Anesthetized rabbit as a model for ischemia- and reperfusion-induced arrhythmias: effects of quinidine and bretylium.
Experiments were performed to assess the feasibility of using anesthetized rabbits for the study of ischemia- and reperfusion-induced arrhythmias. Initial studies indicated that occlusion of the left anterior descending coronary artery produced ectopic activity in only one out of eight rabbits. All rabbits subject to occlusion of the left circumflex artery below where it emerges from under the left atrial appendage had ECG changes (ST-segment elevation, Lead II), 80% had arrhythmias, and 50% died in ventricular fibrillation during the first 20 min of coronary artery occlusion. Subsequent reperfusion in the survivors produced further arrhythmias in the majority of rabbits, and one fibrillated. Although a high incidence of ectopic activity was also observed in rabbits subject to occlusion of the left circumflex artery close to its origin, or both the left anterior descending and circumflex arteries, this was accompanied by marked reductions in arterial blood pressure. Thus, occlusion of the left circumflex artery at the lower site was chosen for all further studies. Quinidine hydrochloride 10 mg kg-1 (n = 10) or bretylium tosylate 20 mg kg-1 (n = 10) administered 15 min prior to coronary artery occlusion reduced the incidence of ischemia-induced ventricular fibrillation to 10% compared with 60% in controls (n = 15). Although bretylium reduced arterial blood pressure and heart rate, neither drug altered the hemodynamic consequences of coronary artery occlusion (e.g., increased left ventricular end diastolic pressure). Bretylium at doses of 5 and 20 mg kg-1, but not quinidine, reduced the ST-segment elevation that developed during the ischemic period. The ability to detect the antifibrillatory activity of quinidine and bretylium suggests that the anesthetized rabbit may provide a useful alternative or additional model for the study of arrhythmias induced by acute myocardial ischemia.
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
S J
SJ
Coker
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology*; D001949:Bretylium Compounds / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy; D003331:Coronary Vessels; D004195:Disease Models, Animal; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D011802:Quinidine / Q000627:therapeutic use*; D011817:Rabbits
D001949:Bretylium Compounds; D011802:Quinidine; C045166:bretylium