Brief, intermediate and prolonged ischemia in the isolated crystalloid perfused rat heart: relationship between susceptibility to arrhythmias and degree of ultrastructural injury.

Isolated Langendorff-perfused rat hearts were used to assess susceptibility to reperfusion-induced arrhythmias after different durations of ischemia in relationship to structurally related impairment of heart function, and to examine whether phase two ischemia-induced arrhythmias occur in crystalloid perfused hearts. This was achieved by subjecting the hearts to 5 min reperfusion following either sustained (240 min), intermediate (30 min), or brief (10 min) regional ischemia. Sustained ischemia induced little arrhythmogenesis upon reperfusion (no ventricular fibrillation) and impairment of recovery of coronary flow (approximately 64% of uninvolved zone flow). Electron microscopic investigation of the ischemic region revealed severe degenerative damage of the ultrastructure of cardiac myocytes and capillary endothelial cells. In contrast, reperfusion following brief ischemia caused all hearts to develop ventricular fibrillation (VF), accompanied by a persisting hyperemia throughout the course of reperfusion (flow 149 +/- 33% of that in the uninvolved zone after 1 min of reperfusion). In this group, myocardial ultrastructure exhibited negligible i.e., almost complete reversal of injury, upon reperfusion. Intermediate (30 min) ischemia led to a high incidence of reperfusion arrhythmias (92% of hearts developing VF) and modest hyperemia (flow 111 +/- 22% of that in the uninvolved zone after 1 min of reperfusion). Moderate ultrastructural alterations and their further deterioration upon reperfusion were observed in some but not all hearts in this group. During ischemia, phase 1 arrhythmias were common (57% of hearts developed VF during the first 30 min). However, phase 2 arrhythmias were absent during 120-240 min ischemia in these isolated hearts. In conclusion sustained ischemia in the rat heart renders myocardium unviable with a consequent loss of susceptibility to reperfusion arrhythmias. Phase 2 ischemia-induced arrhythmias do not occur in this model, implicating an intact autonomic nervous system and/or circulating factors from blood (e.g., neutrophils) in phase 2 arrhythmogenesis.