In 50 patients with acute myocardial infarction (16 patients with previous infarction and 34 patients without), total creatine phosphokinase (CPK) released which represents infarct size was calculated from the serial change of serum CPK activity by the method of Sobel improved by Norris, and related it to the presence or absence of heart failure, the ejection fraction and one-year-mortality. If the patients with previous myocardial infarction were excluded, mean total CPK released in 10 patients with heart failure (1428 ± 200.4 IU/ml in Group II) was significantly larger (P<0.01) than that in 24 patients without heart failure (735.3 ± 83.6 IU/ml in Group I). However, in patients with previous myocardial infarction there was no significant difference in infarct size between these two groups (Groups I and II) indicating that the complication of heart failure does not directly relate to the size of the recent infarction but in large extent to the presence of prior infarction. The ejection fraction was obtained in 15 patients who had left ventriculography. Both of two patients with prior myocardial infarction in these 15 patients showed smaller ejection fraction than the predicted values myocardial infarction could contribute to impaired cardiac function as well as the recently occured infarction. One-year-mortality in Group II (37.5%) was higher than that of Group I (7.4%). In four patients with prior infarction who died within one year after the onset, mean total CPK released (275.3 IU/ml) was significantly smaller than that in three patients without prior infarction (899.0 IU/ml). These results strongly suggest that the patients with previous myocardial infarction are often complicated with heart failure and have poor prognosis even with comparatively small infarction and also demonstrate the substantially large contribution of the reduced contractility resulting from the previous myocardial infarction to the impaired cardiac function.

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In surface-induced deep hypothermia, metabolic acidosis resulting from lactacidemia was observed. In the aspect of myocardial metabolism, the rate of reduction in coronary A-V difference ratio of lactate, pyruvate and NEFA was less than that of coronary flow and myocardial oxygen consumption in the hypothermic heart. Namely, it seems that lactate, pyruvate and NEFA play an important role as energy fuel in the hypothermic heart. On the other hand, myocardial metabolism of glucose was reduced in the hypothermic heart. Moreover, it seems that exogenous corticosteroid and ATP do not influence on the myocardial metabolism of carbohydrate and lipid in the hypothermic heart.

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The cardiovascular effects of isometric handgrip exercise were determined with a nonivasive method in the patient with artificial pacemaker. The arterial blood pressure was measured with mercury manometer as well as cardiac output by the dye dilution method with Indocyanin green before and after handgrip exercise. Isometric handgrip exercise produced a significant increase in the left ventricular ejection time index/the isometric contraction time, the arterial blood pressure and cardiac output and a significant decrease in the preejection time and the isometric contraction time. Cardiac output was increased more remarkably in the negative Master two step test group than in the positive Master two step test group. There was found a significant positive relationship between the increase in cardiac output and P wave rate upon handgrip exercise.

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Urinary excretion of kinin, of kallikrein, of prostaglandin (PG) E and A, of main urinary metabolite (MUM) of PGF₂α and plasma PGE concentration were measured in healthy subjects and in hypertensive patients. The kallikrein excretion rates were 111 ± 11.0 (SE) KU/day in 21 normal subjects, 75 ± 10 KU/day in 23 patients with essential hypertensives and 175 ± 23 KU/day in 9 patients with primary aldosteronism. The kallikrein output in urine was decreased in essential hypertension, while increased in primary aldosteronism. The excretion rates of urinary kinin were increased in primary aldosteronism. The excretion rates of urinary kinin were 44.8 ± 5.9 μg/day in 24 normal subjects and 21.7 ± 4.7 μg/day in 19 patients with essential hypertension. The urinary kinin excretion was also decreased in essential hypertension. The PGE and A excretion rates were 482 ± 5.5 ng/day in 17 normal subjects and 321 ±44 ng/day in 26 patients with essential hypertension. The urinary output of PGE and A was decreased in essential hypertension. Regarding the output of PGF₂α-MUM or plasma PGE concentration, there was no significant difference between normal subjects and essential hypertension. Influences of furosemide on urinary kallikrein and PGE were examined. Enhancement of urinary excretion of kallikrein and PGE were found in normal subjects and in essential hypertension after the administration of furosemide. The percent increases of urinary kallikrein output were 489% in normal subjects and 312% in essential hypertension, and urinary PGE output were 518% in the former and 143% in the latter. In essential hypertension the increase was smaller than in healthy subjects. The present experiment proved a decrease in synthesis of renal kallikrein, kinin, and PGE in essential hypertension, suggesting that suppression of renal depressor system is one of the etiological factors in essential hypertension.

