The effects of ischemia on metabolism and reperfusion arrhythmias

In attempts to determine the mechanism(s) underlying reflow rhythm disturbances, we have studied the relationship between extent of coronary flow impairment and incidence of reperfusion arrhythmias. In isolated guinea pig hearts perfused with pyruvate (10 mmol/l) and glucose (0.5 mmol/l), coronary flow was reduced to different extents (18, 11, 6, 1, and 0.5%). Following 10 minutes of ischemia, reflow arrhythmias were quantitated with computer-aided statistical determination of rate-independent variations in beat intervals. The results (19 +/- 1, 13 +/- 5, 22 +/- 4, 8 +/- 3 and 6 +/- 1, n = 6, Rhythm Disturbance Units respectively) revealed that rhythm disturbances were more serious after less severe ischemia than after more severe ischemia. To investigate this "paradoxical" observation, we compared the metabolic changes during ischemia and the severity of subsequent reflow arrhythmias. Electrical instability during reperfusion was not related to accumulation of lactate, increase in cyclic AMP or decline in energy status. These were at a maximum in the severely ischemic myocardium. The reduced incidence of arrhythmias following severe (1% and 0.5% flow) as opposed to moderate ischemia, however, may have been associated with a major increase in glycogenolysis (from 1.2 to 7.4 and 7.6 mumol glucose equivalents/min per g dry weight).