Radionuclide angiographic measurements of left ventricular ejection fraction were performed at rest and during exercise in 10 normal persons and 11 patients with coronary artery disease. Exercise was continued on a supine bicycle exercise table up to a symptom-limited maximum. Plasma levels of atrial natriuretic peptide (ANP) were also determined at rest and during exercise.
Ejection fraction in the normal volunteers was 59±3% (mean±SEM) at rest and increased significantly (p<0.01) to 69±3% during exercise. Ejection fraction in the patients was 47±5% at rest and did not change significantly during exercise (51±7%). Plasma ANP in the normals rose significantly (p<0.01) from 62±16pg/ml at rest to 454±94pg/ml during exercise. Plasma ANP in the patients also rose significantly (p<0.01) from 231±102pg/ml to 794±170pg/ml. The response of plasma ANP to exercise was enhanced significantly (p<0.05) in the patients as compared with the normals in relation to ejection fraction by analysis of covariance. In both the normals and the patients, plasma ANP was inversely and significantly correlated with ejection fraction during exercise (r=-0.46, p<0.05, n=21), however, not at rest. Because it has been reported that plasma ANP is correlated positively with pulmonary artery wedge pressure, the estimation of plasma ANP during an exercise stress test might be used for the evaluation of cardiac reserve in coronary artery disease.

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Acute effects of dibutyryl cyclic AMP (DBCAMP) on hemodynamics, renal circulation and plasma catecholamine levels were examined in 8 patients with congestive heart failure, NYHA functional class II or III. Before and during intravenous infusion of dibutyryl cyclic AMP at 0.1mg/kg/min for 30min, hemodynamic variables, renal blood flow (RBF) and plasma catecholamine levels were investigated. 1) DBcAMP increased the cardiac index from 2.69±0.65 to 3.60±0.84liter/min/m² (+33.8%, p<0.001) and heart rate from 70.9±14.3 to 84.1±15.7bpm (+18.6%, p<0.001) and decreased mean aortic pressure from 91.8±11.3 to 82.5±9.8mmHg (-10.1%, p<0.001), and systemic vascular resistance from 1843±570 to 1263±370 dynessec-cm^-5 (-31.6%, p<0.001). 2) RBF increased from 335±81 to 517±188ml/min (+54.3%, p<0.05) and renal vascular resistance decreased from 2.33±0.61 to 1.52±0.68×10⁴ dynes-sec-cm^-5(-34.5%, p<0.001). 3) Plasma norepinephrine levels increased significantly.
The results indicate that DBCAMP is useful for the treatment of congestive heart failure because it improves cardiac hemodynamics by afterload reduction and has a strong vasodilating effect on renal vascular beds.

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The clinical effect of nilvadipine, a new calcium antagonist, was in-vestigated in a single blind trial in 19 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holier electrocardiographic findings during observation periods and during two treatment periods when the drug was given in doses of 4mg twice a day or 4mg 3 times a day.
The frequency of anginal attacks and the consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with those in the observation period before treatment, but in the observation period after treatment tended to increase in comparison with those during the second treatment period.
The frequency and duration of ST-segment elevation and the maximum ST-segment elevation confirmed by Holter electrocardiography also improved significantly in both treatment periods, compared with those in the observation period before treatment. Our findings show that nilvadipine is effective for variant angina pectoris at doses of 4mg twice a day.

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To evaluate the incidence and severity of ventricular arrhythmias (VA) in a large group of patients who underwent corrective surgery for tetralogy of Fallot (TF) more than 4 years previously (mean age at surgery: 6 years 5 months), cardiac catheterization and cineangiography as well as 24 hour ambulatory Holter electrocardiography (HE) were performed in 45 patients.
Fifteen (33%) of the 45 patients had VA of Lown grade 2 or greater. Patients with VA (group I) were found to be significantly older at surgery than patients without VA (group II) (p<0.05). There were no significant differences in the ratio of postoperative right and left ventricular systolic pressures (RVSP/LVSP), and also right ventricular ejection fraction (RVEF) between the 2 groups.
As far as we know, none of our patients has suffered a sudden late death after repair of TF. Still, the overall incidence of VA was significantly high.

