ENDOGENOUS CATECHOLAMINES ARE NOT NECESSARY FOR ISCHEMIC PRECONDITIONING IN THE ISOLATED-PERFUSED RAT-HEART

Objective: The mechanism of the protective effect of ischaemic precond itioning in the myocardium is not yet known. The aim of this study was to test the hypothesis that endogenous myocardial catecholamines may be mediators of preconditioning. Methods: To test whether endogenous c atecholamines are involved in preconditioning, experiments were perfor med in hearts from rats which had been catecholamine depleted with eit her reserpine or B-hydroxydopamine. Experiments were also done to dete rmine if noradrenaline can mimic preconditioning. Results: Catecholami ne depletion with either reserpine or 6-hydroxydopamine had no effect on preischaemic coronary flow or cardiac function, Ischaemic precondit ioning (four episodes of 5 min global ischaemia and 5 min reperfusion) resulted in a significant increase in postischaemic cardiac function and a 50% decrease in lactate dehydrogenase (LDH) release following 30 min ischaemia and 30 min reperfusion compared with non-preconditioned hearts. Reserpine pretreatment did not affect the response to ischaem ia or to preconditioning, although LDH release tended to be greater th an in normal hearts, especially in the nonpreconditioned group. Althou gh 6-hydroxydopamine significantly increased postischaemic cardiac fun ction in the preconditioned group, no other index of ischaemic damage (for example, LDH release, left ventricular end diastolic pressure) wa s affected. Further studies showed that 10 nmol.min(-1) noradrenaline did not affect the severity of ischaemia, indicating that it does not mimic preconditioning. Conclusions: Endogenous catecholamines are not necessary for ischaemic preconditioning in isolated rat hearts and pla y little or no role in the functional responses to ischaemia.