The hemodynamic background associated with the occurrence of paroxysmal atrial fibrillation and flutters (PAF), in patient with acute myocardial infarction (AMI) were evaluated. Sixty-seven of 381 consecutive AMI patients (17.6%) were noted to have PAF in the acute phase of infarction. These 67 patients with PAF (group 1) were compared with 60 randomly selected patients without PAF (group 2). The hospital mortality rate was 25.4% in group 1, and 11.7% in group 2 (p<0.01). The hemodynamic variables measured before the onset of PAF in group 1, showed significantly more unfavorable values than those in group 2, which were measured at the time of admission. The 67 patients in group 1 were divided into 50 patients who survived (group S) and 17 patients who died in the hospital (group D). The hemodynamic status in group D demonstrated significantly larger deterioration before the onset of PAF than in group S. Hemodynamic variables were compared before and during PAF in groups D and S, cardiac index (CI) decreased significantly, and stroke index (SI) decreased by 46% in group D, with no decrease in CI and less decrease in SI (28. P<0.05) in group S. In conclusion, not only the occurrence of PAF, but the prognosis of patients with PAF is dependent on the severity of hemodynamic disturbance imposed by AMI. Atrial contribution to ventricular filling has great importance in the maintenance of the cardiac output in this patient population.

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In prospective study, the β₁-Partial agonist xamoterol (200 mg daily) was given to 26 patients with idiopathic dilated cardiomyopathy (DCM) in addition to conventional therapy with digitalis, diuretics and vasodilators. The patients were followed for 35 ± 15 months (6-53 months). Cardiothoracic ratio (CTR), left ventricular end-diastolic dimension (LVDD) and exercise heart rate decreased, and exercise duration, fractional shortening (FS) and ejection fraction (EF) increased after xamoterol therapy. Twenty-one patients survived and one patient dropped out at 7 months. Twelve of the 20 patients improved their NYHA functional class. Blood norepinephrine concentration (NE), LVDD, FS, EF and pulmonary capillary wedge pressure (PCWP) after xamoterol were significantly better in survivors than in non-survivors. Survival rate at 3 years was 83%. The results suggest that adjunctive xamoterol therapy in DCM has a beneficial effect on hemodynamics and symptoms. Prognosis will be satisfactory if improvement in parameters such as NE, LVDD, FS, EF and PCWP is seen during xamoterol therapy.

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To evaluate the role of regional hemodynamics in the anti-hypertensive effect of mepirodipine, a new dihydropyridine-derivative calcium antagonist, we measured systemic, renal, hepatic, and forearm hemodynamics in 10 patients with essential hypertension treated with mepirodipine (15 mg/day) for 4 weeks. After the administration of mepirodipine, a significant decline in mean blood pressure (-13.8±2.3%, p<0.01) accompanied by a decrease in systemic vascular resistance (-21.1 ± 2.6%, p<0.01) was observed. Although forearm vascular resistance did not change significantly, both renal (-19.2±6.7%, p<0.01) and hepatic vascular resistance (-17.6±3.8%, p<0.01) decreased considerably. The decrements of mean blood pressure with mepirodipine did not correlate with those of hepatic or forearm vascular resistance but correlated positively with those of renal vascular resistance (r=0.699, p<0.05). Moreover, the increment of renal blood flow with mepirodipine was negatively correlated with the pretreatment level of renal blood flow (r=-0.670, p<0.05); renal blood flow increased to a greater extent in patients with lower pretreatment renal blood flow. These findings suggest that the oral administration of mepirodipine in patients with essential hypertension can produce selective vasodilation in the renal vasculature, which may play an important role in the relatively long-term antihypertensive effect of this drug.

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A 51-year-old female who was hospitalized for evaluation of frequent episodes of hypotension, died unexpectedly. At autopsy, there were many fine, white granular deposits in the myocardium, which were more prominent in the subepicardium of the left ventricle than in the subendocardium. Pathologic calcification is sometimes seen in chronic hemodialysis patients and in some organs the sites of calcium deposition are quite specific. There have been few reports concerning the pattern of calcium deposition in the myocardium and, to our knowlege, the reason for this characteristic distribution is unknown. However it may relate to hydrogen ion concentration in the myocardium.

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The clinical efficacy of enalapril was investigated in 21 patients with severe heart failure. For each subject, the following parameters were compared before and one month after enalapril maintenance treatment. NYHA functional class, Kill's class, cardiothoracic ratio (CTR), left ventricular (LV) function estimated by echocardiography and gated equilibrium radionuclide angiography, Holter ECG recordings, serum digoxin concentration (SDC), plasma remin activity, plasma aldosterone concentration, plasma norepinephrine concentration (PNE), etc. Short- and long-term hemodynamic responses to enalapril were also studied, with simultaneous measurement of enalapril concentation by radioimmunoassay. After maintenance therapy, patients showed a significant improvement as judged by NYHA functional class, Killip's class, and CTR. The LV fractional shortening and the ejection fraction significantly increased. The frequency of ventricular tachycardia showed a significant tendency to de-crease after the therapy. The SDCs Were unchanged, which indicates no pharmacokinetic drug interaction between digoxin and enalapril. Hemodynamic assessment showed a reduction in systemic vascular resistance, a reduction in mean blood pressure, and an increase in the cardiac index. No major side effects were observed during the study period. According to a multivariate analysis, the coefficient of determination of PNE was the highest for the final global improvement rating. This may reflect the neurohormonal improvement of cangestive heart failure by enalapril therapy. In conclusion, enalapril is recommended for treating patients with severe CHF.

