A method for quantitating intracardiac bidirectional shunt and estimating its blood flow is presented. Three curves, defined as "right-to-left shunt curve", "normal pathway curve", and "left-to-right shunt curve" were separately drawn from the original downstream dye-dilution curve, and their areas A", A, A' respectively, were calculated in the conventional manner. A'/A showed left-to-right shunt ratio (Q_L-R%) even in the presence of right-to-left shunt. However, right-to-left shunt ratio (Q_R-L%) was given by (1-A'/A)/(A/A"+1-A'/A), and equalled A"/(A + A") only when left-to-right shunt was absent (A'= O). A"/(A + A") should become increasingly higher than Q_R-L% with rise in Q_L-R% (= A'/A). The relationship between A"/(A + A") and Q_R-L% for various A"/A isopleths is shown by figure. A good agreement (r = 0.848, p < 0.001) was found between Q_L-R% values by the present method and those calculated by the oxygen method. In contrast, Q_R-L% values by the present method were consistently lower than those by the oxygen method; the difference was exaggerated especially in cases with history of cardiac failure, and these cases tended to show lower systemic flow. The average difference in Q_R-L% between the two methods, found in cases free from failure; was 7 per cent. This was thought to be ascribed to intrapulmonary physiological shunt.

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Six hundred and twenty-two autopsies of patients with malignant neoplasm were used for this study in order to analyze the incidence of cardiac involvement in relation to the sites of the primary tumor, the anatomical distribution within the heart, and the ECG findings in tumor patients with and without cardiac involvement. Our findings were then discussed in the light of previous reports. 1) The overall incidence of cardiac involvement by malignant tumor was 12.7% (79 outof 622 cases), and the average incidences in carcinomas, sarcomas and the other groups were 1 3.0%, 7.7%, and 17.0%, respectively. Among various carcinomas, breast and pulmonary cancer showed a very high incidence of cardiac involvement, while intestinal and gastric cancer were found to metastasise infrequently to the heart. 2) The incidence of epicardial involvement was very high (65.8%) and that of involvement of the pericardium, myocardium and endocardium was 38.0%, 29. 1% and 19.0%, respectively. 3) No significant difference was observed in the ECG findings recorded between 3 to 6 months, or over 6 months before death between the groups with and without cardiac involvement. 4) A significant difference in the incidence of myocardial damage pattern, arrhythmia and/or intraventricular conduction disturbance (such as ST-T depression, sinus tachycardia or incomplete right bundle branch block) was observed in the ECG recorded within 3 months before death when comparing with the groups with and without cardiac involvement. 5) The cases with metastases to the myocardium were always associated with the pattern of myocardial damage on the ECG.

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1) In rats treated with DOCA plus high salt or with high salt alone, hypertensive rats with renal vascular lesions showed an incomplete suppression of KRA. Cathepsin activity of rat kidney was higher under high salt loading than in the control. Beta-glucuronidase activity was greatest in rats with renal vascular lesions and smallest in rats fed on normal chow. RNase and DNase activities were greater in rats with renal vascular lesions than in rats without renal vascular lesions under high salt loading. 2) In rats of both sexes SHR showed greater KRA and cathepsin activities than WK rat under high salt loading. In female rats DNase, RNase and β-GPase activities were greater in SHR than in WK rat under high salt loading. 3). KRA was higher in SHRSP aged 10 months than in SHRSR, though KRA of SHR was smaller than KRA of WK rat. Cathepsin activity was greater in SHRSP than in SHRSR. DNase and β-NAGA activities were greater in SHR than in WK rat . 4) In 7 weeks of age SHRSR showed more PRC than SHRSP. At the age of 10 months SHRSP showed higher PRC than WK rat. The roles of renin and lysosomal enzymes in hypertensive renal vascular lesions were discussed to some extent. (This research is sponsored by the Science and Technology Agency of Japanese Government.)

