Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat.

Abstract

The electrophysiologic changes associated with dysrhythmias induced by coronary occlusion and by subsequent reperfusion were characterized with six complimentary approaches in chloralose-anesthetized cats (n = 57) with proximal occlusion of the left anterior descending (LAD) coronary artery. Occlusion led to reproducible ventricular dysrhythmia which abated in 35 minutes. The electrophysiologic effects of reperfusion initiated at this time could be studied. Simultaneous bipolar electrograms (epi-, myo- and endocardial) from ischemic and normal zones were analyzed by computer. Before the onset of the dysrhythmia induced by occlusion, conduction was markedly slowed, with dV/dt decreasing to 34% +/- 6% of control and conduction time (endo- to epicardial activation) prolonged to 328 +/- 77% of control. However, these values returned toward normal with reperfusion, even though it also consistently induced dysrhythmia. The idioventricular escape rate (determined by intense vagal stimulation) was 62 +/- 6 beats/min during the dysrhythmia induced by occlusion (equal to control), but increased during the reperfusion dysrhythmia to 188 +/- 12 beats/min. The occlusion dysrhythmia was exacerbated, but the reperfusion dysrhythmia was suppressed by rapid atrial pacing. The refractory period progressively shortened after occlusion and remained decreased during early reperfusion. Thus, increased conduction time through myocardial and epicardial regions, asynchronous depolarization and shortening of the refractory period accompanied dysrhythmia induced by occlusion. In contrast, the dysrhythmia induced by reperfusion was characterized by normal conduction time, through myocardial regions with continued significant epicardial delay, overdrive suppression, synchronous depolarization and a high idioventricular rate.

Electrophysiology of coronary reperfusion. A mechanism for reperfusion arrhythmias.

“…Since reentry is dependent ) upon slowed conduction, and reperfusion rapidly reverses the ischemic induced conduction delav, these observations would initially appear to negate a reentrant mechanism for reperfusion arrhythmias. Indeed, the similar finding of a rapid improvement in conduction after 35 minutes of coronary occlusion was taken as strong evidence against a reentrant mechanism in the feline model of reperfusion arrhythmias (9). However, although conduction improves with reperfusion, in those areas of the heart rendered unresponsive by ischemia, the conduction improvement Ventricular automaticity was assessed in five dogs during reperfusion after complete atrioventricular (AV) block was produced by injecting formalin into the AV node according to the method described bv Loeb et a 1 ( 71).…”

Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

“…[17][18][19][20] Other studies, using either coronary artery ligation or reperfusion models, have also suggested that a large and variable number of animals do not develop ventricular fibrillation, even without prior antiarrhythmic therapy (approximately 60% and 30%, respectively).2 29 Previous studies in this laboratory, however, indicate that the risk for developing ventricular fibrillation on reperfusion might be predicted for individual animals based on the incidence, time course and severity of arrhythmias occurring during the antecedent period of acute coronary artery ligation. 30' 31 This was predicated on the observation that different animals subjected to acute one-stage ligation of the proximal left anterior descending coronary artery developed either immediate (occurring 2-12 minutes after ligation), delayed (occurring 14-30 minutes after ligation), both types or no ventricular arrhythmias at all;32' 33 and that the risk for ventricular fibrillation during the subsequent period of coronary artery reperfusion correlated closely with the occurrence of these ligation arrhythmias.…”

Electrophysiological basis for the antiarrhythmic action and positive inotropy of HA‐7, a furoquinoline alkaloid derivative, in rat heart

“…It is well known that transient coronary artery occlusion can lead to malignant ventricular arrhythmia during ischaemia and reperfusion (Penkoske et al, 1978;Janse & Kle ber, 1981;Ferrier et al, 1985). The mechanism(s) underlying the genesis of these lethal arrhythmias (ventricular tachycardia and ventricular ®brillation) are complex but may include the reentry and the oscillatory afterpotentials (Manning & Hearse, 1984;Ferrier et al, 1985;Pogwizd & Corr, 1987).…”