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In recent years, captopril has attracted considerable clinical attention as an agent for use in treating heart failure. We administered 15 mg/kg of captopril or 1.5 mg/kg of enalapril to 5-week-old J-2-N cardiomyopathic hamsters for 10 or 15 weeks, and investigated the roles of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the onset and progress of cardiomyopathy. In the untreated group, serum creatine kinase levels increased in accordance with the progression of cardiomyopathy, but this increase was markedly inhibited by the administration of captopril. The rise in serum aldolase levels was similarly inhibited. Serum malondialdehyde levels were significantly reduced by the administration of captopril. ECG findings and the ventricular myosin isoenzyme pattern were also markedly improved by captopril. The improvement in all these parameters was less with enalapril. These differences between captopril and enalapril suggest that increases in tissue bradykinin and vasodilatory prostaglandins may play an important role in the beneficial effects of captopril.

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Twenty-three patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses compared with those of 26 patients untreated with β-blocking agents (non β group). Of the 23 patients treated with metoprolol, 20 (β group) were treated for 6 months or longer, while the remaining 3 patients were intolerant of the drug and suffered aggravation of heart failure. In the β group, 2 deaths occurred, while of the remaining 18 patients 4 were considered clinically improved in NYHA class 6 or 12 months later, and none suffered clinical deterioration during the follow-up period. In the non-β group, clinical improvement was found in 2 patients and deterioration of functional class in 10. Heart rate and pressure rate product were significantly decreased by I month after the treatment with metoprolol. At that time, blood pressures, systolic and diastolic left ventricular dimensions, indices of systolic function (%FS, mVcf) and exercise capacity had not changed, while cardiac output was decreased and systemic peripheral vascular resistance was significantly increased. In the β group, significant inprovements in left ventricular dimensions, systolic function and exercise tolerance were delayed and observed within 3 to 6 months during the follow-up period, while no such improvements occurred in patients of the non- β group. During the follow-up period, 2 patients of the β group and 10 patients of the non-β group died. The survival curve for patients of the β group, prepared using the Kaplan Meier's Method, was better than that for patients of the non-β group. Metoprolol was therefore found to be useful for treatment of DCM.

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Tachycardia may play a key role in the progression of heart failure probably through Ca²⁺ overload. In the present study, to test whether microtubules, Ca²⁺-sensitive cytoskeletons, are disrupted by rapid contractions and whether the beta-adrenoceptor antagonist, propranolol could attenuate the disruption of microtubules, cultured neonatal rat cardiomyocytes with various contraction rates were studied. The microtubules were stained by immunohistochemical technique and the extent of microtubule disruption was quantified by disruption scores (grade 0-intact; grade 3-severe disruption). In 97% of the non-contracting cells, intact microtubules (grade 0) were observed, whereas in the cells that contract at the rate of 100-120/min, intact microtubules were observed only in 25% of the cells. The disruption scores were significantly correlated with con-traction rates of the cells. Treatment with propranolol (10^-6M) decreased the extent of microtubule disruption associated with a decrease in the contraction rate. However, this treatment did not alter the relationship between the con-traction rate and the disruption score of microtubules. These results indicate that rapid contractions may induce disruption of microtubules which can be attenuated by beta-blocker mainly by its negative chronotropic effect. This may be one of the underlying mechanisms of the long-term effect of beta-blockers for chronic heart failure.

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The usefulness and limitations of antiarrhythmic drugs in ventricular tachycardias (VT) associated with congestive heart failure remain uncertain. The purpose of this study is to evaluate the proarrhythmic effects of antiarrhythmic drugs in patients with refractory VT associated with left ventricular dysfunction using electrophysiologic study (EPS). Twenty-four patients with left ventricular dysfunction, defined by left ventricular ejection fraction (LVEF) lower than 40% using left ventriculography, were studied. The average LVEF was 29.5%. As for underlying heart disease, 14 had old myocardial infarction, 8 cases had dilated cardiomyopathy and 2 had aortic regurgitation. As a control to this group, 23 cases with underlying heart disease and LVEF higher than 40%, and 27 cases with no obvious heart disease were studied. We considered a drug to have proarrhythmic effects if 1) it de-creased by one the number of stimuli needed to induce VT, 2) induced non-sustained VT in the control study which changed to induced sustained VT, 3) the sustained VT or ventricular fibrillation was newly induced, or 4) the induced sustained VT which was stopped by pacing in the control study changed to induced VT which could not be terminated by pacing and required DC shock. Proarrhythmic effects were recognized in 17 of 24 cases with left ventricular dysfunction. Of the 67 drug trials, proarrythmic effects were seen in 26. Proarrhythmias were observed in 9 of 23 cases (39.1%) with organic heart disease associated with LVEF higher than 40%. In 12 of 69 drug trials (17.4%) proarrhythmias were observed. Of 27 cases with no obvious heart disease 10 cases (37%) had proarrhythmias. In 14 of 130 drug trials (10.8%), proarrhythmias were recognized. In conclusion, the incidence of ventricular arrhythmias on EPS in cases with low LVEF was 70.8%, and 33.8% in drug trial, higher than in cases with organic heart disease and LVEF higher than 40%. Although the relation to spontaneous occurrence is not always clear, the effects of antiarrhythmic drugs therapy on ventricular arrhythmias in patients with congestive heart failure needs careful consideration and should be an interesting topic for future research.