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The effects of alterations in the extracellular Ca concentration and of lanthanum, verapamil and manganese were examined in the following four modes of contraction in vascular smooth muscle. Observation was also made on the relative effectiveness of Sr and Ba as substitutes for Ca in these contractions and in responses of relaxation by isoproterenol and papaverine. (1) .Spontaneous rhythmic contraction of rat portal vein was eliminated in Ca-O PSS and by lanthanum, verapamil and manganese. Sr could replace Ca with approximately the same effectiveness in generating phasic contraction but Ba produced only tonic contraction but not phasic contraction. (2) Spontaneous tonic contraction of resistance vessel from rat skeletal muscle disappeared when external Ca was removed and the Ca permeability blocking agents were added to perfusate. Sr and Ba could replace Ca. The order of effectiveness to maintain myogenic tone was Ba ≥ Ca > Sr. (3) Potassium-induced contraction of dog jugular vein was lost in Ca-O PSS and by lanthanum and verapamil. Sr and Ba were as effective as Ca in the substitution. (4) Norepinephrine-induced contraction of dog jugular vein remained partly in Ca-O PSS and after lanthanum and verapamil. However the residual response was greatly deteriorated. Sr and Ba was equally less effective than Ca. The importance of extracellular Ca, plasma membrane Ca and Ca entry into the cell in these modes of contraction was demonstrated. The diverse effectiveness of Sr and Ba in substitution of Ca may suggest different contractile mechanisms among the four modes of contraction. (5) Relaxation of isoproterenol was remarkably reduced or hardly observed in Ba or Sr PSS. A small amount of Ca restored relaxation in Ba and Sr solutions. (6) Relaxation by papaverine was demonstrated constantly and in the similar effectiveness among Ca, Ba and Sr solutions. This is an evidence for different mechanisms of relaxation between the two drugs. It is suggested that Ca is more effective in adrenergic drug and receptor interaction, whether contraction or relaxation than Ba and Sr.

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Cardiovascular responses to cold stress were investigated in hypertensive patients. There were few differences in the changes under cold stress of the serum catecholamine concentration between the juvenile group and middle-aged group. In the juvenile group, a remarkable increase in TPR was observed under cold stress, suggesting that the vascular reactivity is increased and at the same time the cardiac response to inotropic action was increased under cold stress. On the contrary, in the middle-aged group, there was less increase in TPR under cold stress and no increase in' inotropic action was observed. From such results, hyperreactivity to stress in the cardiovascular system is thought to be an important factor in the pathogenesis of essential hypertension. Such cardiovascular responses are seen more easily in juvenile hypertension or initial stage of essential hypertension. In the hypertensive patients after middle-age, organic changes will develop by the repeated pressure load to the cardiovascular sytem caused by various stimulations and the reactivity of cardiovascular system to stress becomes less manifest.

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The concentration of plasma catecholamines (CA), serum dopamine beta-hydoxylase (DBH) activity and plasma renin activity (PRA) were simultaneously measured in 55 patients with essential hypertension (EH). Further, the enzyme activities of CA biosynthesis in human vas deferens excised at elective vasectomy were related with the blood pressure, plasma CA, serum DBH of 57 men at the time of vasectomy. Total plasma CA and norepinephrine (NE) were increased in 28 and 35% of patients with benign EH, respectively. Total plasma CA were also increased in 45% of men with elevated blood pressure prior to vasectomy. Total plasma CA were correlated with diastolic blood pressure in EH (p < 0.01). Further, in men with normal and raised blood pressure prior to vasectomy, there was a significant correlation of total plasma CA with systolic and diastolic blood pressure (p < 0.01). Total plasma CA were correlated with PRA in patients with EH (r = 0.497, p < 0.001). Capacity for NE biosynthesis, vas deferens tyrosine hydroxylase (TYH) activity and dopa decarboxylase (DDC) activity were increased in men with raised blood pressure. There was a direct correlation of total plasma CA with the activities of TYH and DDC (r = 0.46, and 0.54, p < 0.005). Increased sympathetic nerve tonicity associated with increased neuro-transmitter biosynthesis may be an important factor responsible for blood pressure elevation in men prior to vasectomy and in others with EH. The some patients with EH may have a renin-catecholamine relationship and both pressor systems may be linked to be a pathogenic factor for the elevation of blood pressure.

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CI, TPRI, PV, ECFV, Nae, PRA and a pressor response to NA and AT was measured before and after 1) sodium restriction and 2) spontaneous blood pressure fall (spontaneous fall) in the patients with essential hypertension and the following results were obtained. 1) CI did not change during sodium restriction and increased after spontaneous fall. TPRI was reduced and the degree of this reduction was positively correlated with that of blood pressure reduction under these two conditions. 2) Sodium restriction caused the decrease of PV, ECFV and Nae and the increase of PRA. The degree of the reduction of PV and Nae was positively correlated with that of blood pressure fall. After spontaneous fall, PV, ECFV and Nae was increased and PRA did not change significantly. 3) A pressor response to NA and AT was depressed after one week of sodium restriction, and after 4 weeks the former returned to the basal response, while the latter was still reduced. NA response was correlated positively with basal Nae, ECFV and interstitielle fluid volume and negatively with basal PRA. AT response was negatively correlated with PRA before and during sodium restriction. No correlation was observed, however, between the degree of reduction of blood pressure and that of the change in pressor response to NA or AT. After spontaneous fall, the response to NA was not reduced but increased. These results suggested that, although the fall in blood pressure under these experimental conditions was mediated by the reduction of TPRI, the changes in pressor response to NA and AT did not affect primarily the reduction of blood pressure.

