases with a A or V pattern only a horizontal recession-resection procedure was done. 38% showed a change of the preoperative incomitance but the average reduction was under 2%.


["Kestenbaum's surgical rotation of the eyes" in patients with head tipped to the shoulder (author's transl)]. The principle of Kestenbaum's surgical rotation of the eyes has been found applicable to cases with head tilt to the shoulder. With restriction to the anterior parts of the obliques, which are acting mainly rotatory, the authors were able to release 9 patients out of 25 from their abnormal head posture with their operation. 12 showed definite improvement. However, the pathophysiology and the abolition of the head tilt to the shoulder could not alltogether be explained yet. Latent nystagmus with a resting position is found in only two out of three, a rotatory component only in one out of three patients. The authors believe that the picture of head tilt to the shoulder may rather be located within the classification of congenital strabismus syndrome (Lang) than within a strict causal classification after a certain type of nystagmus.


[Specular microscopy of the corneal endothelium (author's transl)]. Specular microscopy enables the examination of the endothelium of the isolated and perfused cornea. It is of great help in evaluating donor material in an Eye Bank. The in vivo observation and microphotography of the corneal endothelium makes it possible to detect early degenerative, traumatic surgical and other pathological changes of the monolayer.


[Controlled suction in vitrectomy (author's transl)]. A peristaltic pump (type "Perpex", J. H. Guldener, Zürich, Switzerland) was modified for controlled aspiration in vitrectomy (fig. 1). The surgeon operates start, instantaneous stop and back flush with a single foot pedal. Suction and cutting device are controlled independently. Suction flow can continuously be varied between 0 and 16 ml/min (fig. 2). This less critical function is operated by the assistent. The upper limit of suction flow depends on infusion resistance and preselected differential pressure (fig. 3). The infusion resistance and its reciprocal, the inflow rate, vary considerably with different instruments. In four devices infusion resistance was measured and found to vary by a factor of up to 4.6. Low infusion resistance allows high suction flow and thus shorter operation time for certain conditions such as "ochre membranes" or intrasurgical bleedings. Further aids which we use in combination with a Zeiss OPMI-8 are an intense external xenon light source for variable slit illumination which makes the use of intravitreal fiber optics unnecessary, and a mirror combination to achieve an 11 degrees semi-coaxial stereoscopic view of the operation field for the assistent.


[Improved rapid sequence fluorescein angiography for retinal circulation studies (author's transl)]. Investigations of the initial phase of the angiogram and measurements of retinal circulation times require a rapid sequence angiography. Although almost all of the available cameras allow for 2 or 3 exposures per second, such rapid sequence angiograms are not performed routinely. Especially the patient's stress from 2 or 3 flashes per second is considerable making these investigations very difficult. We have introduced 3 modifications of the regular technique of rapid sequence angiography that greatly facilitate the procedure so that large numbers of patients can easily be investigated in clinical routine. 1. The regular fixation target in the Zeiss fundus camera has been replaced by a special diaphragm (Fig. 1) which will exclude part of the fundus from exposure to light. This way pictures are taken only of the disc and the peripapillary area which are most important for circulation studies. After completion of the rapid sequence the diaphragm can easily be removed and further pictures taken of regular size. 2. The fluorescein is injected by means of an automatic injector (Fig. 2) in order to obtain a concentrated dye bolus. 3. The sequence of the angiogram is controlled by an electronic timer (Fig. 3 a and b). The photographer can thus fully concentrate on the camera adjustment without worrying about dye injection or triggering the camera. The perfect standardisation obtained will facilitate the measurement of different circulation parameters later on the film.


[Retinal circulation times as determined by fluorescein angiography (author's transl)]. Using a standardized technique of rapid fluorescein angiography applying a special diaphragm in the camera to reduce the patient stress by the frequent flashes and an automatic dye injection retinal circulation times of 173 healthy eyes were measured and statistically analysed. Circulation time was defined as the time interval between first visible arterial and venous fluorescence of corresponding vessels near the disc margin. The circulation time for the temporal vessels (1.1--1.2 s) was significantly faster than that of the nasal vessels (1.3 s) whereas there was no significant difference between the upper and lower main vessels. The very short circulation times are caused by short circuits near the disc. The difference between the shorter temporal and longer nasal times is caused by the macular circulation. It would therefore be more accurate to speak of peripapillary circulation times or of circulation times of the posterior pole of the fundus.


