The dilatation of the aortic valve portion was evaluated by angiography in 70 patients with aortitis syndrome (Takayasu's arteritis)
The diameter at aortic valve commissure was 20±2.8mm/M² (NS, vs control) in 46 patients without aortic insufficiency (AI), 23±2.0 (p<0.01, vs without AI) in 11 patints with AI (I or II in grade), 27±2.0 (p<0.01, vs I or II in grade) in 13 patients with AI (III or IV in grade). The diameter was 20±2.0 in 13 normal control cases and 20±4.0 in 6 patients with rheumatic AI
The diameters at the levels of aortic valve annulus, sinus of Valsalva and ascending aorta increased also significantly in the patients with AI secondary to aortitis syndrome
The diameter at aortic valve commissure in 24 patients with AI was correlated (r=-0.48, p<0.05) to the diastolic blood pressure.
Any diameter at the aortic valve portion was not different significantly by the complication of systolic hypertension (≥180mmHg) in both groups of cases with and without AI
These results indicated that the dilatation of the aortic valve portion was observed in the patient with AI secondary to aortitis syndrome and might be the primary and common cause of AI in all grades, and that the dilatation might not be accelerated by the associated hypertension

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The amplitude of the pulmonic component of the second sound in aortic stenosis was studied in 49 patients with this lesion. As controls, 50 normal subjects were also studied. Both groups were investigated by phonocardiography, apex cardiography and arterial tracings. Nineteen patients with aortic stenosis and four subjects without it were also studied by cardiac catheterization and angiography. The amplitudes of the two components of the second sound were compared, and the ratio of each with the amplitude of the first sound was determined. The ratios of both the aortic and the pulmonic component to that of the first sound were decreased in aortic stenosis, and the decrease of the pulmonic component was comparable to that of the aortic component. These findings could be related to prolongation of the isovolumic relaxation period of both ventricles cused by an influence of the left ventricle on the right, most likely due to functional changes of the interventricular septum

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Pulsed Doppler echocardiography (PDE) was performed on 41 patients with aortic insufficiency (AI), isolated or associated with other cardiac diseases, using an ATL 500A pulsed Doppler system. The diagnosis was confirmed by angiocardiography in 25 cases. The purpose of the present study was to analyze the disturbed flow due to AI, to investigate the sensitivity of PDE to this lesion, and to compare with the angiographic severity of AI (Sellers). The transducer was placed on the left sternal border and the flow pattern was recorded at the aortic valve orifice and the proximal and distal left ventricular outflow tract (LVOT), using a strip chart recorder at a paper speed of 100mm/sec
The specific feature of AI was a widely dispersed dot pattern which began at the aortic valve closure and extended to late diastole. The severity of AI was graded by supravalvular aortogram in 25 patients. In grades I and II, the abnormal dot pattern due to AI was mostly detected at the aortic valve orifice and the distal LVOT, but it was rather difficult to detect the disturbed flow at the proximal LVOT. In contrast, in grades III and IV, the disturbed flow was recorded at all the sampling sites; with severe aortic regurgitation, it was detected at a wider range in the left ventricular cavity
In grades I and II, the abnormal dot dispersion at the proximal LVOT was not so large at its onset in diastole but it tended to increase after the mitral valve opening, whereas in the majority of patients of grades III and IV, a large dot dispersion was recognized from its onset to late diastole
The typical flow pattern due to AI was detected at the LVOT in 38 out of 41 patients (92.7%). Moreover, it was detected in all the patients with angiographically proved AI except for 1 case of grade I (96.0%)

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Circulatory responses to the upright tilt were studied in 20 normal subjects and 27 cardiac patients with ischemic heart disease or idiopathic cardiomyopathy
In normal subjects, the upright tilt caused obvious increases in heart rate and diastolic pressure, a slight decrease in systolic pressure and marked decreases in cardiac output and stroke volume
The circulatory changes during the tilt were less pronounced in the cardiac patients as compared with the normal subjects. The reductions of cardiac output and stroke volume and the increase in total peripheral resistance were all significantly diminished. A paradoxical increase in cardiac output during the tilt, an observation hitherto not well recognized, was observed in 5 cases with low cardiac index during the control period. Although several possibilities can be considered for the explanation of the diminished, sometimes paradoxical, circulatory responses to the tilt in cardiac patients, the improvement of the function of the diseased heart by preload reduction was proposed as an important factor
There was a significant negative correlation between the per cent changes of cardiac output and the per cent changes of PEP/LVET. It was suggested that the measurements of systolic time intervals during the tilt might be useful for evaluating the severity of the hemodynamic derangement in cardiac patients

