Graded global ischemia and reperfusion. Cardiac function and lactate metabolism

The effect of global ischemia of different degrees of severity and reperfusion was studied in the isolated working rat heart. Four degrees of ischemia were induced by reducing the control total coronary flow of 8 ml/min to 0, 0.04, 0.4, or 0.8 ml/min for 30 minutes, after which the coronary flow was returned to the control level. After severe ischemia (0 and 0.04 ml/min ischemic coronary flow groups), recovery of contractility was to less than 30% of the control, pre-ischemic value of ventricular developed pressure and dP/dt, and irreversible cardiac contracture and an increased pacing threshold occurred. After moderate ischemia (0.4 and 0.8 ml/min ischemic coronary flow groups), contractile function recovered completely, ischemic contracture was rapidly reversible and the pacing threshold did not increase. The moderately ischemic groups were able to function at a stable, low level of contractility for the 30 minute ischemic period, whereas the severely ischemic groups had no contractile activity. The amount of calculated tissue lactate accumulation correlated with the occurrence of irreversible ischemic injury; the severely ischemic groups which failed to recover with reperfusion accumulated 3-5 times as much lactate as the moderately ischemic groups which recovered completely. The results suggest that relatively small differences in the severity of the ischemic condition can markedly affect the degree of tissue injury.