[Bilateral vascular papillitis following ergotamin medication (author's transl)]. A 36-years aged woman suffering from migraine used Ergosanol special-suppositories. An edema of the retina with star figure appeared in both eyes with only a few months distance. After putting away that drug visual acuity restituted completely in spite of a partial neuritic atrophy of the optic nerve in the first suffering eye. If Ergotamin containing drugs are not used for too long time the condition usually is getting better within a few days. Thereby the diagnosis can be confirmed clinically. The same results could be expected if DHE leads to Ergotismus which is not yet confirmed. In literature central scotomas as well as annular scotomas are reported. In Ergotamin induced angioneuropathies there is a large difference in individual response. Our observation showed that drugs taken for years are no more felt as a pharmacon by a patient and therefore are not reported to the examinating physician.


[Operations and occlusion treatment in unilateral congenital cataract (author's transl)]. In view of contradicting opinions regarding the chances by operations of unilateral congenital cataracts, we tested 97 children systematically since 1966. We especially tried to find out which functional meaning can be given to the operation and the following occlusion treatment. 64 children were operated, of these 22 in their 1. and 2. year of life, and an attempt of occlusion therapy followed. By 31 children test results were insufficient due mainly to the lack of cooperation of the parents who did not completely carry out the recommended therapy. In 2 patients the visual acuity improved clearly with central fixation. 6 children had a subjective, reliable orientation although their visual acuity lied under 0,2 and no central fixation was achieved. By the visual acuity and fixation test, they did not however differenciate from other children, who showed no improvement subjectively. The occlusion therapy was broken up by 15 children because of subjective discouragement and no signs of progression concerning the therapy. In retrospect serious operative complications within the observation time were not noted. Every type of cataract requires individual surgical techniques. Obviously, in such cases the measured visual acuity is not the appropriate criteria to judge the functional performance of the eye.


[Cataract extraction combined with trabeculotomy (author's transl)]. In this paper we report on a series of 56 eyes which underwent a combined cataract-trabeculotomy operation. After a follow-up of at least 6 months. 63% of the eyes had normal intraocular pressure while 34% of them required further medication to achieve the same. No serious complications were observed.


[Acupuncture in glaucoma (author's transl)]. Following the principles of classical Chinese acupuncture we treated 18 patients suffering from glaucoma chronicum simplex. We did not see any significant alterations of intraocular pressure whereas we attained improvement of recovery in some functional diseases such as blepharospasm or migraine. In our opinion therapeutic acupuncture works as a masked suggestive therapy. It is useless in organic diseases of the eye.


[Contusion of the eye--secondary glaucoma and other late consequences (author's transl)]. 24 patients were re-examined 19--20 years and another 37 patients 10--11 years after blunt injury to the eye. 24 eyes showed marked angle rears but there was not a single case of glaucoma. In case of initial a. c. hemorrhage these tears are significantly more ofter seen. 9 of the injured eyes had a reduction of visual acuity to 0.5 or less as a consequence of lens or central fundus changings.


[HLA antigens in patients with rhegmatogenous retinal detachment (author's transl)]. An analysis of HLA-antigens was carried out in 132 patients with rhegmatogenous retinal detachment. While emmetropic and hyperopic patients showed no deviation from the normal HLA distribution pattern, HLA-B 12 was found to be significantly increased (30,3% versus a control frequency of 21,8%) at the Pc less than 0,05 level in myopic patients. This deviation frequency was identical in patients with and without a positive family history and was not related to the degree of myopia.


