In the usual thin sections (4-7μ), myocardial fiber disarray in cases of hypertrophic cardiomyopathy (HCM) usually takes the form of marked cellular disarray. Its diffuse extent is specific for HCM, but its presence alone is not pathognomonic for HCM. In our previous report, we stated that thick sections (20-35μ) was quite adequate fro the study of structures of disorganized myocardial fibers. In the present paper, classification and an assessment of the distribution of myocardial fiber disarray were studied in hearts with HCM in 14 Japanese patients and in 45 hearts (25 normal hearts, 10 hearts with hypertension and 9 hearts with myocardial infarction) as the control, in the thick sections. In these thick sections, abnormal myocardial fiber disarray in HCM was classified into poorly-differentiated and well-differentiated fascicular patterns. Abnormal myocardial fiber disarray in most hearts with HCM comprised the former pattern and its extent was over 30% in all septums of hearts with HCM in comparison with less than 10% in the controls. The diffuse disarray was mostly noted in the middle three fifths in the septum, and in the outer and middle thirds in the free wall, where disarray was rare in the control hearts. These findings support the idea that diffuse disarray in the specific portions in HCM may be congenital and specific for HCM. The major focus of the disarray in HCM was the septum with symmetric hypertrophy. The disarray comprising two fascicular patterns involved a large number of fibers running in a vectorically perpendicular direction to the left ventricular cavity. Theoretically, shortenning of such fibers would make the wall thinner and the cavity larger, and lengthening would make the wall thick and the cavity small. Thus, a wall with a considerable number of such fibers would be hypofunctional. We conclude that diffuse disarray in the middle three fifths of the ventricular septum and in the middle and outer thirds of the ventricular free wall is fascicular, and that it is congenital, specific and one of the pathogenic factors for HCM.

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To determine whether clinical variables of coronary risk factors and electrocardiographic and scintigraphic findings could reliably detect the presence of coronary artery disease and of coronary stenosis in the individual coronary arteries, 11 clinical and 7 electrocardiographic and scintigraphic variables were compared with the findings of coronary angiography in 107 patients. Sixty-seven patients had angiographic evidence of coronary artery disease and forty did not. Exercise electrocardiograms were diagnostic in 43 patients (64%) and exercise thallium-201 scintigraphy in 56 (84%). A coronary scoring using all the above variables based on multiple discriminant analysis increased the diagnostic accuracy (sensitivity 96% and specificity 95%). This scoring system was applied to a prospective series of 59 cases with similarly selected patients. Fifty-five cases (93%) were correctly diagnosed. The coronary scoring system to assess the stenosis of individual arteries was less satisfactory and 51 cases (86%) of the right coronary, 51 (86%) of the left anterior descending and 44 (75%) of the left circumflex artery were accurately diagnosed. It is concluded that statistical multivariate analysis of clinical, electrocardiographic and scintigraphic variables facilitates the detection of coronary artery disease and that this scoring system is helpful assessing the probability of individual coronary artery involvement.

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In order to evaluate the usefulness of a stress Tl-201 myocardial scintigraphy in semiquantifying the myocardial perfusion, 10 normal subjects and 71 patients with coronary artery diseases were studied with sequential imaging over 3 hours. Myocardial to background ratio (M/B) in the exercise phase was significantly higher in the normal subject group than in the coronary artery disease groups. Three hours after exercise (redistribution phase), M/B decreased significantly in the normal subject group but remained unchanged in the coronary artery disease groups. Percent change of M/B with exercise was lower in the effort angina pectoris group (97±11.2%), and the old myocardial infarction group (101±14.5%) than in the normal subject group (127±12%). Sensitivity and specificity of this method were 93% and 47%, respectively. Out of 11 patients with variant angina pectoris, 9 patients showed positive scintigram. Of the 9, however, 6 cases were without organic coronary stenosis in the coronary angiography. There was a significant correlation between M/B on redistribution images (RD·M/B) and ejection fraction determined by left ventriculograms (r = 0.61, p<0.001), indicating a close relation between the amount of the residual viable myocardium and the left ventricular function. M/B and its percent change with stress Tl-201 myocardial scintigraphy reflect the myocardial perfusion and myocardial perfusion reserve and their semiquantitative analysis provides a useful means for detection of ischemic heart disease.

