In order to elucidate the role of the renin-angiotensin-aldosterone system and catecholamines in the pathophysiology of chronic congestive heart failure (CHF), a study was made of the relationship between these humoral factors and the hemodynamic parameters. In 36 patients with various degrees of CHF, urinary norepinephrine (U-NE) was significantly increased in Class III-IV (NYHA) patients with a positive correlation to total systemic vascular resistance (SVR) (p < 0.05) as well as to peripheral venous pressure (VP) (p < 0.05). Plasma renin activity (PRA) was increased in Class IV patients and tended to be positively correlated with SVR. Plasma aldosterone levels (PA) correlated well with PRA (p < 0.01). In six Class III-IV patients, the acute effect of oral angiotensin I converting enzyme inhibitor SQ 14225 (captopril) on mean arterial pressure (MAP), VP, PRA, PA and plasma catecholamines was examined. PRA was consistently increased (306%) and PA decreased (37%) following captopril administration, indicating that captopril effectively inhibited angiotensin 11 formation. MAP fell (17%), especially in two patients with mitral stenosis. The heart rate tended to decrease (7%). VP also fell (27%) with symptomatic improvement. The decline in VP correlated with the decrease in plasma norepinephrine concentrations (P-NE) (p < 0.01). In patients with mitral stenosis, urine volume decreased as blood pressure fell. In two patients with CHF refractory to conventional treatment, captopril induced increased urinary sodium excretion and body weight reduction despite only a slight fall in MAP and was useful as chronic unloading therapy. These results suggest that norepinephrine plays a role in elevating SVR as well as VP, and the renin-angiotensin system also appears to contribute to the rise in SVR in CHF when the circulatory impairment is more severe. Captopril seems to dilate arterioles by reducing angiotensin 11 levels and also to reduce VP by decreasing P-NE. It is a useful therapeutic measure in selected patients with severe CHF.

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Hemodynamic changes during the cold pressor test were examined in Type I labile (juvenile labile) hypertensive patients, Type II labile (middle aged labile) hypertensive patients, established hypertensive patients and normal subjects. In normal, Type I Iabile hypertensive and established hypertensive subjects, the pressor response during the test was accounted for chiefly by a rise in peripheral resistance. In Type II Iabile hypertensive patients, an increase in blood pressure during cold stimuli was accompanied by an augmented cardiac output. Therefore, Type II Iabile hypertension is separated clearly from other types of hypertension with respect to hemodynamic changes during the test. In Type II Iabile hypertensive patients, however, diazepam reduced an increase in cardiac output during the test, resulting in hemodynamic changes similar to those of normal subjects. After atropinization, the hemodynamic pattern of Type I and established hypertensives changed similar to that of Type II Iabile patients during the cold pressor test. It is concluded that an excessive cardiac output caused by the cold stimuli is a distinctive hemodynamic characteristics of Type II Iabile hypertensive patients, and this distinctive hemodynamic characteristics might be due to the decreased parasympathetic tone.

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The elevation of hematocrit is known to provoke myocardial ischemia in various clinical conditions. In order to clarify the effect of hematocrit and blood viscosity on coronary hemodynamics and oxygen utilization, isovolemic exchanges of blood with plasma or packed red cell were performed in ten open chest anesthetized dogs. Hematocrit was varied in the range of 20 to 60%. Coronary blood flow and cardiac output changed inversely with hematocrit. Coronary vascular resistance and blood viscosity elevated in logarithmic relation to hematocrit. Coronary vascular resistance and blood viscosity revealed linear relationship, the coronary vascular hindrance (resistance/viscosity) remaining constant for the hematocrit range of 20 to 60%. The arterial oxygen content increased linearly with the elevation of hematocrit, and the myocardial oxygen extraction rate was unchanged. The systemic oxygen transport rate increased with hematocrit. However, the left ventricular oxygen transport rate varied little, although the left ventricular oxygen transport at medium hematocrit was slightly higher than at low or high hematocrit. The myocardial oxygen consumption remained constant at each hematocrit, and the efficiency was high at low hematocrit in the face of the elevated cardiac output. The increase in hematocrit elevated the blood viscosity and played a significant role in determining the coronary vascular resistance. This could induce a disturbance in coronary microcirculation especially in pathological conditions.

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The response of the contractile and the series elastic elements to ischemia was studied with isometric contraction and quick release methods after measuring the passive length-tension relationship in glycerinated heart muscle fibers of dogs at resting state. Myocardial infarction was induced by ligating left coronary artery. Muscle fibers taken from the ischemic area three hours after ligation demonstrated reduction in maximal developed tension (P₀), the maximal rate of tension development (dp/dt_max) and V_max. The time to peak tension (t₀) was increased. As in fresh papillary muscle the modulus of elasticity of active glycerinated muscle increased in proportion to load. The stiffness of the series elastic element elevated significantly in ischemic muscle fibers. The passive stiffness in resting state showed a decrease in the slope accompanied by an increase in the intercept in ischemic heart muscle. Therefore, increased stiffness of the series elastic element and diminished contractility are present following acute myocardial infarction.

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The anterior descending branch of the left coronary artery (LAD) of the dog was ligated for 2 hours and thereafter reperfusion was continued for 1 hour. The regional myocardial blood flow (RMBF) during reperfusion was measured by a radioactive microsphere method. Whether a decrease in RMBF in the reperfused region could be prevented by injection of a calcium antagonist "diltiazem hydrochloride (diltiazem)" to LAD during reperfusion was simultaneously studied. RMBFs in ischemic epicardial (Epi) and endocardial (End) layers and End/Epi ratio 5 minutes after reperfusion were 1.87 ml/min/g, l.75 ml/min/g and 1.06 respectively, showing an increase in all values compared to the values in normal region. RMBFs in the Epi and End and End/Epi ratio 60 minutes after reperfusion were 0.99 ml/min/g, 0.91 ml/min/g and 1.05 respectively, showing a decrease in all values without occurrence of transmural flow gradient. The decrease in RMBFs in the Epi and End 60 minutes after reperfusion could be prevented by diltiazem to show 1.68 ml/min/g and 1.42 ml/min/g respectively which were within normal limits. RMBFs in normal Epi which could be perfused by diltiazem were 1.31 and 1.70 ml/min/g before and after injection of diltiazem while those in normal End before and after injection of the drug were 1.27 and 1.46 ml/min/g respectively; RMBFs in both layers could be increased by diltiazem, with the significant increase in RMBF of normal Epi to show a decrease in the End/Epi ratio after injection of the drug. The conclusions are as follows: (1) Diltiazem increases RMBF in normal myocardium. (2) The gradual decrease in RMBF after reperfusion can be inhibited by the drug so that myocardial injury may be reduced. (3) A possibility exists that clinically the drug is a promising agent for early revascularization.

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Acid phosphatase activity in the cerebral arterial system in spontaneously hypertensive rats (SHR) was cytochemically investigated. In the endothelial and medial smooth muscle cells, endoplasmic reticulums and Golgi complex revealed an intense acid phosphatase activity and primary lysosomes containing the high enzyme activity were found to be augmented in number. The enzyme activity was demonstrated in the vacuolated secondary lysosomes and in the intercellular spaces of the arterial walls. Lytic changes of the arterial mural cells and vessel matrix due to lysosomal enzymes were also evident. Causes of the lysosomal enzyme induction and roles of the enzyme in the developmental mechanism of hypertensive cerebrovascular changes in the SHR brain are discussed.

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