[Amaurosis fugax and obliteration of the carotid artery (author's transl)]. Obliterative processes of the carotid bifurcation can be a starting point for cerebral and especially retinal microemboli. Early diagnosis is essential in protecting such patients from a definitive insult, or a reduction of sight which can go as far as permanent blindness, whereas the amaurosis fugax being the most common ocular symptom of the internal carotid insufficiency. Due to the fact ca. 65%--75% of the patients with ocular symptoms of a carotid insufficiency show forms of amaurosis fugax or photopical sensations, this symptom complex, especially in combination with temporary contralateral hemiparalysis, has to be evaluated as a classical symptom of carotid stenosis until the contrary can be angiographically proven. Only during the last few years has it become apparent that these microemboli originate from ulcerous or verrucous beds of the carotid bifurcation. The discovery of the above connections was only made possible through the improvements in carotid angiography technique.


[Fluorescence angiography in macular holes (author's transl)]. Studies were conducted on fluorescence angiography in lamellar macular holes. This methods allows to find some variations in ophthalmoscopically indentical cases what explains differences between their retinal functions. Using this method it is also possible to differentiate a tissue defect of the retina from other macular lesions.


[A comparison of measurements made with Goldmann's application tonometer and Draeger's hand applanation tonometer (author's transl)]. The hand held applanationstonometer Draeger gives reliable measurements of intraocular pressure, they correspond of those from Goldmann applanationstonometer. The eventual value deviations of i. o. pressure at the beginning of the tests are not caused by the instrument but mainly by the effect of repeated applanation tonometry.


[Experiences with Doppler-ultrasonography of the orbital vessels for ophthalmological vascular diagnosis (author's transl)]. With Doppler ultrasonography of the orbit the blood flow in the supratrochlear and supraorbital arteries can be determined transcutaneously. The technique yields reliable informations about the state of the carotid system. It is especially suitable for assessing carotid obstruction. Besides it has proved to be of particular diagnostic value in temporal arteritis. The authors describe and discuss the technique of orbital Doppler ultrasonography and present typical findings in carotid lesions and in temporal arteritis.


[Short-time storage of human corneas in medium NCTC 135 (author's transl)]. 20 human donor corneas were placed in a tissue culture medium (NCTC 135 with an additional content of 5% Actovegin resp. Solcoseryl) at +4 degrees C for 5 and 7 days. After that the temperature reversal effect was measured and the corneal endothelial cells were stained. The living cells were counted every 24 hours until no more cells could be seen. It could be shown, that compared with the MK-Medium 24% more living cells could be counted after 5 and 7 days storage in the medium. Possible causes of this improvement, practical consequences with including antibiotic prophylaxis are discussed.


[Systemic diseases in patients with cataract-extraction (author's transl)]. 214 patients who underwent cataract-extraction in 1973 were examined for systemic diseases. The average age of patients with (70%) and without (30%) general diseases was 67 years. The frequency of cardio-vascular and respiratory diseases corresponded to that observed in the general population of the same age. In contrast, the rate of diabetes mellitus was four times higher than to be expected statistically. The importance of an adequate clinical management of diabetic cataract patients is discussed.


[On eye changes associated with the pigmented spots syndrome (Peutz-Jeghers) (author's transl)]. After a survey of cases of the pigmentpolyposis (Peutz-Jeghers) in the literature reported, a woman with an abortive form of this syndrome (pigmentanomaly ) and a bilateral embryotoxon posterius (Axenfeld) is described. Both signs are heritable in the autosomal-dominant manner. The association of pigmentpolyposis and embryotoxon is not yet observed. Possibly there is present a new-mutation. The examination of the family detected no other special cases. For the future on had in cases of pigmentpolyposis possible ocular changes more in view than till now.


[On the treatment of arteriosclerotic retinopathy with Cosaldon A+E (author's transl)]. Cosaldon A+E was applied in 61 patients, most of whom presented severe vascular degenerative retinochoroidal circulatory disorders and chronic glaucoma. The treatment, mostly consisting of 3--2 x 1 tablet per day, was well tolerated and resulted in marked (43 patients) and moderate (8 patients) improvement of visual function. In ten patients the symptoms remained unchanged. Particularly the improvement found in 4 patients presenting chronic glaucoma "without pressure" are worth mentioning. Besides, the symptomatology of chronic cerebrovascular insufficiency presented by most of the patients was positively influenced. Cosaldon A+E above all renders more promising the treatment of vascular processes in the eye-ground, such as the chorioretinopathy, which, in view of the unfavourable prognosis of the disease, is deemed a remarkable progress. Likewise the product seems to exert a beneficial effect in patients with chronic glaucoma.


