To evaluate the role of the autonomic nervous system, especially the parasympathetic nervous system, in the initiation mechanism of vasospastic angina pectoris (AP), the coefficient of R-R interval variation (CV) on the electrocardiogram (ECG) and plasma catecholamine concentration were measured in 25 patients with vasospastic AP, 10 patients with effort AP and 12 control subjects. CV which has been recognized as reflecting parasympathetic nervous system activity was calculated from 100 consecutive heart beats on the ECG and represented as the percentage of standard deviation of the R-R interval per mean R-R interval. Repeated measurements of plasma catecholamine concentration revealed higher values at any sampling point throughout a day in patients with vasospastic AP than those in control subjects. A distinctly higher CV was observed at night in the vasospastic AP group. This elevated CV was abolished by atropine sulfate (1.5mg/day per os). Pilocarpine injection (1.3mg/10kg B.W. subcutaneously) induced a marked increase in CV that preceded the occurrence of chest pain and/or ischemic ECG changes in 5 patients with vasospastic AP. The increment in CV at 10 min after pilocarpine administration was greater in vasospastic AP than in control subjects (p<0.05). It is concluded that enhanced parasympathetic activity may play a role in the initiation of coronary vasospasm associated with sympathetic hyperactivity.

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We studied the levels of thromboxane B₂ (TXB₂), 6-keto-prostaglandin F_1α (6-keto-PGF_1α), platelet aggregability, β-thromboglobulin and platelet factor 4 in 30 coronary artery disease (CAD) patients and 21 normal subjects during exercise. During treadmill exercise, 13 of 30 CAD patients reported chest pain. We administered a selective thromboxane synthetase inhibitor (OKY-046) for 2 weeks to 10 CAD patients with exercise-induced chest pain and studied its effects. At rest, the plasma TXB₂ levels and platelet aggregation were significantly lower in normal subjects than in CAD patients, and there was no difference between CAD patients with and without exercise-induced chest pain. On treadmill testing, plasma TXB2 levels and platelet aggregation increased significantly only in the CAD patients with exercise-induced chest pain. Plasma 6-keto-PGF_1α levels in normal subjects were significantly higher than those in CAD patients both at rest and during exercise. After administration of OKY-046, mean exercise time increased significantly from 7.5 to 8.6min (p<0.001). Plasma TXB₂ level and platelet aggregation decreased significantly after OKY-046 administration both at rest and during exercise.
These results suggest that a marked increase in TXA₂, with only a minimal change in PGI₂, during exercise may contribute to exerciseinduced myocardial ischemia, and that OKY-046 is useful in the treatment of CAD patients.

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Systemic and coronary hemodynamic effects of acebutolol (10mg i.v.), a cardioselective β-adrenoceptor blocking agent were investigated in 11 patients with coronary artery disease and significant arterial obstructive lesions. Efficacy was assessed by simultaneous left and right heart catheterization and with an inlaying Webster thermodilution catheter in the coronary sinus. The data were compared with data from 7 other patients who received 2mg i.v. of propranolol, a non-cardioselective β-blocker. With acebutolol, (1) the heart rate was reduced significantly (p<0.01), (2) no significant changes were observed in the LVSP, LVEDP, mean PWP, LVmax dp/dt/p, LV negative dp/dt/p, CI, SWI and SPI, (3) CSF and MVO₂ decreased significantly (p<0.01) 5min after injection and (4) the CVR showed a significant elevation (p<0.05) after 5min. With propranolol, (1) the heart rate decreased significantly (p<0.05), (2) there were no significant changes in LVSP and LVEDP, (3) the mean PWP increased significantly (p<0.05), (4) the LVmax dp/dt/p, CI and SWI decreased significantly (p<0.05), (5) the CSF and MVO₂ decreased markedly (p<0.01) and (6) the CVR increased markedly (p<0.01).
Was compared to the effects of 2mg i.v. of propranolol, those produced by acebutolol (10mg i.v.) were characterized by a predominant negative chronotropic action with minimal negative inotropic action, combined with a reduction in CSF and MVO₂. The findings suggest that the efficacy of acebutolol in pump failure caused by myocardial ischemia during effort angina is mediated by improvement of the myocardial oxygen demand-supply imbalance.

