Myofiber changes in idiopathic cardiomyopathy were examined by the scanning electron microscope in order to elucidate the three-dimensional architecture. Muscle specimens were sampled from the ventricular walls of 13 autopsy cases (7 with the congestive type, 3 with the hypertrophic type and 3 controls), and observed according to the Evan's method. In addition, the same samples were investigated histopathologically using the tribasic staining originated by Kurotaki, and the muscle cell diameters were analyzed with a pendigitizer computer system. In congestive cardiomyopathy, the hypertrophic myofibers branched more frequently and varied more in thickness than in the controls. The complex myofiber architecture seemed to be the result of the compensation for muscle weakness. On the other hand, hypertrophic cardiomyopathy revealed three-dimensional myofiber disarray, which was fundamentally constituted from a ring formation of the myofiber branches, but only at the ventricular septal wall. The structure appeared only to promote muscle stiffness.

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The study of re-entry phenomenon during the right ventricular extrastimulus method was performed on 22 patients using 10 polar electrode catheter. Two to 4 spikes from the specialized conduction system were recorded in response to the premature extrastimulation (S2). By using this catheter, the catheter position was defined more clearly than the other reports. From the patterns and sequence of spikes in response to S2, the routes of impulse propagation were studied. In 17 cases whose patterns of spikes were different from those of antegrade conduction, the impulse from S2 seemed to be retrogradely conducted via the left bundle branch (LBB) to the branching portion and thereafter conducted bidirectionally both to His bundle (HB) and the right bundle branch (RBB) (HPS re-entry). In 6 cases whose patterns of spikes were similar to those of antegrade conduction, the impulse from S2 was retrogradely conducted via RBB to HB and turned in some portion above HB and antegradely traveled to the ventricle. In one case who was diagnosed as concealed WPW syndrome, the pattern of spikes showed 2 types of re-entry as described above. The mechanism of the ventricular re-entry was able to be classified into 2 types from the patterns and sequence of spikes in response to S2.

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An attempt was made to evaluate a thrombotic tendency in cases of infective endocarditis (IE) from the viewpoint of the changes of platelets and coagulofibrinolysis. Qualitative changes of platelets by thrombi formation were detected by showing activated responses of platelets to adenosine diphosphate or collagen and by showing a high level of plasma β-thromboglobulin which is released by platelets during aggregation. A mild hypercoagulable state without acceleration of fibrinolysis was also detected by showing low levels of plasma antithrombin III which is the most potent antithrombin in the blood and normal levels of plasma α₂ -plasmin inhibitor in the blood. From above findings, it was concluded that a thrombotic tendency in cases of IE was clearly detected by qualitative changes of platelets by thrombi formation and by mild hypercoagulability without acceleration of fibrinolysis.

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To clarify the hemodynamic effects of prazosin in congestive heart failure, the changes of blood distribution were examined radiocardiographically in 9 patients. After obtaining control data, patients were given oral prazosin (5.9 ± 2.6 mg/day) for 3 weeks. Studies were repeated immediately before and one week after the cessation of the prazosin treatment. Cardiac index (CI) and stroke index (SI) showed significant increases, and mean blood pressure (MBP) and peripheral vascular resistance significant decreases as compared with the control values. However, heart rate did not change significantly throughout the period of this study. After stopping prazosin, MBP, CI and SI returned to the control levels. Concerning the changes in blood distribution, total blood volume and body blood volume significantly increased during prazosin therapy. Pulmonary blood volume (PBV) had a tendency to increase, although the changes were not significant. In patients, in whom the PBV increased during prazosin treatment, diuretics had to be used concomitantly. Our results show that prazosin is effective in the treatment of congestive heart failure and radiocardiography is a useful non-invasive procedure in assessing cardiac improvement and in designing the appropriate treatment.

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This experiment was designed to determine the optimal flow rate during early reperfusion after ischemic arrest for one hour at 28°C of myocardial temperature, assessed by cardiac function, biochemistry and fine structure of the left ventricle. Under cardiopulmonary bypass (CPB) at a flow rate of 80 ml/kg/min, the ascending aorta was clamped for one hour at 28°C of myocardial temperature in 19 mongrel dogs. After the aorta was declamped, the perfusion pressure was maintained at 50 mmHg and dogs were divided into 3 groups by flow rate of 50 (Group A), 80 (Group B) and 150 ml/kg/min (Group C) for 15 min of reperfusion. The left ventricular function was measured and calculated before the institution of CPB and 30 and 60 min after the declamping of the aorta. Myocardial isoenzymes (m-GOT, MB-CPK) in the coronary sinus venous blood were measured. Myocardial adenosine triphosphate (ATP), creatine phosphate (CP) and water content were measured by the samples of the epicardial and endocardial layers of the left ventricle and the ventricular septum at the end of experiment. The subendocardium of the left ventricle was examined by electron microscopy. Mortality rates were 1/6 (16.7%) in Group A, 2/7 (28.6%) in Group B and 4/6 (66.7%) in Group C. The myocardial water content was the lowest, and ATP was significantly higher in Group A compared to others. Left ventricular endodiastolic pressure was the lowest and the ultrastructure was well maintained in Group A. These data suggest that a high flow rate is detrimental to myocardial recovery during early reperfusion, and the optimal flow rate during early reperfusion after ischemic arrest (60 min, 28) appears to be 50 ml/kg/min.