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Coronary artery diameters were analyzed in 13 patients with variant angina and in 12 control patients. Sequential coronary arterial angiography was performed during control periods, during attacks and after administration of nitroglycerin, and coronary vasospasm was documented during anginal attacks and accompanied by electrocardiographic changes in all 13 patients with variant angina. In 7 Patients (Group I) with variant angina, anginal attacks occurred more than 4 times a week, more than twice during the 3 days prior to coronary angiography and in the morning of coronary angiography. In another 6 patients (Group II) with variant angina, attacks occurred less than once a week and never occurred during the 3 days preceding the coronary angiography. Though the degree of coronary stenosis at the sites of spasm was not significantly different between Group I (52.9±23.4%) and Group II (38.3±27.3%) after administration of nitroglycerin, the percent stenosis in the lesions in Group I (77.9±14.1%) was significantly (p<0.01) higher than that in Group II (33.3±28.0%) in the control angiography. Therefore, the degree of stenosis observed in the control angiography decreased significantly (p<0.01) after administration of nitroglycerin in Group I (change in % : -25.0±19.8%), but not in Group II (change in % : 5.0±10.0%). In 12 patients with chest pain syndrome in whom coronary spasm was not demonstrated by infusion of ergonovine maleate, coronary stenosis at control angiography was not changed significantly after nitroglycerin administration. We conclude that coronary spasm appears to be present in the absence of angina event at the time of control angiography and to be closely related to the generation of the anginal attacks in patients with variant angina.

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To clarify the differences in response of blood pressure (BP) in the normotensives and the hypertensives (n = 30, 40±9 years, 142±17/91±14 mmHg, mean±SD), the subjects were divided into normotensives (N)(n =13, 34±5 years, 114±6/72±8 mmHg), prehypertensives (n = 8, 38±11 years, 125±6/80±3 mmHg), borderlines (n = 13, 38±10 years, 140±12/85±9 mmHg), and established hypertensives (n = 9, 43±6 years, 161±9/108±8 mmHg). BP and heart rate were measured in the supine position after a 30-min bed rest and the recovery phase following the double Master's two-step exercise. The rise in systolic BP was significantly greater in the prehypertensives and in the borderlines than in N, but was insignificantly smaller in the established. The rise in diastolic BP was significantly greater in all the groups of the hypertensives than in N. This rise was significantly greater in the borderlines than in the established. A multiple regression correlated significantly between the rise in BP and the resting BP (r = 0.467 in systolic, and r = 0.373 in diastolic). Diastolic BP following exercise increased in the hypertensives, but fell in N. The rise in heart rate was not significantly different between the hypertensives and N. The hyperresponse observed in both prehypertensives and the borderlines was diminished in the established hypertensives. These results suggest that the hyperresponse of BP may play an important role in the development of hypertension in the patients with essential hypertension.

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The effects of the converting enzyme inhibitor, SQ 14, 225, on the renin-angiotensin system, adrenal function and blood pressure were investigated in 14 hypertensive patients, i.e., 10 with essential hypertension (EH) and 3 with renovascular hypertension (RVH). The mean blood pressure (MBP) and plasma aldosterone showed significant decreases in the EH with normal renin (NR) group and in the RVH group but no significant changes in the EH with low renin (LR) group. Plasma renin activity (PRA) increased significantly in the EH with NR group and in the RVH group but showed no significant change in the EH with OR group. Significant correlations were found between the fall in MBP after SQ 14, 225 treatment and the pretreatment levels of PRA or plasma aldosterone. In an ACTH infusion study, the response of plasma aldosterone to ACTH revealed significant decreases after SQ 14, 225 administration. In an angiotensin II (A II) infusion study, the response of plasma aldosterone was unchanged after SQ 14, 225 administration. However, the pressor responses to A II infusion with SQ 14, 225 were significantly higher than those without SQ 14, 225. From these findings, it is concluded that the antihypertensive mechanism of SQ 14, 225 may be due mainly to the decrease in levels of endogenous A II and that the reduction in plasma aldosterone after SQ 14, 225 administration may be due to reduction of endogenous A II levels by converting enzyme inhibition.

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The developmental course of cerebrovascular diseases was examined by comparative neurological and pathological studies in stroke-prone SHR (SHRSP) which died spontaneously or were sacrificed. Behavioral status during their life span could be simply divided into 4 patterns, i.e., "no abnormalities", "irritable", "lethergic" and "akinetic" named Grades O, I, II and III, respectively (Yamori's Classification). Grades I, II and II of behavioral status corresponded well to symptomato-pathoanatomically divided 3 stages (relating to brain edema), i.e., Stages I, II and III, respectively.

