Reperfusion-induced arrhythmias are critically dependent upon occluded zone size: Relevance to the mechanism of arrhythmogenesis

Abstract

The relationship between reperfusion-induced arrhythmias and the size of the occluded zone was examined. The isolated perfuse rat heart was used because its negligible collateral flow maximizes susceptibility to arrhythmias and reduces variability. Ischemia lasting 10 min was followed by 10 min of reperfusion. A constant-pressure perfusion system (which precludes coronary steal) permitted measurement of the rapidity of restoration of coronary flow. Mean occluded zone sizes of 0, 7.2 ± 1.1, 19.5 ± 1.5, 45.8 ± 1.7, 30.1 ± 4, and 100% of the total ventricular weight were obtained by sham ligation, distal, medial and proximal ligation of the left main coronary artery, right arterial ligation and the induction of global ischemia, respectively. Occluded zone size correlated positively ( r = 0.86, P < 0.001) with a linearly-additive arrhythmia score irrespective of the site of ischemia (left versus right ventricle). In globally ischemic hearts, ventricular fibrillation (VF) depended upon ventricular beating rate during ischemia, occurring only if the rate exceeded 150 beats/min. If this factor were taken into consideration, VF incidence exhibited a sigmoidal relationship with occluded zone size. During the first min of reperfusion, the rapidity of restoration of coronary flow was inversely related to occluded zone size ( P < 0.001) and had a small but significant effect on the severity of arrhythmias; slow recovery of flow increased susceptibility. We conclude that when reperfusion is elicited at the moment of peak susceptibility to arrhythmias, VF incidence is determined principally by occluded zone size. Heart rate during ischemia becomes relevant at rates less than 150 beats/min, when a protective effect is seen. Since VF incidence was 100% in hearts reperfused after global ischemia, an interface between non-ischemic tissue and reperfused tissue is therefore unnecessary for arrhythmogenesis during reperfusion, and flow of injury current between non-ischemic and reperfused tissue can be ruled out as a mechanism of arrhythmogenesis. The initiation of reperfusion-induced arrhythmias must therefore take place within the reperfused tissue.