[Some special indications for wearing contact lenses (author's transl)]. The typical distinguishing features of special cases which require contact lenses for satisfactory vision are described. Hence in the first case with anisometria associated with irregular astigmatism of one eye, to which a toric soft contact lens was adapted. In the second case a visual acuity of only 0,6 monocular was attained with the best spectacle lens, however with contact lense the visual acuity was 1.25. Here a verdict from a social court is mentioned, which obliged the sickness insurance to take over the costs for such a case. In the third case the adaptation of contact lenses was undertaken after radical bilateral keratoplasty because of parenchymatous keratitis, and an improvement in visual acuity of at least 400% resulted.


[Experience with the new photocoagulator (Zeiss) (author's transl)]. The new Zeiss Xenon-photocoagulator has considerable advantages. The possibility of converging the light beam allows coagulating even prominent areas (folds) in lensless eyes without difficulty. From our experience Xenon coagulation with individually adapted coagulation offers advantages over argon-laser coagulation with relatively short coagulation times.


[Comparative studies with scanning electron microscope on the quality of corneal disk incision using various corneal trephine (author's transl)]. The cut surface of corneal stroma from rabbits was studied with a scanning-electron microscope and compared after using a manual trephine, a motor-driven rotor trephine and a rotor trephine with mechanical guidance. It became evident that the cut surface obtained with the motor-driven trephine is clearly smoother than that obtained with manual trephine. A further improvement in the quality of the cut is evident with a mechanically guided trephine.


[Obligation to tolerance and reasonability of cataract extraction (author's transl)]. The reasonability of cataract extractions is mentioned with exposition of the interests of the insuring bodies and of the patient. We discuss individually the terms "medical treatment", "obligation to tolerance" and "reasonability". The surgical method and the general physical assessment of the patient earn special consideration for a "reasonable" cataract extraction. We also discuss the special situation of the surgeon.


[Allergy diagnosis in patients with bronchial asthma (bronchial provocation test, skin test and RAST) (author's transl)]. 87 patients with bronchial asthma underwent skin test, RAST and measurment of airway resistance before and after inhalation of control solution as well as at least 10 times after each of one to four bronchial provocations (making up a total of 171 tests) with extracts of house dust, house dust mite, animal dander, mould spores and pollen in increasing concentrations. An actual clinical significance of the skin test reactions was found in 60% of all cases and of the RAST results in 66% of all cases. The overall agreement between skin test results and RAST results was 61%. The correlations between the different tests depended on the degree of hypersensitivity, on the tested allergen and on whether the results of skin test and RAST, respectively, were positive or negative. There existed a good correlation between the results of all three test methods and case history only for pollen allergens and animal dander. Noticeably often negative RAST results with house dust and mould spores, as well as positive skin tests with house dust mite and mould spores could not be confirmed by the provocation test. Important indications for a bronchial provocation test in asthmatics are doubtful case history, doubtful skin test or RAST results with the problem-allergens house dust, house dust mite and mould spores; the bronchial provocation test is especially commendable when drastic or cumbersome therapeutic measures (immunotherapy, change of home, change of job) are to follow or if late asthmatic reactions are expected.


Haemodynamic effects of the beta-receptor blocking agents metoprolol and propranolol in the anesthetized dog. The haemodynamic effects produced by intravenous infusions of the beta-blocking agents metoprolol and propranolol in doses of 0.3 and 1 mg/kg/10 min were compared in anaesthetized dogs. When administered in a dose of 0.3 mg/kg/10 min, metoprolol caused a longer-lasting increase in pulmonary-arterial pressure and total pulmonary resistance, a greater increase in pulmonary capillary pressure and a more marked decrease in O2 partial pressure in the arterial blood than propranolol. These differences are probably due to differences in the pharmacokinetics of the two drugs. The effects of the two beta-blockers in a dose of 1 mg/kg/10 min were similar. At neither of the dose-levels tested were the changes induced by the compounds in the various parameters studied clearly dose-related.