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The clinical features and cardiopulmonary function of 5 patients with atrophic heart in Duchenne muscular dystrophy (DMD) were studied by echocardiography and spirometry. Atrophic heart was defined as a state where the left ventricular end-diastolic volume decreased markedly during long-term follow-up (over 5 years). The patients with atrophic heart were more emaciated and showed more severe motor disability than the controls (18 DMD patients with a normal left ventricular cavity size). The pre-ejection period/ejection time ratio was significantly higher in patients with atrophic heart than in controls, and the maximal diastolic posterior wall velocity was reduced. The forced vital capacity was lower in patients with atrophic heart than in controls, but the onesecond forced expiratory volume rate was similar in the 2 groups. Three patients with atrophic heart died. Examination at autopsy showed that their hearts were small and of low weight, and showed not only fibrosis, but also brown atrophy and waxy degeneration. These findings indicate that cardiopulmonary function is significantly reduced in DMD patients with atrophic heart.

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White blood cell (WBC) Na⁺ and K⁺ concentrations, plasma (Na⁺+K⁺)ATPase inhibition and blood pressure were determined in normotensive control subjects and patients with essential hypertension. While the untreated hypertensive group had significantly lower WBC K⁺ concentrations than the normotensive group (mean±SEM, 121.6±4.4vs. 134.7±2.8mEq/kg, p<0.05), no significant difference was observed in WBC Na⁺ concentrations between the 2 groups. The mean of plasma (Na⁺+K⁺)ATPase inhibition in untreated hypertensive patients was higher than that in normotensive controls (14.8±1.7vs. 7.2±1.8%, p<0.05). The correlations between (Na⁺+K⁺) ATPase inhibition and mean blood pressure and between WBC Na⁺/K⁺ ratio and mean blood pressure were significant (r=0.278, p<0.05 and 0.270, p<0.05, respectively), but both were weak. However, untreated hypertensive patients with higher (Na⁺+K⁺)ATPase inhibition had significantly higher WBC Na⁺/K⁺ ratios than untreated patients with less (Na⁺+K⁺) ATPase inhibition. These results suggest a contribution of plasma (Na⁺+K⁺) ATPase inhibition in the production of high blood pressure in a subset of patients with essential hypertension, which results in altered intracellular K⁺ concentrations.

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The relationship between the location of an accessory pathway and body surface EGG waveforms was investigated by computer simulation of the WPW syndrome using a human heart model. The 3-dimensional heart model is composed of 50, 000 units so as to represent the details of ventricular excitation. Ten typical accessory pathways near the A-V groove were examined, which correspond to Gallagher's classification of the WPW syndrome based on their surgical experience. Twelve-lead ECG waveforms were calculated for these 10 cases and were compared with the clinical observations of Gallagher et al. The polarities of the delta waves at 40msec after the onset of the QRS were listed. The agreement of our model with the clinical data obtained by Gallagher et al is 87%. Details of changes in the ECG waveforms were also examined by changing the terminal location of the accessory pathway along the radial and longitudinal directions in the ventricles, and it was found that the ECG waveforms of the limb leads are more sensitive to this difference in the preexcited location than those of the chest leads. The simulated epicardial isochronic patterns also agree with the measurements.