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It has been assumed that ventricular standstill induces left ventricular dilation because filling continues without emptying. Left and right ventricular diameters by echocardiography and pressures were monitored continuously in 21 intact dogs before and during ventricular standstill induced by coronary embolization (E), potassium infusion (K⁺), or calcium infusion (Ca⁺⁺) in 7 dogs respectively. At the onset of ventricular standstill, left ventricular pressure rose from an end-diastolic of 4.6±2.2 to 16.6±3.6 mmHg after E, 5.4±3.2 to 18.0±3.3 mmHg after K⁺, and 6.3±2.1 to 16.6±3.6 mmHg after Ca⁺⁺ (all p<0.001). Left ventricular dimension rose from and end-diastolic of 44.6±8.0 to 49.4±8.5 mm after E, 43.1±5.1 to 46.3±4.6 mm after K⁺ but fell from 40.6±5.1 to 33.9±3.4 mm after Ca⁺⁺ before ventricular standstill occurred. During the first 5 min of ventricular standstill, left ventricular pressure gradually fell from 16.6±3.6 to 5.4±1.1 mmHg (E), 18.0±3.3 to 5.9±2.0 (K⁺), 16.6±3.6 to 5.5±1.7 (Ca⁺⁺) (all p<0.001) while left ventricular diameter gradually fell to 40.7±7.0 mm (E), 35.0±5.1 (K⁺), 29.6±3.6 (Ca⁺⁺) (all p<0.001). Right ventricular pressure initially rose from 2.9±1.6 mmHg to 12.1±3.1 (E), from 2.7±1.3 to 12.0±2.0 (K⁺) from 2.7±1.0 to 12.6±2.6 (Ca⁺⁺ within 15 sec, then gradually fell to 6.6±1.1 (E), 6.1±1.9 (K⁺), and 7.9±1.8 (Ca⁺⁺) in 5 min whereas right ventricular diameter rose progressively from 4.4±3.0 mm to 21.0±1.7 (E), 4.7±2.6 to 20.3±1.3 (K⁺), 4.2±1.1 to 18.1±2.8 (Ca⁺⁺) in 60 sec (all p<0.001). Thus ventricular standstill is characterized by early left ventricular emptying and inhibited left ventricular filling despite continued right ventricular filling, a finding that might reflect the different intrinsic properties of the two ventricles.

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This study was designed to clarify the mechanism of ischemia-induced mitochondrial dysfunction. Anesthetized 24 dogs were divided into 4 groups, which were premedicated with saline for the controls, lipid emulsion 1 ml/kg, DL-carnitine 300 mg/kg or dL-propinylcarnitine 100 mg/kg. Myocardial mitochondria were prepared from both ischemic and non-ischemic areas after 30 min of coronary ligation and their functions, the levels of acyl-CoA and free L-carnitine were measured. In the control group, acyl-CoA level in ischemic mitochondria increased significantly compared with that in non-ischemic mitochondria. Administration of lipid emulsion further increased acyl-CoA level in ischemic mitochondria, but premedication with carnitine or propionylcarnitine prevented the elevation of acyl-CoA level by increasing free L-carnitine level in mitochondria. Ischemic mitochondrial function was disturbed in the control group and premedication with lipid accelerated the dysfunction, while premedication with carnitine or propionylcarnitine reduced the dysfunction. There was a clear reciprocal correlation ( r = -0.98) between acyl-CoA level and mitochondrial function. These results indicate that accumulation of acyl-CoA is one of the important factors in ischemia-induced mitochondrial dysfunction.

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Three members of one family had cardiomyopathy of the congestive type. Autopsies of 2 brothers revealed marked dilatation of the left ventricle with diffuse interstitial fibrosis of unknown origin. The father's diagnosis was based on clinical findings. In one brother, a positive latex fixation test for rheumatoid factor had been documented when he were healthy. Another brother had a positive test for rheumatoid factor almost simultaneously with the onset of the disease. It remained positive until both died. Thus, the positive rheumatoid factor presumably reflected primary or independent immunologic defects rather than a secondary immunologic mechanism in these cases of familial congestive cardiomyopathy.

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