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Antiarrhythmic effects of beta-blockade (BB) in patients with dilated cardiomyopathy were compared with those of various antiarrhythmic agents using ambulatory Holter monitoring. The BB therapy effectively suppressed ventricular extrasystoles (VEs) in 85% of patients, as evidenced by improvement in Lown's grade or a reduction in the number of the highest grade Ves<50%. In contrast, conventional antiarrhythmic agents, except flecainaid and amiodarone, were poorly effective in suppressing VEs. BB therapy gradually increased left ventricular fractional shortening (16±6% to 22±12%) and improved 12-month survival rates as compared with those receiving conventional therapy (93 vs 69%). This antiarrhythmic potency seemed to be an additional therapeutic efficacy of BB in the management of patients with dilated cardiomyopathy, which frequently associated with serious VEs.

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To evaluate the therapeutic efficacy of l-carnitine in heart failure, the myocardial carnitine levels and the therapeutic efficacy of l-carnitine were studied in cardiomyopathic BIO 14.6 hamsters and in patients with chronic congestive heart failure and ischemic heart disease. BIO 14.6 hamsters and patients with heart failure were found to have reduced myocardial free carnitine levels (BIO 14.6 vs FI, 287±26.0 vs 384.8±83.8 nmol/g wet weight, p<0.05; patients with heart failure vs without heart failure, 412±142 vs 769±267 nmol/g p<0.01). On the other hand, long-chain acylcarnitine level was significantly higher in the patients with heart failure (532±169 vs 31772 nmol/g, p<0.01). Significant myocardial damage in BIO 14.6 hamsters was prevented by the intraperitoneal administration of l-carnitine in the early stage of cardiomyopathy. Similarly, oral administration of l-carnitine for 12 weeks significantly irnproved the exercise tolerance of patients with effort angina. In 9 patients with chronic congestive heart failure, 5 patients (55%) moved to a lower NYHA class and the over-all condition was improved in 6 patients (66%) after treatment with l-carnitine. L-carnitine is capable of reversing the inhibition of adenine nucleotide translocase and thus can restore the fatty acid oxidation mechanism which constitutes the main energy source for the myocardium. Therefore, these results indicate that l-carnitine is a useful therapeutic agent for the treatment of congestive heart failure in combination with traditional pharmacological therapy.

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We compared the effect of oral administration of taurine (3g/day) and coenzyme Q₁₀ (CoQ_<>) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echo-cardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ₁0-treated group.

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Sixteen patients with acute profound heart failure (HF) have been treated with the left ventricular assist device (LVAD), nine of them were successfully weaned from LVAD, and three of them were discharged and survived longer. Decompression of the left ventricle (LV) at the beginning will prevent overex-tension of impaired myocardium and accelerate scar formation. Gradual in-crease of LV work will promote the compensation ability of the residual myocardium. We found that continuous LVAD assistance can give time for the impaired heart to recover while maintaining normal circulation. For patients with profound HF which is beyond the limit of intra-aortic balloon pumping's (IABP) capability, LVAD is a more powerful and effective means. Although the heart recovered, many patients later died of multiple organ failure (MOF) which was probably caused by prolonged ischemia before LVAD application. For completely successful recovery from profound HF, diagnosis and deciding to use LVAD should not be delayed. It should be applied before major organs including the heart itself suffer irreversible damage. We have established a systematic therapeutic concept of treating acute HF patients using assisted circulation including LVAD.

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During the last 3 years, left or bi-ventricular support using a centrifugal pump as a ventricular assistance device was performed in 10 patients after open heart surgery. The basic lesions were coronary heart disease in 8 and valvular disease in 2 patients. Bypass support ranged in time from 33 to 240 h (average 114 h), and 3 patients received biventricular support. Six patients have survived in this group. Other supportive methods, in the form of emergency or elective use of portable cardiopulmonary bypass support, were used in 8 patients; 4 with cardiogenic shock and 4 for supported percutaneous coronary angioplasty. These assisted circulations appear to be useful and promising in the management of the critical cardiac patient.

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