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We studied the effects of Ca channel blockers and 3 antiarrhythmic drugs on the digitalis-induced oscillatory afterpotential (OAP). The OAP was observed in Purkinje fibers stimulated by pulse trains, with cycle lengths ranging from 1, 000 to 300msec. The Ca channel blockers verapamil, diltiazem and nifedipine (2.0×10^-6M) depressed OAP significantly and abolished triggered activity. Verapamil was more effective than diltiazem. However, nicardipine and nitrendipine (2.0×10^-6M) had no depressant effects on OAP or triggered activity. The antiarrhythmic drugs procainamide (1.0×10^-4M), mexiletine (1.0×10^-5M) and propranolol (1.0×10^-4M) depressed both OAP and triggered activity. There were no significant differences in the depressant effects between the Ca²⁺ antagonists (except for nitrendipine and nicardipine) and the other antiarrhythmic drugs. The OAP coupling interval was prolonged by verapamil, diltiazem, propranolol, procainamide and mexiletine. Although the APD50 was shortened by verapamil, diltiazem and nifedipine, it was prolonged by propranolol. It is concluded that nifedipine, verapamil, diltiazem, procainamide, mexiletine and propranolol may be effective for digitalis-related arrhythmia.

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The myocardial protective effect of nicorandil, N-(2-hydroxyethyl) nicotinamide nitrate ester, against hypoxia was examined in comparison with that of nitroglycerin in 22 open chest dogs. The regional ventricular myocardium was perfused for 5 min with a hypoxic solution in 8 dogs (Group 1), with a hypoxic solution containing 0.5 or 2.5mg/dl of nicorandil in 7 dogs (Group 2) and with a hypoxic solution containing 0.5mg/dl of nitroglycerin in 7 dogs (Group 3). In Group 2, the ATP content of the hypoxic myocardium was 3.14±0.37μmol/g, which was less than that in the uninvolved myocardium (4.31±0.57μmol/g) but significantly higher than those of the hypoxic myocardium in Groups I and 3 (2.09±0.45 and 2.39±0.33μmol/g, respectively). The lactate content of the hypoxic myocardium in Group 2 (5.05±1.13μmol/g) was less than those of the hypoxic myocardium in Groups 1 and 3 (8.77±2.34 and 8.98±2.08μmol/g, respectively). This protective effect was not caused by the hemodynamic changes. In contrast, nitroglycerin did not show any protective effects on the hypoxic myocardium.

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To examine the effects of diltiazem on myocardial ischemia, 200μg/kg of diltiazem were injected intravenously into anesthetized openchest mongrel dogs 10min after coronary ligation. This was followed by a continuous infusion of diltiazem at 10μg/kg/min for 50min. Regional myocardial blood flow (MBF) was measured by the hydrogen gas clearance method. Sixty minutes after ligation, myocardial specimens were taken from the areas where MBF was measured, and the ATP and CP contents were determined by the bioluminescence method. Simultaneously, mitochondria were isolated from the ischemic and nonischemic areas, and both the respiratory control index (RCI) and the rate of oxygen consumption in state III (QO₂ III) were calculated.
The aortic systolic pressure and heart rate of diltiazem treated and untreated dogs were not significantly different, and diltiazem did not increase the MBF in the area with a MBF below 40ml/min/100g. When MBF was 10 to 30ml/min/100g, the ATP content in the diltiazem treated hearts was significantly higher than that in the untreated dogs, whereas the CP content was not significantly changed.
Thus, diltiazem administered after ischemia preserved ATP content in the ischemic myocardium with a MBF of 10 to 30ml/min/100g without significantly affecting the hemodynamics or MBF. This suggests that diltiazem exerts a cardioprotective effect by acting directly on the ischemic myocardium if it has an MBF above a certain level, even when the drug is administered after the onset of ischemia.

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We assessed the accuracy of the intraventricular balloon method of left ventricular volume measurement with all chordae tendineae intact and then severed. The space between the endocardium and the balloon is the source of the volume measurement error. We assessed the volume errors at different intra-balloon pressures between 50 and 250mmHg, using formalin fixed canine left ventricles. The volume error with all chordae tendineae intact was significantly greater than with all chordae tendineae severed at any balloon pressure. The difference of the volume errors under these two conditions amounted to 1.9-3.3ml regardless of intra-balloon pressures. We visually confirmed that this difference predominantly originated from the space behind the tense chordae tendineae.