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The left ventricular function curve was obtained in 14 patients with atrial fibrillation (af) by plotting the left ventricular stroke volume (SV) against end-diastolic volume (LVEDV) measured by echocardiography in 60-100 consecutive beats. Of the 14 patients, 7 had left ventricular failure due to a variety of cardiac abnormalities including CCM, perimyocarditis and AR. The other 7 patients with lone af who had normal LV function were used as normal controls
LV function curves in patients with ventricular failure were shifted downward and to the right of normal control curves. The slopes of LV function curves were decreased significantly in these patients
LV function curves shifted to the left and upwards and the slopes of the LV function curves were increased after treatment with digitalis and diuretics. In a patient with perimyocarditis and large pericardial effusion, LVEDV and SV were increased after treatment with diuretics alone, as a result of improved LV filling after disappearance of effusion. However, the LV function curve showed no shift and was situated on the extension of the curve before treatment
To know the effect of potentiation on LVEDV-SV relation in af, endsystolic LV pressure-volume ratio was derived approximately from direct brachial artery pressure at dicrotic notch (BAP(DN))/LVESV and com-pared with the relative degree of cycle-length change. There was a significant correlation between BAP(DN)/LVESV and preceding/prepreceding RR interval, representing the possibility that the relation between LVEDV and SV in af was influenced by so-called potentiation
Accordingly, LV function curve obtained from LVEDV-SV relation in af could be a modified function curve. Nevertheless, this reflects LV function documented by clinical symptoms and other widely utilized indices very well and is useful for assessing LV function

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The hypotensive effect of nifedipine (a Cal²⁺-antagonist) was studied in acute tests and during the long-term administration of the drug together with propranolol.
Nifedipine (10mg, sublingually) decreased blood pressure from 174/102 to 136/82mmHg with increase in heart rate and plasma renin activity. The combination of nifedipine (10mg, sublingually) and propranolol (0.2mg/Kg body weight, intravenously) decreased blood pressure from 168/104 to 131/86mmHg with decrease in heart rate and plasma renin activity.
Twenty-five hypertensive patients were treated with nifedipine and propranolol (10mg×3 to 4/day) together with or without diuretic for long-term. With the combination therapy, blood pressure of Group I (11 hypertensive patients with coronary heart disease) fell from 211/129 to 140/85mmHg, blood pressure of Group II (9 severe hypertensive patients without coronary heart disease) from 230/137 to 139/84mmHg, and blood pressure of Group III (5 established hypertension) from 182/107 to 134/83mmHg. With this treatment regimen, heart rate and plasma renin activity decreased, and abnormal electrocardiographic findings, hypertensive retinopathy, and renal dysfunction were improved.
Nifedipine, in combination with propranolol and a diuretic, is considered an effective treatment of hypertension either with or without coronary heart disease

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Peripheral blood lymphocytes from 31 normal subjects and 29 patients with heart diseases were stimulated by isoproterenol, and cyclic AMP level in lymphocytes was assayed. Simultaneously plasma norepinephrine concentration at rest was measured. In normal subjects the generation of cyclic AMP after the stimulation decreased with age. The response of lymphocytes in patients of NYHA classes III and IV was significantly smaller than in the normal, age-matched control. Plasma norepinephrine concentration of patients of classes II, III, and IV rose significantly above normal. In congestive heart failure, a significant correlation between plasma norepinephrine concentration and increase of lymphocyte cyclic AMP was demonstrated. From these results it was suggested that β-adrenergic receptors in congestive heart failure were desensitized

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The plasma concentrations of norepinephrine (NE), adenosine cyclic 3', 5'-monophosphate (cyclic AMP), and guanosine cyclic 3', 5'-monophosphate (cyclic GMP) were measured serially for 2 weeks after the onset of symptoms in 17 patients with acute myocardial infarction (AMI).
The mean concentrations of NE in patients without complications were significantly elevated during the first 2 days following AMI. There was a significant correlation between the maximum concentration of plasma NE and of plasma CK. The mean concentrations of plasma cyclic AMP and cyclic GMP in patients without complications were significantly elevated on the first day and for 8 days respectively following AMI. The concentration of plasma cyclic AMP on admission in patients with complications was significatly higher than that in those without complications. There were significant correlations between the maximum concentration of plasma cyclic AMP and those of plasma CK, GOT, and LDH. Significant but weak correlations between the concentration of plasma NE and those of cyclic AMP and cyclic GMP were found.
The results of the present study suggest an enhanced sympathetic nervous system activity at an early stage of AMI, a prolonged enhancement of parasympathetic nervous system activity in the course of AMI, and the potential value of plasma cyclic AMP concentration as a useful index to estimate the seriousness and size of AMI

