Differential effect of preconditioning on post-ischaemic myocardial performance in the absence of substantial infarction and in extensively infarcted rat hearts.

Abstract

There is controversy concerning the beneficial effects of ischaemic preconditioning during short periods of ischaemia (stunning). The aim of the study was to investigate post-ischaemic myocardial performance after various periods of ischaemia in both non-preconditioned and preconditioned hearts and to compare these results with infarct volume estimation. Isolated perfused rat hearts were subjected to various periods of sustained ischaemia (15, 20, 30, and 45 min). Haemodynamic parameters, infarct size and lactate dehydrogenase (LDH) leakage were recorded in both preconditioned and non-preconditioned hearts. After 15 min of ischaemia, preconditioned hearts revealed significantly lower developed pressure than non-preconditioned hearts (80+/-4.1 vs. 95+/-0.3%, P=0.02). In the 20 min ischaemia group, preconditioning resulted in non-significantly lower developed pressure (76+/-3.1% in preconditioned hearts vs. 87+/-5.3% in non-preconditioned hearts, P=0.11). In these groups infarct volume was small and not different between non-preconditioned and preconditioned hearts. After 30 min of ischaemia, preconditioning significantly improved developed pressure (66+/-3.1% in preconditioned and 44+/-5% in non-preconditioned hearts, P=0.002). LDH leakage was significantly higher in non-preconditioned hearts compared with preconditioned hearts (16+/-2.3 vs. 9.0+/-1.3, P=0.04), whereas infarct volume was not (12.5+/-0.8 and 9.8+/-1.5, respectively, P=0.1). Non-preconditioned hearts of this group, subjected to inotropic stimulation at the end of reperfusion, responded poorly. Significantly higher developed pressure was attained by preconditioned hearts (150+/-3.1 vs. 123+/-7.5%, P=0.01). After 45 min of ischaemia, preconditioning resulted in 69% limitation of infarct volume (P<0.0001) and 53% reduction in LDH release (P=0.009). Developed pressure was 57+/-8.5% in preconditioned hearts and 32+/-4.5% in non-preconditioned hearts (P=0.02). When ischaemic insult results in minimally lethal injuries, preconditioned hearts do not have the advantage of not being prone to stunning rather than non-preconditioned. If ischaemic insult is potentially able to produce extensive infarction, improvement in post-ischaemic myocardial function is mainly due to infarct size limitation evoked by preconditioning.