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The selectively-bred substrains of spontaneously hypertensive rats with a greater vulnerability to vascular lesions rapidly developed arterial fat deposition within 1 or 2 weeks as well as a greater hypercholesterolemics response when fed on high fat cholesterol diet including 20% of suet, 5% of cholesterol and 2% of cholic acid. The ring-like arterial fat deposition at the branches of superior mesenteric arteries and cerebrobasal arteries, which was found to be good indices for the deposition of intrarenal or coronary arteries, was not observed in normotensive rats fed on high fat cholesterol diet for 3 months, greatly delayed in SHR under antihypertensive treatment and accelerated by 1% salt loading in drinking water. The horseradish peroxidase infused intravenously 1 to 4 hours before sacrifice leaked in ring-like forms which corresponded to the fat deposit in mesenteric arteries. The incorporation of ³H-proline infused 4 hours before sacrifice was enhanced in the mesenteric arteries with the fat deposition. These results clearly indicated that hypertension was a great contributory factor to rapid arterial fat deposition, which was caused by an increased vascular permeability and enhanced the arterial collagen formation, the initiation process of arterio- or atherosclerosis.

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The cerebrovascular permeability quantitatively determined by the retention of ¹³¹I-human albumin in the perfused brains was increased in SHR, especially in stroke-prone SHR compared with normotensive Wistar-Kyoto, and confirmed the macroscopical or microscopical findings on the leakage into the brain of trypan blue or peroxidase injected intravenously 2 to 3 hours before sacrifice. The localization of increased vascular permeability in SHR cor-responded to the predilection sites of cerebral hemorrhage or softening, which developed likely following the increased cerebrovascular permeability.

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The offspring of male stroke-prone SHR, 80 in total, were devided into treated and nontreated groups at the age of 30 to 45 days. The former groups were treated with a-methyl dopa (2g/l in the drinking water), or L-dopa (2g/l) with or without peripheral decarboxylase inhibitor (MK-486, 1-3g/l) or apresoline (0.08g/l) thereafter till they died a natural death during 1 and a half year observation period. So far as hypertension was controlled under about 210mmHg, no stroke was observed, while nontreated group developed cerebrovascular lesions spontaneously in about 80 per cent. This study experimentally confirmed the importance of blood pressure control for the prevention of stroke.

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Many authors have reported the changes of myocardial lactate metabolism during angina or coronary insufficiency induced by exercise or atrial pacing. However, a precise correlation of myocardial carbohydrate metabolism with electrocardiographic changes during exercise has not been studied for various circulatory diseases. The purpose of this paper is to clearify the aspect of myocardial carbohydrate metabolism and its role for the myocardial energy source under the condition in which the exercise load is so intensive that the appearance of ischemic ECG changes can detect the coronary insufficiency. Methods and Subjects: The arterial blood taken from brachial artery and coronary sinus sampled by coronary sinus catheter was analised. The sampling was carried out three times, immediately after the insertion of coronary sinus catheter, after keeping rest before exercise and ten minutes after starting exercise. Blood glucose was determined by glucose oxidase method, lactate by hydroxybiphenyl method according to Barker and Summerson and pyruvate by dinitrophenylhydrazine method according to Friedemann and Haugen. Coronary blood flow was measured by the nitrous oxide method. Exercise was performed in the supine position at a level of fifty watts for fifteen minutes with bicycle ergometer. Thirty six patients with circulatory diseaes who were fasting for six to eighteen hours were studied, consisting of 5 with neurocirculatory asthenia (NCA), 8 with hypertension without coronary insufficiency (HT), 7 with hypertensive coronary failure (HTC), 7 with normotensive coronary heart disease (CHD) and 9 with the other heart diseases (HD) such as valvular disease etc. All subjects were also classified into 3 groups according to the electrocardiographic changes before and after the exercise test, namely, 17 cases of the negative test group before and after Master's double two-step test or bicycle ergometry, 16 cases of the positive test group whose ECG showed ischemic changes after the exercise tests or also before exercise and 3 cases of the improved group whose ischemic ECG changes were partly normalized after exercise.

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