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Effects of angiotensin III and angiotensin III analogue upon adrenal steroidogenesis and blood pressure were studied in rats, rabbits and a man. Pressor effect of angiotensin III was about one fifth of that of angiotensin II in all the species. Degradation rate of pressor effect of angiotensin III in plasma was more rapid than that of angiotensin II. Different from the effects of angiotensin III upon blood pressure, its effect upon aldosterone was similar to that of angiotensin II. The effect of angiotensin III upon other adrenal steroids, such as DOC and cortisol, however, seemed to be slightly less than that of angiotensin II. Angiotensin III produced an additive effect to that of ACTH, but it didn't produce and additive effect to that of angiotensin II. Angiotensin III analogue, itself, stimulated adrenal steroidogenesis, but it inhibited the effects of angiotensin III and angiotensin II upon aldosterone. Effects of ACTH upon plasma DOC and cortisol were not inhibited by angiotensin III analogue, but the effect of ACTH upon aldosterone was blunted slightly.

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Plasma dopamine-β-hydroxylase (DBH) activity was examined in nine healthy young adults. DBH activity at rest had a wide range, near 0 to 44 I.U./L. When sodium depletion was performed by dietary sodium restriction and diuretic, the activity was significantly increased. With dietary sodium loading, it was decreased. The change in DBH activity was significantly correlated with that in hematocrit. When subjects were erected, the enzyme activity was elevated in situations regardless of sodium balance. Blood pressure and pulse rate were changed by manipulation of sodium balance and postural change. However, the change in DBH activity did not correlate with them. Plasma renin activity (PRA) was determined concomitantly in the same plasma with DBH. The change in PRA had a direct correlation with that in DBH activity. Furthermore, the change in mean arterial presure induced by infusion of angiotensin II analogue seemed to correlate with DBH activity change by sodium depletion. When the values of DBH activity in each individual were compared throughout the study, it was observed that the biggest variance in the activity of each individual was significantly correlated with the basal activity. In longitudinal study of individuals, plasma DBH activity could be a usuful index for estimation of sympathetic activity.

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Using a continuous systolic monitor, effects of oral administration of three α-adrenergic blockers, i.e. phenoxybenzamine, phentolamine and a new quinazoline compound (2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6, 7-dimenthoxy-quinazoline; E-643), on blood pressure and heart rate in normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). 1) An oral dose of 1 mg/kg phenoxybenzamine or E-643 almost completely reversed pressor response to adrenaline (2 μg/kg i.v.). Phentolamine was 3 to 5 times less effective than phenoxybenzamine and E-643. These α-blockers reduced pressor response to adrenaline (2 μg/kg i.v.) merely to one half at an oral dose of 100 mg/kg. 2) All these α-blockers did not other hand, they reduced blood pressure of SHR without marked increase in heart rate. Although the α-blocking and cardiac stimulating effects of phenoxybenzamine lasted more than several days, its hypotensive effect in SHR disappeared within 24 hours. 3) An oral dose of 30 mg/kg propranolol did not reduce blood pressure in both NWR and SHR but slightly decreased heart rate. The combined treatment of these α-blockers with propranolol completely abolished the cardiac stimulating effect of the α-blockers and resulted in a difinite reduction in blood pressure of NWR and potentiated the hypotensive effect of α-blockers in SHR.

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The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1, 278 SHRSP. The precise supply to the main cerebral arteries was determined by trypan blue injections and microangiography. The three major territories were the anteromedial cortex, the occipital cortex, and the basal ganglia. A common angioarchitectural characteristic of these areas was the blood supply through"recurrent branchin"from the main stream. In the basal ganglia, where there is a preponderance of lesions, the arteries responsible for these lesions belonged to the lateral group of lenticulostriate arteries. The primary prestroke arterial lesions were further studied microangiographically in SHRSP killed at the time the initial symptoms of stroke were detected. These points were located at the"boundary zone"of the main cerebral arteries. Such findings indicated the importance of these two angioarchitectural minor loci as the basis for functional or organic circulatory disturbances that might cause stroke. Since these local factors for fufactors for stroke are common in the cortex and basal ganglia of rats and basal ganglia of humans, these SHRSP are regarded as good pathogenetic models for studies on stroke in humans. After simultaneous bilateral carotid ligation, accelerated induction of cerebrovascular lesons in young SHRSP and stroke-resistant SHR (SHRSR) showed predilection sites of stroke approximately consistent with those in SHRSP after natural death. (and rather consistent with those in humans). Such findings comfirmed that these lesions developed at the"minor loci"of cerebral circulation fed by"recurrent branches"from the main cerebral arteries. Regional cerebral blood flow (rCBF) was repeatedly measured by the hydrogen clearance method in both frontal and temporal cortices of SHRSP at the age of 50 days and thereafter. When SHRSP developed severe hypertension over 200 mmHg at the age of 60 days, rCBF in both frontal and temporal cortices began to decrease abruptly, especially in the frontal region of the cortex-one of the three pretension and at the hypertensive steady state, the frontal region constantly showed lower rCBF values than the temporal region. In contrast, such a reduction in rCBF was not noted in either SHRSR which developed moderate hypertension under 200 mmHg, or in Wistar-Kyoto rats (WK) with normal blood pressure under 150 mmHg.

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