Possible mechanisms of ventricular arrhythmias elicited by ischemia followed by reperfusion. Studies on isolated canine ventricular tissues.

The purpose of this study was to develop an isolated tissue model in which arrhythmic activity could be generated in response to conditions encountered in ischemia followed by reperfusion, and in which intracellular recordings could be used to identify and study arrhythmogenic mechanisms. Isolated canine Purkinje fiber-papillary muscle preparations were superfused with modified Tyrode's solutions. Tissues were exposed to conditions observed in ischemia (hypoxia, acidosis, elevated lactate, zero substrate for 40 minutes). Superfusion with Tyrode's solution of "normal" composition was then reinstituted. Transmembrane recordings from Purkinje and muscle tissues were made, using standard microelectrode techniques. Ischemic conditions caused loss of membrane potential, shortened action potentials, depressed excitability, and progressive bidirectional conduction block between muscle and Purkinje tissues. Spontaneous activity, probably reentrant in origin, was observed. Return to nonischemic conditions resulted in a multiphasic sequence of responses in Purkinje fibers: prompt hyperpolarization, progressive depolarization to unresponsiveness, and final repolarization to control. The depolarization phase was accompanied by oscillatory afterpotentials which initiated extrasystoles. Final repolarization included a phase of automaticity at low membrane potentials, during which Purkinje tissue functioned as a parasystolic focus. Elevation of potassium concentration to 10 mM during the ischemic period did not alter the sequence of electrophysiological events during ischemic conditions or upon reperfusion. This study demonstrates that ischemia followed by reperfusion elicits an orderly sequence of electrophysiological events which may constitute important mechanisms of arrhythmia in vivo.