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In order to evaluate the role of calcium regulating hormones in the pathogenesis of mitral ring calcification, we have studied the serum levels of PTH and vitamin D metabolites in aged females both with and without mitral ring calcification (MRC).
In the patients with MRC (n=17), significantly lower levels of serum total protein (6.6±0.2 in the MRC group vs 7.1±0.1g/dl in the control group, mean±SEM), BUN (15.7±0.9 vs 18.3±0.9mg/dl), creatinine (0.7±0.02 vs 0.9±0.02mg/dl) and calcium (8.4±0.1 vs 9.2±0.1mg/ml) were observed as compared with those in the controls (n=32). Significantly higher PTH levels (0.57±0.07 vs 0.38±0.04ng/ml) were found in the MRC group. Levels of all three vitamin D metabolites in the MRC group were significantly lower than those in the control group (25-OHD; 11.2±1.4 vs 19.6±1.2ng/mMl, 24, 25 (OH)₂D; 0.7±0.1 vs 1.3±0.1ng/ml and 1, 25 (OH)₂D; 12.5±2.4 vs 43.0±3.5pg/ml). The correlation coefficient between PTH and 1, 25 (OH)₂D was -0.382 (n=49, p<0.01). Thus, the significantly higher PTH levels in the MRC group might result in hypovitaminosis D.
In conclusion, evidence of hypovitaminosis D in the patients with mitral ring calcification was demonstrated.

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Three patients with clinically proven myocarditis who later developed dilated cardiomyopathy (DCM)-like features were studied pathologically at necropsy and compared with 42 other cases with DCM.
The patients were an 18 year old female, a 20 year old male and a 28 year old male. They all had an upper respiratory tract infection as a prodromal symptom and then developed dyspnea on effort, electrocardiographic changes and cardiomegaly. In case 1, the antibody titers for Coxsackie B₂ virus were elevated. In cases 1 and 3, myocardial biopsies revealed a mononuclear cell infiltrate. All 3 died of congestive heart failure.
Histologically, layer-unit depletion of the myocardium (the myocardial damage and its sequelae (loss or minimal fibrosis) are restricted to certain layers), infiltration of mononuclear cells and moderate fibrosis were noted. In case 3, fibrosis and layer-unit depletion of the myocardium were mild. In our 42 DCM cases, the mean area of fibrosis was 40% in the fibrosis type, 15% in the nonfibrosis type and 30% in chronic myocarditis. In postmyocarditic cardiomegaly (PMC), the areas of fibrosis were 21.6%, 21.7% and 13.1% for the 3 cases. Mean cellularity indexes were 3.9% in PMC, 5.1% in the fibrosis type of DCM, 19.4% in the chronic myocarditis cases and 27% in the nonfibrosis type of DCM. With respect to fibrosis and interstitial cellularity, PMC most resembles the nonfibrosis type of DCM.

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The final number of antihypertensive drugs used in the long-term treatment of a given patient is not always predictable at the start of therapy. By reviewing clinical records, we retrospectively examined the relationship between pretreatment blood pressure and the final number of drugs administered in 282 patients with mild to moderate hypertension who had been treated for 5 years or more (average 9.7 years). After years of treatment approximately one third and one half of 137 patients with a pretreatment diastolic blood pressure of between 90 and 104mmHg were well controlled with combined therapy and monotherapy, respectively. The drugs had been withdrawn in the remaining 17% for 12 months or more. Lower pretreatment systolic blood pressure and lower pretreatment QRS voltage were signs favorable for withdrawal of the drugs. Combined therapy was required in more than half the patients with higher pretreatment diastolic blood pressure.

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Though the efficacies of procainamide and disopyramide in treating arrhythmias are well established, their precise mechanisms of antiarrhythmic action remain unclear. Arrhythmias which occur during acute myocardial ischemia can be explained partly on a metabolic basis. The accumulation of intermediates subsequent to impaired β-oxidation of free fatty acids has been suggested as a cause of serious arrhythmias. The purpose of this study was to investigate changes in free carnitine, long chain acyl carnitine and long chain acyl CoA concentrations in the ischemic canine heart following the administration of procainamide and disopyramide. The coronary artery was occluded for 40min and myocardial samples were prepared from both nonischemic and ischemic areas. Procainamide and disopyramide prevented the accumulation of long chain acyl carnitine and long chain acyl CoA in the ischemic myocardium. The results showed that procainamide and disopyramide had beneficial effects on fatty acid metabolism. It was suggested that one of the antiarrhythmic mechanisms of these drugs might be the prevention of the accumulation of fatty acyl derivatives in the isehemic myocardium.

