Brief periods of myocardial ischemia followed by reperfusion: a model in the dog of sudden cardiac death in humans.

Most experimental interest has focused on the electrophysiologic mechanisms which may underlie sudden death. The purpose of the present study was to develop a model in the dog where ischemia would produce not just ventricular fibrillation but also histologic abnormalities similar to those previously reported in sudden death in humans. First, the collateral blood flow to a portion of the ventricle was surgically abolished and then the arterial blood supply to this region was interrupted for 15 minutes after which nutrient flow was restored for 30 minutes. If the animal survived, this cycle was repeated up to seven times. Thirty-six animals were studied: 15 controls (Group A) survived an average of 1.75 +/- 0.8 cycles (mean +/- SD); 11 others (Group B) received a loading dose of sodium verapamil and survived 3.7 +/- 1.8 cycles while 10 (Group C) received a continuous infusion as well as the loading dose of sodium verapamil and survived 4.4 +/- 2.6 cycles--the difference between each group being significant (p less than 0.05). Four animals in Group C survived all 7 cycles; out of the other 32, 27 fibrillated just after reperfusion and the rest during ischemia. Histological examination revealed small foci of contraction band necrosis widely interspersed amongst large areas of morphologically normal tissue. The beneficial effect of verapamil and the histologic findings suggest cellular calcium overload may be important in the genesis of the fatal arrhythmias produced by reperfusion.