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In order to elucidate the mechanism of blood pressure elevation in the patients with borderline hypertension, the sympathetic nervous activity was investigated and the following results were obtained: 1) Plasma catecholamine (CA) levels were elevated in young men but not in middle-aged men with borderline hypertension in comparison with age-matched normal men. 2) Cardiovascular responsiveness to exogenous CA was not augmented in young men with borderline hypertension. 3) Cerebrospinal fluid noradrenaline levels were elevated in young men with borderline hypertension. They correlated positively with plasma NA or blood pressure. 4) In young men with borderline hypertension, plasma and urinary CAs Were not altered by hypertonic saline loading. These results suggest that increased activity of the central and peripheral sympathetic nervous system is an important mechanism of blood pressure elevation in young subjects with borderline hypertension.

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In order to clarify the role of dopamine on the pathophysiology of essential hypertension, mean arterial pressure (MAP), heart rate (HR), urine volume (UV), urinary sodium excretion (UNaV), endogenous creatinine clearance (Ccr), fractional excretions of sodium (FENa), inorganic phosphorus (FEP) and potassium (FEK), plasma renin activity (PRA), plasma aldosterone concentration (PAC) and plasma noradrenaline concentration (PNA) were measured before and after intravenous infusion of dopamine (3 μg/kg/min, 60 min) in normotensive (NT) and essential hypertensive subjects (EHT). Following dopamine infusion, a significant decrease of MAP and an increase of HR were observed in EHT but not in NT. UV, UNaV, Ccr, FENa, FEP and FEK increased significantly in both NT and EHT, and changes in these except for Ccr were significantly greater in EHT than in NT. In EHT, following dopamine infusion, PNA was clearly elevated, but no remarkable change was found in PRA and PAC. A significantly positive correlation was found between UNaV and FENa or FEP, and between FENa and FEP, while no significant relation was observed between UNaV and Ccr, MAP or MAP before dopamine infusion. A significant inverse correlation between supine PRA before dopamine infusion and FENa or FEP and a positive correlation between age and FENa or FEP were also observed in these patients. The changes in UNaV positively correlated with FENa and FEP in both low renin (group L) and normal renin EHT (group N) and with Ccr in group N but not in group L. The mean values of FENa, FEP and FEK were significantly higher in group L as compared with those in age-matched group N. These results suggest that, since the enhanced response to infused dopamine may reflect reduced dopaminergic activity, attenuation of renal dopaminergic activity might exist and be involved through a disturbance of water-sodium metabolism, at least in part, in the pathophysiological mechanism in EHT, particularly in group L.

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Altered prostacyclin metabolism may underlie essential hypertension. In this study, responses of plasma 6-keto-prostaglandin F₁α (6-keto-PGF₁α: a stable metabolite of prostacyclin) to infused norepinephrine (NE) were compared in 14 normotensive subjects (NT) and 20 untreated patients with essential hypertension (EH). In addition, changes in systemic hemodynamics following NE-infusion were compared with changes in plasma 6-keto-PGF₁α. The subjects were all hospitalized and placed on a diet containing 6-8 g of salt per day. Blood pressure was recorded directly through the brachial artery, cardiac output (CO) was determined with the dye-dilution technique using cuvette and total peripheral vascular resistance (TPR) was calculated before and 60 min after NE-infusion. Arterial plasma 6-keto-PGF₁α was also determined before and after NE-infusion. The rate of NE-infusion was adjusted to elevate mean arterial pressure (MAP) by I 0-15%. Plasma 6-keto-PGF₁α was radio-immunoassayed. Elevation of MAP was 13.0 1.2 (SE) in NTs and 11.7 1 .4% in EHs. After NE-infusion, CO and TPR both significantly increased in NTs, while only CO increased significantly in EHs. Changes in CO and TPR were both significantly different between the two groups (p < 0.01). Initial plasma 6-keto-PGF₁ was reduced in EHs as compared with NTs (1 74 15 vs 295 41 pg/ml, p < 0.02). However, during NE-infusion, the increase in plasma 6-keto-PGF₁ was greater in EHs than in NTs (p < 0.0 l). There was a significant negative correlation between changes in TPR and plasma PG (r = -0.36, p < 0.05). The results indicate that responses of systemic hemodynamics and plasma 6-keto-PGF₁ to infused NE are different in the NT and EH groups, and that the absence of changes in TPR in EHs may be related to a marked increase in circulating prostacyclin. These findings, together with the reduced initial levels of plasma 6-keto-PGF₁ in EHs, probably represent altered prostacyclin metabolism in essential hypertension.

