Protection by carbocromene and molsidomine against arrhythmias occurring during coronary artery occlusion and reperfusion in dogs.
We studied the effects of carbocromene (4 mg/kg plus 40 micrograms/kg/min i.v.) and molsidomine (0.1 mg/kg plus 2 micrograms/kg/min i.v.) on arrhythmias occurring during 90-min occlusion and 30-min reperfusion of the left anterior descending coronary artery in anesthetized dogs. Both drugs reduced the incidence of left ventricular (LV) premature depolarization during ligation (39% after carbocromene and 33% after molsidomine vs. 80% in controls; both p less than 0.05) and tachycardia (44% after carbocromene and 38% after molsidomine vs. 85% in controls; p less than 0.05). During reperfusion, the incidence of LV fibrillation was reduced in the carbocromene- (6 vs. 38% in controls; p less than 0.05) and molsidomine-treated dogs (10 vs. 38% in controls; p less than 0.05). The high incidence of ectopic activity and the ST segment elevation occurring after coronary ligation in control animals were prevented by both drugs. The hemodynamic deterioration after coronary occlusion, i.e., increase in blood pressure, LV systolic and end-diastolic pressures, LV dP/dtmax, and tachycardia observed in controls, was prevented by carbocromene. Molsidomine reduced blood pressure and LV pressure by 18 and 27% (p less than 0.05), respectively, during coronary occlusion. During reperfusion, no hemodynamic alterations occurred in the drug-treated animals. We conclude that carbocromene reduced the electrophysiologic consequences of acute ischemia by hemodynamic and anti-ischemic effects on heart metabolism. Molsidomine protected the jeopardized heart by a similar attenuation of hemodynamic derangement after coronary occlusion and perhaps by influencing prostanoid release from the ischemic myocardium.
V B
VB
Fiedler
B
B
Kettenbach
H
H
Göbel
R E
RE
Nitz
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D001157:Arterial Occlusive Diseases / Q000150:complications; D002866:Chromonar / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000503:physiopathology*; D003374:Coumarins / Q000627:therapeutic use*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D008297:Male; D008981:Molsidomine; D010069:Oxadiazoles / Q000627:therapeutic use*; D010477:Perfusion; D013558:Sydnones / Q000627:therapeutic use*; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*
D003374:Coumarins; D010069:Oxadiazoles; D013558:Sydnones; D014665:Vasodilator Agents; D008981:Molsidomine; D002866:Chromonar