denopamine and Arrhythmias--Cardiac

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

We studied the arrhythmogenic activity of denopamine, in relation to its positive inotropic action, in dogs and compared it with those of catecholamines. The positive inotropic activities of the compounds as expressed in terms of the ED100 (microgram/kg, i.v.), that increased LV dp/dt max of anesthetized dogs by 100% of the control were 8.0 for denopamine, 0.27 for norepinephrine, 0.03 for isoproterenol, 3.8 for dobutamine and 16 for dopamine. On the other hand, the doses of these drugs at which the "non-sinus/total rate" increased significantly (about 30% of total beats, microgram/kg, i.v.) were more than 1000 for denopamine, 1.0 for norepinephrine and isoproterenol, and 300 for dobutamine and dopamine in coronary ligated dogs. The ratios of these doses to the ED100 are more than 126 for denopamine, 80 for dobutamine, 33 for isoproterenol, 19 for dopamine and 3.8 for norepinephrine. Arrhythmogenic activity of denopamine was also weaker than those of dobutamine and dopamine in halothane anesthetized dogs. The arrhythmogenic activity of dobutamine was weak as reported, but that of denopamine was the weakest among the drugs tested.

Topics: Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular System; Catecholamines; Dobutamine; Dogs; Ethanolamines; Halothane; Hemodynamics; Isoproterenol