Application of bradykinin radioimmunoassay for the measurement of urinary kallikrein activity rats. Bradykinin radioimmunoassay was applied for the measurement of urinary kallikrein activity in rats. Antisera against bradykinin were raised in rabbits by injecting synthetic bradykinin coupled to human serum albumin via a difluorodinitrobenzene reaction. For radioimmunoassay a high titre antibody was used at a final dilution of 1:65000 to bind approximately 8,000 cpm of [125I]-tyrosine8-bradykinin. Standard curves were plotted from synthetic bradykinin samples (1--1000 pg). Kinins were generated by incubating partially purified kininogen with rat urine in the presence of kininase inhibitors. Bradykinin antiserum showed crossreaction with kallidin, met-lys-bradykinin and dog-kininogen. To eliminate interference of the kininogen with kinin radioimmunoassay, alcohol precipitation of the substrate was performed after incubation. Concentration of urinary kallikrein in rats showed no significant difference between day and night 12-hours-colllecting period. Total kallikrein excretion at night, however, was about twofold higher, correlating to a twofold higher urine volume during the night.


Effect of sodium nitroprusside alone and in combination with sodium thiosulfate on the acid-base balance, and on thiocyanate and iron plasma levels in the rabbit. An infusion of 7.5 mg/kg.h sodium nitroprusside (SNP) produced a fatal cyanide intoxication in conscious rabbits (n=6) after 60.8 +/- 6.7 min (chi +/- S.E.). When, however, the cyanide antidote sodium thiosulfate was infused simultaneously at a rate of 31.25 or 62.5 mg/kg.h, i.e. a molar SNP/thiosulfate ratio of 1:5 or 1:10 respectively, this high dose of SNP was well tolerated. In both concentrations, thiosulfate abolished the development of the severe metabolic acidosis that results from the infusion of toxic doses of SNP alone. In the presence of thiosulfate, the plasma level of thiocyanate rose linearly with the infusion time indicating a rapid detoxification of cyanide released in vivo from SNP, whereas at the end of the infusion of SNP alone no increase in plasma thiocyanate could be measured. No clear advantage of the higher thiosulfate dosage over the lower one could be established. The iron plasma level only rose during the first hour of SNP plus thiosulfate infusions reaching the iron binding capacity of plasma, and then remained stable throughout the experiment. This indicates that the iron plasma level is an unsuitable parameter for the control of SNP therapy. We suggest the simultaneous administration of SNP and thiosulfate at a molar ratio of 1:5 to make SNP a safer drug.


Reversal of renal hypertension: effects on renin, salt and water balance. The effect of removal of one renal artery stenosis on renal sodium and fluid excretion and on the activity of the renin-angiotensin system (RAS) has been investigated in three types of renal hypertension of rats. Blood pressure fell in all experimental models after declamping, independently of changes in urinary sodium and water excretion or plasma angiotensin II (ANG II). Plasma concentrations of ANG II did not rise in response to salt and fluid loss induced by declamping when the contralateral kidney had been removed or when it was depleted from renin. A high renin content of the declamped kidney prevented major salt and fluid loss, whereas renin depletion of this kidney was accompanied by an exaggerated natriuresis and diuresis. Besides this tubular modulation of renal salt and water handling by the local RAS, glomerular filtration rate could be reduced by a stimulated activity of this system in plasma, indicated by a close relationship between serum urea and plasma ANG II levels.


In vivo enzyme activity of purified human brain renin. Cerebrospinal fluid (CSF) of rats contains high angiotensinogen concentrations. When 3500-fold purified renin from human brain was injected into the brain ventricles of rats, angiotensin I concentrations increased from undetectable levels to 147.9 +/- 18.8 fMol per ml CSF. In parallel, mean arterial blood pressure increased from 93 +/- 2.4 mm Hg to 107 +/- 3.7 mm Hg. The increase in blood pressure could be abolished by intraventricular administration of saralasin, a blocker of angiotensin II receptors. Intraventricular injection of cathepsin D had no effect on arterial blood pressure and the agiotensin I concentration in CSF remained below detection limits of the radioimmunoassay. We conclude that brain renin acts on endogenous brain angiotensinogen under physioloical in vivo conditions to form angiotensin I. The latter is converted to angiotensin II and leads to biological effects, i.e. increase of blood pressure.