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The effects of calcium (-)-N-[(S)-3(N-cyclohexylcarbonyl-D-alanyl)-thio]-2-methylpropion]-L-prolinate (MC-838, altiopril calcium), an in-hibitor of angiotensin converting enzyme, were investigated in 9 isolated atrial preparations and 7 intact anesthetized donor dogs. In 7 intact dogs, 1-10mg/Kg of MC-838 caused a decrease in systemic blood pres-sure, but no significant influence on heart rate was observed. At the same time, in isolated atria perfused with donor's blood, significant in-creases in developed tension and slight increases in sinus rate were observed with 3 and 10mg/Kg of MC-838. Intraarterial MC-838 at 10-300μg did not induce significant cardiac effects and MC-838 at 1-3mg caused an increase in developed tension and a slight increase in sinus rate. The positive inotropic and chronotropic effects were not blocked by adequate doses of propranolol, which significantly blocked norepinephrine-induced positive chronotropic and inotropic effects. It is concluded that a large amount of MC-838 has slight cardiotonic properties which are not medi-ated via a beta-adrenergic mechanism.

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The cardiovascular effects of a specific bradycardic agent, AQ-A 39, were investigated in intact donor dogs and isolated and cross-perfused dog heart preparations. Intravenous administration of AQ-A 39 (10-1000μg/kg) to the donor dog caused a dose-dependent heart rate de-crease in the donor dog and a decreased atrial rate in the isolated atrium perfused by the donor's blood. The arterial blood pressure of the donor dog and contractile force of the atrial preparation were unchanged or slightly decreased. The direct injection of AQ-A 39 (1-300μg) into the sinus node artery of the isolated atrium caused dose-dependent negative chronotropic and slight, transient positive inotropic responses. Alinidine and verapamil caused marked negative chronotropic and inotropic re-sponses. The negative chronotropic effect of AQ-A 39 was not modified by atropine. However, it was enhanced slightly but significantly by pro-pranolol, indicating that AQ-A 39-induced bradycardia was antagonized partly by beta-adrenoceptor function. These results confirmed that AQ-A 39 selectively reduced sinus rate by a direct action on the sinus node. Furthermore, the potency of the bradycardic action, compared with the decrease in contractility, was greater than for alinidine or verapamil. AQ-A 39 (300μg) tended to depress norepinephrine (NE)-induced positive chronotropic but not inotropic effects in isolated atria. By contrast, verapamil (3-10μg) significantly depressed the NE-induced positive iso-tropic but not the chronotropic effect, and propranolol (10μg) sup-pressed both cardiac effects of NE. These data suggest that the AQ-A 39-induced, selective attenuation of the NE-induced chronotropic effect is not due to either calcium channel blockade or beta-adrenoceptor an-tagonism.

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The effects of a novel piperazine derivative (INO 2628) on sinus node pacemaker activity and atrial contractile force were investigated in isolated, blood-perfused dog atrium. Injections of INO 2628 (0.03-100μmol) into the sinus node artery of the isolated atrium induced a dose-dependent decrease in sinus rate and an increase in contractile force. The positive inotropic effects at more than 10μmol were accompanied by a transient negative inotropism. Propranolol did not affect the positive inotropic response to INO 2628, but it significantly suppressed positive chronotropic and inotropic responses to norepinephrine. Atropine at a dose which completely blocked negative chronotropic and inotropic responses to carbachol, produced a slight but significant depression of INO 2628-induced negative chronotropic responses; inotropic responses were unaffected. These results suggest that INO 2628 induces noncholinergic negative chronotropic and nonadrenergic positive inotropic responses in isolated dog atria.

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A patient with familial hypertrophic cardiomyopathy with exertional near syncope is reported. Intra-right ventricular obstruction was demonstrated by hemodynamic studies during inspiration and the Valsalva maneuver with systemic hypotension. Improvement occurred following the administration of propranolol. It was suggested that syncope might be precipitated by hemodynamic changes such as a high output state and a depressed cardiac volume in relation to intra-right ventricular obstruction in patients with hypertrophic cardiomyopathy.

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There is no evidence in the literature that coronary artery spasm is induced by indocyanine green (ICG). In the present report, we describe 2 cases who developed chest pain with transient ST elevation on electrocardiograms after intravenous administration of ICG.

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A 13 year old boy had a wide QRS complex tachycardia. A discontinuity in the AV nodal functional curve was observed in the electrophysiologic study. The AV interval was prolonged in association with progressive ventricular preexcitation. At maximal preexcitation, the HV interval was -20msec and the QRS complex was identical to that seen during clinical tachycardia. No VA conduction was found and atrial premature beats did not affect the tachycardia. The His deflection was found at variable timing when tachycardia was induced. These findings confirmed that tachycardia originated within the AV node and was conducted to the ventricle over the Mahaim fiber. The short effective period of the Mahaim fiber had clinical significance since when atrial fibrillation developed, a rapid ventricular response was observed.

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