Effects of the Na+ antagonist cibenzoline on left ventricular function of postischemic hearts.
The negative inotropic effect of antiarrhythmic drugs is a major drawback in antiarrhythmic drug therapy, especially in patients with reduced contractile function of the left ventricle. The circulatory and myocardial effects of the new class I antiarrhythmic drug (a Na+ antagonist), cibenzoline (2 mg/kg i.v.), were investigated in 47 open-chest rats with normal and postischemic myocardium (3 x 4 minutes of global ischemia). Hemodynamic measurements in the intact circulation and isovolumic registrations (peak isovolumic left ventricular systolic pressure and peak isovolumic dP/dtmax) were compared to saline controls. In rats with postischemic myocardium, cibenzoline caused a significant (p < 0.001) decrease in the cardiac output for 38%, in the dP/dtmax for 30%, and in the peak isovolumic dP/dtmax for 19% at the end of infusion (compared to the control). The heart rate was reduced by 22% (p < 0.001), the mean aortic pressure by 22% (p < 0.001), and the calculated systemic resistance by 20% (p < 0.001). In contrast to the results with postischemic myocardium, no important changes in the hemodynamics were detectable after an identical dose in normal animals without left ventricular dysfunction. The results indicate that standard doses of the Na+ antagonist cibenzoline may induce significant cardiodeperessant effects on postischemic left ventricles with reduced function.
Hoffmeister
H M
HM
Abt. III, Eberhard-Karls-Universität, Tübingen, Germany.
Beyer
M E
ME
Seipel
L
L
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D012964:Sodium; C032151:cifenline