Increased blood pressure responses to central angiotensin II in spontaneously hypertensive rats. The blood pressure responses following infusions of angiotensin II (ANG II) into the brain ventricles (i.v.t.) have been tested in spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) rats. The mean arterial blood pressure increases were significantly higher in SH rats than in WK rats. Propranolol treatment reduced blood pressure increases to i.v.t. ANG II in WK, but not in SH rats. The higher sensitivity to i.v.t. ANG II in SH rats supports a role of central ANG II in the maintenance of high blood pressure in SH rats.


The influence of vinblastine and colchicine on renin secretion in vivo and in vitro. The effect of the microtubule inhibitors colchicine and vinblastine on renin release in vivo and in vitro was studied. Injection of 0.5 mg/100 g i.v. of colchicine or vinblastine to furosemide treated rats on a low salt diet resulted in a decrease of plasma renin as well as plasma angiotensinogen concentration during a 5 h observation period. Renin release from rat kidney slices was diminished by vinblastine (5 x 10(-5) M), when basal or stimulated (by isobutylmethylxanthine and isoproterenol) renin release was measured. Colchicine at 5 x 10(-5) M had no effect under these conditions. Renin release from the isolated perfused rat kidney was increased 2--3 fold by vinblastine (10(-5) M) or colchicine (10(-4) M). The maximal response of renin release to isoproterenol (10(-7) M) was not changed when vinblastine (10(-5) M) or colchicine (10(-4) M) were present in the perfusion medium. The contrasting results cast considerable doubts on the suitability of microtubule inhibitors in studies on renin secretion.


Neurohypophyseal vasopressor principle: vasopressor hormone as well as antidiuretic hormone? Studies on the vasopressor role of the antidiuretic hormone arginine-vasopressin (AVP) in DOC hypertension, in two-kidney Goldblatt hypertension, and in spontaneous hypertension of rats, and during acute blood pressure elevation after intracerebroventricular injection of angiotensin II and in glycerol-induced acute renal failure of rats are reviewed. For the measurement of plasma AVP a radioimmunoassay has been developed. For this assay, a series of criteria has been met which allows the conclusion that, in plasma of rats, the antibody measures AVP only. For the blockade of vasopressor effects of AVP a specific antiserum has been used. On the basis of a series of control studies it has been concluded, but not proven that the antiserum lowers blood pressure exclusively by blockade of AVP. It could be shown that in the various animal models of hypertension and of acute blood pressure elevation AVP exerts systemic vasoconstriction when its plasma concentrations are elevated. In those models where the renin-angiotensin system played no role in blood pressure control, the height of blood pressure was closely related to the plasma AVP concentrations. When this relationship was compared with that obtained after the i.v. infusion or injection of AVP, a marked shift to the left became apparent. Hence, sensitization to the vasopressor effect of AVP had occurred, the factor of sensitization amounting to more than 1,000. It is concluded that AVP is not only an antidiuretic hormone but also a vasopressor hormone, and that any systemic vasopressor effect of AVP requires a mechanism of sensitization.


Vasoactive peptides in experimental renal hypertension. 1. Blood pressure is controlled by both integrated neurogenic and humoral vasoactive mechanisms. 2. Both vasopressor (angiotensin and vasopressin) and vasodepressor (bradykinin) hormonal peptides have been identified. 3. In acute experimental renal hypertension in the rat plasma renin, angiotensin and vasopressin have all been shown to be elevated. 4. Associated with this increase in vasopressor hormonal peptides, urinary kallikrein excretion has been demonstrated to be reduced during the development of renal hypertension. 5. The level of blood pressure achieved in experimental renal hypertension is probably a summation of these vasoactive peptides as well as other factors.