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The coronary arterial lesions of Kawasaki disease are characterized by multiple stenoses and aneurysms, which might lead to myocardial ischemia, myocardial infarction, mitral insufficiency due to ischemic papillary muscle dysfunction, ventricular aneurysm, etc.
Eight children aged 6 to 13 years with Kawasaki disease underwent surgical treatments. These were coronary bypass surgery, coronary bypass surgery combined with right coronary aneurysmectomy and coronary bypass surgery combined with left ventricular aneurysmectomy. The postoperative course was smooth in all the patients. The selective angiography performed 1 month after the operation revealed the patency rate of 85% of the bypass grafts. However, 1 patient died suddenly during strenuous exercise 3 years after the surgery.
Several points to be considered in the aortocoronary bypass in the patients with Kawasaki disease are discussed. These include the unknown fate of saphenous vein grafts and the possibility of higher incidences of graft failure in the growing children. Since the long-term postoperative results are as yet not fully understood, close follw-up of the patients treated by aortocoronary bypass surgery would be mandatory

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In the perfused rat mesenteric vascular bed, the effects of captopril and prostaglandin I₂, (PGI₂) on the vasoconstrictor responses to norepinephrine or potassium chloride were studied. Captopril or PGI₂ in the perfusate attenuated the vascular responses to norepinephrine in a dose-related manner, while these substances had no effect on the vascular contractions induced by potassium chloride. In preparations treated with indomethacin, the inhibitory effect of captopril on the vascular response to norepinephrine was similar to that found in the untreated preparations. These results suggest that, although the effect of captopril on the vascular reactivity is similar to that of PGI₂, the direct vascular action of captopril is not mediated by the synthesis of prostaglandins in the vascular bed

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In order to investigate the direct metabolic effect of nitroglycerin on myocardium, its effect on mitochondrial free radical formation was studied in vitro, using the dog heart mitochondria impaired by ethanol. Free radical concentrations in state 4 respiration or the ratio of free radical concentrations in state 4 to state 1 was used as an index of mitochondrial function. Free radical concentrations were represented as ESR intensity.
In normal control, ESR intensity increased from 0.115±0.030 (mean±SD) per mg protein in state 1 to 0.178±0.017 in state 4 (p<0.001). When mitochondria were treated with 10-4M ethanol, on the other hand, ESR intensity decreased from 0.163±0.34 in state 1 to 0.137±0.019 in state 4 (p<0.05). When mitochondria were treated with 10^-6M nitroglycerin, in spite of the presence of 10^-4M ethanol, ESR intensity increased from 0.124±0.23 in state 1 to 0.153±0.024 in state 4 (p<0.05). ESR intensity in state 1 was increased by the treatment of ethanol (p<0.05), whereas ESR intensity in state 4 was decreased (p<0.001), and these effects were prevented by nitroglycerin (p<0.05). The ratio of ESR intensity in state 4 to state 1 demonstrated more remarkably the effects of ethanol and nitroglycerin. Ethanol reduced the ratio from 1.65±0.47 in the control to 0.86±0.13 (p<0.001) and the reduction was prevented by nitroglycerin to 1.25±0.23 (p<0.01).
It is concluded that nitroglycerin prevented the impairment of free radical formation of the mitochondria induced by ethanol, presumably by a mitochondrial membrane-stabilizing action

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Using the isolated and blood-perfused dog atrial preparation, chronotropic and inotropic responses to 3 kinds of alpha-adrenergic blockers, phentolamine, phenoxybenzamine, and E-643, were compared.
When phenoxybenzamine was administered into the cannulated sinus node artery, positive chronotropic and inotropic responses were induced in doses of 10-300μg. Phentolamine also produced positive responses, but at larger doses such as 100 and 300μg, accompanying initial negative responses.
E-643 usually produced only negative chronotropic and inotropic effects. Positive responses to phenoxybenzamine and phentolamine were significantly suppressed by propranolol, and negative responses to E-643 and phentolamine were not modified by atropine treatment.
From these results and previous reports, it is assumed that sinus tachycardia induced by alpha-blockers in situ may be due to 3 different mechanisms, i.e., 1) reflex tachycardia induced by the hypotension, 2) augmented catecholamine release mediated by the block of the presynaptic alpha-adrenoceptors, and 3) direct catecholamine release from locally innervated sympathetic nerve terminals