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Tritium labeled leucine was used to investigate the effect of sodium intake on renin biosynthesis. This labeled amino acid was incubated with renal cortical slices from mice which were fed on low, basal and high sodium diets and its incorporation into the renin molecule was investigated. Renin was extracted from the incubated slices and then precipitated with rabbit anti-mouse submaxillary renin serum followed by the addition of goat anti-rabbit IgG serum. The radioactivity incorporated into the renin was 0.07 to 0.22% of that found in the soluble protein. The radioactivity incorporated into renin was increased with incubation time at nearly linear rate and it was decreased by the addition of puromycin or of large amount of unlabeled leucine into the incubation medium. The specific activities of radioactive renin in slices from both mice fed a low sodium and high sodium diet were the same. However, the total radioactivity in renin of the slices from mice fed with low sodium diet was higher than that from mice fed with high sodium diet. This indicates that the production of renin in the mice on low sodium diet was accelerated as compared to that in mice on high sodium diet. The results suggest that change of sodium balance affects the biosynthesis of renin which can lead to changes of renal renin content and its release from the kidney.

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Electrolyte concentrations in the erythrocytes, serum and 24-hr urine were measured in 34 untreated essential hypertensives (EH), 32 normotensives with a family history of hypertension (N^&oplus;), 112 nomotensives without a family history of hypertension (N^&ominus;), 76 senior high school students with high blood pressure (H) and 110 students with normal blood pressure (C). For the measurement of intra-erythrocyte electrolytes, a new method to decrease the trapped plasma was developed and adopted. A new simple method to collect 24-hr urine was devised, too. The results were as follows: 1) The sodium concentration [Na] and the ratio of [Na] to potassium concentration [Na/K] in the erythrocytes were significantly higher in the EH and N^&oplus; than in the group of N^<ominus;gt; (p < 0.01). 2) There was a positive correlation (r = 0.43) between the [Na/K] in the serum and erythrocytes in the 3 groups. The [Na/K] value in the erythrocytes to a given [Na/K] value in the serum was higher in EH than in the group of N^&ominus;. 3) When the group of H was compared with C, the Na excretion of the 24-hr urine in the former group was found to be slightly higher, and the [Na/K] of the 24-hr urine and the [Na] and [Na/K] values of the erythrocytes were significantly higher, too. It may therefore be said that an increase in the intracellular [Na] or [Na/K], which may be caused genetically, and an excess of Na intake and an increase of the ratio of Na/K intake are presumed to play an important role in the pathogenesis of essential hypertension.

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The site of action in the steroidogenic pathway of aldosterone stimulating factor (ASF), isolated from human urine, was studied in collagenase-dispersed rabbit adrenal capsular cells and compared with those of β-lipotropin (β-LPH), angiotensin II (A II) and adrenocorticotropic hormone (ACTH). When incubated with adrenal cell suspension at 37°C for 2 hours, ASF, β-LPH and ACTH induced dose-related increases in aldosterone production. ASF was less potent (ED₅₀ = l0^-9M) than ACTH but was more potent than β-LPH. When ASF was added to the incubation with low dose of A II or ACTH, its effect on aldosterone production was additive, while no additional effect of ASF on aldosterone production was obtained in the presence of high dose of A II or ACTH. ASF increased the conversion of corticosterone to aldosterone like ACTH and β-LPH. We have reported that ASF is s true aldosterone secretagogue and readily distinguishable from ACTH, A II and β-LPH. The present study suggests ASF shares a common rate-limiting final pathway of steroidogenesis, which may be the step between corticosterone to aldosterone, with ACTH, A II and -LPH .

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Intracisternal injections of hypertonic NaCl elicited the pressor responses in urethane anesthetized spontaneously hypertensive and normotensive Wistar rats. The intracisternal pretreatment of 1-Sar-8-Ile-angiotensin II, angiotensin II analog, could abolish the pressor responses to intracisternal injections of 5% NaCl in urethane anesthetized spontaneously hypertensive rats, while basal blood pressure was not affected by these pretreatrnent. Both intracisternal and intravenous administration of captopril, an angiotensin I converting enzyme inhibitor, did not alter the pressor effect of hypertonic NaCl in normotensive rats. Basal blood pressure was lowered by intravenous injection of captopril. The involvement of angiotensin II in the pressor mechanism of hypertonic NaCl was confirmed by the enhanced pressor responses to intracisternal injections of 5% NaCl in urethane anesthetized rats pretreated intracisternally with angiotensin II. These findings suggest that angiotensin II itself could play an important role in the pressor responses to intracisternal injections of hypertonic NaCl without involving a converting enzyme system.

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A low sodium diet for 7 days in the rat induced an enhancement of the vascular effects of bradykinin, determined as the blood pressure response, by 56%. However, this enhancement reverted after 28 days of a low sodium diet. A sustained increase in the number of uterine smooth muscle bradykinin receptors during low sodium diets was observed, 1.3 times of the control on the 7th day and 1.7 times on the 28th day. No change in binding affinity was found in any of the studies. These results suggest that the vascular effects of bradykinin after low sodium diets may be regulated by homeostatic mechanisms via the change in the number of vascular smooth muscle bradykinin receptors at subcellular levels, and that the number of uterine smooth muscle bradykinin receptors may be affected by sodium status per se.

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