denopamine and Cardiomyopathy--Dilated

Topics: Cardiomyopathy, Dilated; Chemotherapy, Adjuvant; Ethanolamines; Furosemide; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Pyridazines; Vasodilator Agents

Topics: Animals; Blood Pressure; Calcium; Cardiomegaly; Cardiomyopathy, Dilated; Ethanolamines; Heart Failure; Humans; Myocardial Contraction; Myocardium; Myosins; Receptors, Muscarinic

The possible chronotropic and arrhythmogenic effects of newly-developed oral inotropic agents were studied in 60 patients with idiopathic dilated cardiomyopathy (NYHA class II-IV). Changes in heart rates and the incidence of arrhythmias were evaluated using ambulatory electrocardiography. Denopamine 30 and 60 mg (beta 1 agonist), xamoterol 200 and 400 mg (beta 1 partial agonist) and OPC-8212 60, 90 and 120 mg (non-catecholamine) were sequentially administered for 10 +/- 2 months. Denopamine slightly increased heart rate throughout the day. Denopamine 60 mg caused excessive tachycardia in patients with atrial fibrillation, and could be used without digoxin. With xamoterol, maximum heart rate decreased during the daytime, while heart rate increased at night. Xamoterol was highly effective in patients with atrial fibrillation who not only had excessive tachycardia during exercise but marked bradycardia at night. Xamoterol increased the severity of heart failure in two patients who belonged to NYHA class IV, whose heart rates at rest had exceeded 100 beats/min. OPC-8212 did not affect heart rate, and was considered an ideal inotropic agent. None of these agents aggravated arrhythmias or caused sustained ventricular tachycardia. It was concluded that not only the severity of heart failure but the chronotropic and arrhythmogenic effects should be considered when choosing inotropic agents.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathy, Dilated; Cardiotonic Agents; Circadian Rhythm; Digitalis; Drug Evaluation; Electrocardiography, Ambulatory; Ethanolamines; Female; Heart Rate; Humans; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Propanolamines; Pyrazines; Quinolines; Xamoterol

To evaluate right ventricular (RV) function in severe left ventricular (LV) failure, we measured RV and LV ejection fractions (EF) in 18 patients with old myocardial infarction (OMI) and in 18 with dilated cardiomyopathy (DCM) using cardiac blood pool scintigraphy. In patients with OMI, RVEF was significantly greater in stage II LV failure than in stage III (functional class of the New York Heart Association, 47 +/- 8% and 28 +/- 12%, respectively: p less than 0.01), and this correlated well with exercise tolerance by bicycle ergometer and mean pulmonary artery pressure (r = 0.83 and r = -0.71, respectively). In patients with DCM, however, there was no correlation between RVEF and these indexes. After the oral administration of denopamine (beta 1 effector), both RVEF and LVEF increased in patients with OMI (35 +/- 13% to 45 +/- 12%, and 27 +/- 9% to 30 +/- 10%: p less than 0.01), but they did not change significantly in patients with DCM. These results indicate that RVEF in patients with OMI correlates well with subjective symptoms, exercise tolerance and RV afterload, but these correlations were not apparent in patients with DCM. We concluded that RV function in cases of severe LV failure has a different meaning between OMI and DCM.

Topics: Adult; Cardiomyopathy, Dilated; Cardiotonic Agents; Ethanolamines; Exercise Test; Heart Ventricles; Humans; Middle Aged; Myocardial Infarction; Radionuclide Angiography; Stroke Volume

In 18 patients with dilated cardiomyopathy (DCM), the effects of a new cardiotonic agent, TA-064, given in both consecutive and intermittent (3 days on, 11 days off) oral doses were studied for 3 months by echocardiography and endomyocardial biopsy. After 3 months of consecutive administration, 11 patients (61%) had improved symptomatically and the %FS increased (p less than 0.001) and LVDd decreased (p less than 0.05), but the other 7 patients had not improved. At the pretreatment state these 7 patients in whom TA-064 was not effective had smaller %FS (p less than 0.01) and larger LVDd (p less than 0.05) than the 11 patients in whom the drug was effective. The non-effective group also had more severe myocardial fibrosis (p less than 0.05) and cellular hypertrophy (p less than 0.01) than the effective group. After 3 months of intermittent administration in 10 patients in whom consecutive administration had been proved effective, 7 patients sustained symptomatic improvement and increased %FS (p less than 0.01), but the other 3 patients did not sustain the improvement. The latter group had smaller %FS, larger LVDd and more severe myocardial fibrosis than the former group at the pretreatment state. These results indicate that the effects of TA-064 are dependent on the severity of basal cardiac function and myocardial damage, and that in patients with milder DCM, the effects can be sustained by intermittent administration.

Topics: Adult; Aged; Cardiomyopathy, Dilated; Cardiotonic Agents; Diastole; Ethanolamines; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardium

Topics: Administration, Oral; Adult; Aged; Cardiomyopathy, Dilated; Cardiotonic Agents; Dose-Response Relationship, Drug; Ethanolamines; Female; Hemodynamics; Humans; Male; Middle Aged

According to investigations conducted in Japan, TA-064 is a new cardiotonic agent, which is also effective orally. We analyzed computer-assisted alterations of pressure-volume relations serially and of MVO2 online (Bretschneider) during TA-064 influence in 16 patients with congestive cardiomyopathy: LV-function of 7 patients was only moderately decreased (group A) and in 9 patients massively (group B).. 1) TA-064, 8 micrograms/kg/min, i.v. had positive inotropic effects in both groups and induced mean maximal delta% changes at about the 5th minute of infusion as follows: LVSWI + 65% and 47%; DP/DTmax + 61% and 59%; LV-efficiency + 62% and 53%; MVO2 + 31% and + 11% (p less than 0.05). 2) TA-064, 20 mg p.o. induced serum levels (A: 23.8 +/- 12 and B: 26.4 +/- 20 ng/ml) corresponding to the effects with the dosages 1-2 micrograms/kg/min, i.v. (p greater than 0.05), thus implying that significant changes in LV-function require higher p.o. dosages. 3) TA-064 i.v. on the 6th day of exposure to the medication produced less LV-function improvement than on day 1 (p greater than 0.05).. In both groups A and B TA-064 improves LV-function primarily via increased contractility, without toxic side effects. For a more complex definition of the efficiency and mechanism of cardiotonic agents, the validity and importance of using on-line MVO2 assessment and analysis of serial pressure-volume relations is stressed.

Topics: Adult; Blood Pressure; Blood Volume; Cardiac Output; Cardiomyopathy, Dilated; Cardiotonic Agents; Computers; Dose-Response Relationship, Drug; Ethanolamines; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Myocardium; Online Systems; Oxygen Consumption