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Prophylactic effects of sulfinpyrazone (100mg/Kg), aspirin (5mg/Kg, 50mg/Kg), and propranolol (2mg/Kg, 10mg/Kg) on myocardial necrosis and hypertrophy induced by isoproterenol were examined. Drugs were administered to rats daily by gavage for a period of 2 weeks and after that isoproterenol (40mg/Kg) was injected subcutaneously. The control group received gavage of water and isoproterenol injection. The "no infarct" group received gavage of water and saline injection. Premedication of sulfinpyrazone and propranolol significantly preserved myocardial CK activity and decreased cardiac hypertrophy compared with control group (24 hours after isoproterenol injection) while aspirin did not have such effects. Myocardial cyclic AMP concentration significantly increased 30min after isoproterenol injection in control and all the premedicated rats compared with the "no infarct" rats. The increment of cyclic AMP was not suppressed by sulfinpyrazone and propranolol during this period. Plasma levels of prostaglandins were significantly suppressed by the administration of sulfinpyrazone and 50mg/Kg of aspirin, and were not suppressed by 5mg/Kg of aspirin.
In was concluded that premedication of sulfinpyrazone and propranolol reduced cardiac necrosis and hypertrophy induced by isoproterenol, but aspirin did not have such cardioprotective effects

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1. Alterations in troponin subunits in myocardial infarction were studied in the dog heart by the analysis of troponin-tropomyosin complex, i.e. native tropomyoin, of total structural proteins in SDS gel electrophoresis, and by the measurement of degree of activation of actomyosinATPase by Ca⁺⁺.
2. At 12 to 24 hours after coronary ligation, reductions in TN-C and tropomyosin were observed followed by a decrease in TN-I at 48 hours. The relative contents of these subunits were the lowest at 72 hours to 7 days falling to less than 10% of those in the non-ischemic myocardium. On the contrary, TN-T was preserved through the course of myocardial infarction.
3. Actomyosin-ATPase activity was increased at 12 to 24 hours after coronary ligation and then reduced rapidly at 24 to 48 hours together with the degradation of myosin. However, the activation of actomyosin-ATPase by Ca⁺⁺-troponin-tropomyosin was reduced already at 12 hours simultaneously with the reduction in TN-C, and almost completely lost at 48 hours.
4. Troponin subunits and actomyosin-ATPase activity returned to those of the control myocardium at 28 days after coronary ligation indicating the recovery of infarcted tissue

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Myocardial protection by dilazep HCl, an antianginal drug and a potent calcium antagonist, against myocardial damage following acute ischemia and reperfusion was studied with respect to myocardial contractility in isolated blood-perfused canine left ventricular muscle. Myocardial function was expressed by percent recovery rate of maximal net developed tension. 1) The coronary infusion of dilazep revealed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 2) The intravenous administration of dilazep to the support dog and Young's infusion also showed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. Dilazep showed no persistent depression of myocardial contractility due to its calcium antagonistic effect during reperfusion. 3) The combination of intravenous administration of dilazep to the support dog, Young's infusion, and hypothermia showed significant myocardial protection during prolonged ischemia and reperfusion even in hypertrophied ventricle. These results demonstrate that dilazep provides effective myocardial protection during ischemic arrest and repefusion by preventing abnormal calcium accumulation in myocardial cells during reperfusion. No persistent depression of myocardial contractility during reperfusion may support dilazep's clinical application as a myocardial protective agent in open-heart surgery

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An 18-year-old man had hypertension with hyperreninemia and marked difference in plasma renin activity between both renal veins after tilting. Selective renal arteriography revealed a stenotic lesion in a segmental artery to the upper pole of the left kidney with poststenotic dilatation. The upper pole of the kidney with abnormal arterial segment was resected and the blood pressure returned to normal. Electron microscopically, a large number of mature juxtaglomerular cell granules were associated with many protogranules in the epitheloid cell.
These findings suggest that his hypertension was due to overproduction of renin from the upper pole

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We studied the effect of angiotensin II analogue (AII-A) and angiotensin I converting enzyme inhibitor (SQ 14, 225) on blood pressure and the renin-angiotensin-aldosterone system in a patient with pseudo-Bartter's syndrome, who was a 26-year-old unmarried Japanese woman taking furosemide surreptitiously.
The intravenous infusion of AII-A decreased blood pressure from 85/35 to 68/28mmHg. This decrease in blood pressure was associated with an increment of plasma renin activity (PRA) and a decrement of plasma aldosterone concentration (PAC). Similarly, SQ 14, 225 given orally decreased blood pressure to the same extent. An increment of PRA and a decrement of PAC were also observed.
These results suggest that the renin-angiotensin system plays a considerable role in maintaining blood pressure in pseudo-Bartter's syndrome. Again, attention has to be paid to the possibility of surreptitious use of diuretics in an adult patient with persistent hypokalemic alkalosis, hyperactivity of the renin-angiotensin-aldosterone system and angiotensin II insensitivity simulating "true" Bartter's syndrome

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