ACUTE ISCHEMIC PRECONDITIONING AND CHRONIC HYPOXIA INDEPENDENTLY INCREASE MYOCARDIAL TOLERANCE TO ISCHEMIA

Objective: Myocardial adaptation has been reported to result from mild but chronic ischaemia in the hearts of patients with coronary artery disease. The aim of this study was to test the hypothesis that the responses of the chronically hypoxic myocardium to an episode of severe ischaemia, or the effects of acute ischaemic preconditioning on myocardial function after subsequent fatal ischaemia, may differ between the normoxic and the chronically hypoxic myocardium. Methods: A rat model of three week hypoxia (10% O-2) was used to simulate tissue hypoxia caused by chronic ischaemia. In isolated isovolumetrically contracting hearts perfused with oxygenated erythrocyte-containing Tyrode solution, systolic and diastolic functions during a 15 or 20 min period of ischaemia and reperfusion were measured in the normoxic control and chronically hypoxic groups. Results: Increases in diastolic pressure during ischaemia were smaller and the recovery of developed pressure during reperfusion was greater in the chronically hypoxic group than in the normoxic group. The hearts of the normoxic group never recovered from ischaemic damage after 20 min ischaemia. The beneficial effects of acute preconditioning with 5 min ischaemia on myocardial function were observed after 15 min ischaemia in the normoxic group, and during and after 20 min ischaemia in the chronically hypoxic group. Changes in lactate production and high energy phosphates could not explain the increased tolerance to ischaemia in the chronically hypoxic group. Conclusions: Chronic hypoxia increased myocardial tolerance to ischaemia, and acute ischaemic preconditioning increased the tolerance further. Thus chronic hypoxia and acute ischaemic preconditioning independently activate protective mechanisms against ischaemia; the mechanisms may differ between the two types of insult.