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The effects of vanadate on the vascular smooth muscle of Wistar Kyoto rats (WKY) and stroke prone spontaneously hypertensive rats (SHRSP) were examined. It was shown that sodium vanadate caused contraction of the aortae, mesenteric and basilar arteries of both strains, and that the reactivity was higher in SHRSP in the aorta and mesenteric artery. The vanadate-induced contractions were not blocked by 6-hydroxydopamine, adrenergic blocking agents, indomethacin or ouabain, while 4, 4'-diisothiocyano-2, 2'-disulfonic acid stilbene did. An increase in K⁺-concentration potentiated the vanadate-induced contractions of the mesenteric arteries and minimized the difference between preparations from WKY and SHRSP. In depolarized preparations incubated in KTyrode's solution (140mM KCl), vanadate induced phasic contractions followed by marked relaxation in the aortae of both species, the relaxation being more prominent in SHRSP aorta, while depolarized mesenteric arteries showed sustained contractions. It was revealed that vanadate caused contractions by acting inside the cell, and membrane permeability to vanadate might be higher in the vascular smooth muscle of SHRSP. The findings also suggested that vanadium, an inorganic element, can be involved in the initiation of hypertension in SHRSP when it acts on vascular smooth muscle.

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The effects of piretanide and furosemide on systemic arterial blood pressure and heart rate were examined in the anesthetized dog and the effects on atrial rate and contractile force were assessed in isolated atrial muscle perfused with heparinized arterial blood from a donor dog. When piretanide was administered intravenously to intact dogs, the depressor and bradycardic responses were produced dose-dependently. There were no significant simultaneous chronotropic or inotropic changes in the isolated atrium. On the other hand, furosemide (1-3mg/kg) did not induce significant changes in either systemic blood pressure or heart rate in the intact dog. The atrial rate and developed tension were also not affected in the isolated atrium. A potent beta-adrenoceptor blocking agent, propranolol (1mg/kg i.v.), consistently produced a significant depressor response and a profound negative chronotropic effect in the intact dogs; significant negative chronotropic and isotropic effects were also observed in the isolated atrium. When large doses of piretanide and furosemide were injected intraarterially into the sinus node artery of the isolated atrium, atropine-insensitive negative chronotropic and inotropic effects were induced dose-dependently. The potency of the negative chronotropic effect of piretanide was slightly greater than that of furosemide, but the negative inotropic effect of piretanide was slightly smaller than that of furosemide. These data indicate that piretanide has a depressor effect without significant cardiac influences. However, a high dose of piretanide has negative chronotropic and inotropic effects. These effects were not observed with the doses of furosemide (1-3mg/kg) employed in this study.

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A highly symptomatic 20-year-old woman with rheumatic mitral valvular stenosis was referred for cardiac catheterization. Following the procedure it was decided to perform a mitral valvuloplasty with a balloon catheter. An isolated transarterial approach through the right femoral artery was used. A Sones catheter was introduced into the left atrium and through it a long teflon-coated guide wire was placed into this cavity. The Sones catheter was removed and an 18mm diameter balloon catheter was placed under the mitral valve and inflated several times for about 15 sec each. The pulmonary wedge and pulmonary artery pressures were significantly lower than the pre-valvuloplasty ones. The angiograms showed better mitral valve opening.

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A 37-year-old woman was admitted with an acute anterior myocardial infarction. Coronary arteriography revealed a dissecting aneurysm of the left main coronary artery. The patient died from perioperative myocardial infarction following aortocoronary bypass surgery on the 102nd hospital day. Histologic sections of the aneurysm revealed that granulation tissue had replaced the aneurysm, suggesting spontaneous healing of the dissecting aneurysm.

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A rare case of multiple infarction is described. An abnormal Q wave due to an old anteroseptal infarction was completely masked by a new contralateral posterior myocardial infarction. Coronary angiogram revealed multiple stenoses of segments 1 (100%), 7 (99%), 12 (90%) and 13 (99%). Left ventriculography also showed akinesis of segments 2, 3, 4 and 6, and reduced wall motion in segments 1, 5 and 7. These findings, together with electrocardiographic changes from before the present attack reinforce the above interpretation.

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