Pharmacologic modifications of reperfusion arrhythmias in the dog in vivo: possible relation to limitation of the extent of infarction.
To study the effects of pharmacologic interventions on reperfusion-induced arrhythmias, open chest anesthetized dogs were subjected to occlusion of a coronary artery for 3 hours followed by reperfusion for 3 hours. Electrocardiograms were recorded with a two-channel monitor with the subsequent recordings submitted to computer-assisted analysis. The extent of myocardial infarction was measured by staining with triphenyl tetrazolium chloride. Mexiletine (12 mg/kg) and verapamil (0.9 mg/kg) were given, starting at 120 min of coronary occlusion and continued until the end of experiments. Dibunol (60 mg/kg) was administered at 120 min of ischemia. Dibunol and dibunol together with verapamil reduced the extent of infarction (to 62 +/- 6% and 53 +/- 4% of the zone at risk, respectively; compared to 77 +/- 3% of the zone at risk in the control group, P less than 0.05) while verapamil alone and mexiletine did not. There were 5 fatal episodes of ventricular fibrillations in 23 dogs, together with other malignant arrhythmias when occlusion was released in the control group. Mexiletine and verapamil prevented these episodes of ventricular fibrillation during reperfusion while dibunol, and dibunol together with verapamil, did not. Apart from fibrillations, mexiletine eliminated ventricular tachycardias, in contrast to the other drugs, which did not. Mexiletine and verapamil alone prevented ventricular premature beats while dibunol, and dibunol with verapamil, exacerbated their generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Conorev
E A
EA
Institute of Experimental Cardiology, USSR Cardiology Research Centre, Moscow.
Rudnev
D V
DV
Conorev
L A
LA
Polumiskov
V Y
VY
Golikov
A P
AP
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy*; D002084:Butylated Hydroxytoluene / Q000627:therapeutic use; D004285:Dogs; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D008801:Mexiletine / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy; D014700:Verapamil / Q000627:therapeutic use
D002084:Butylated Hydroxytoluene; D008801:Mexiletine; D014700:Verapamil