Melatonin prevents cardioprotection induced by a multi-cycle ischaemic preconditioning protocol in the isolated perfused rat heart
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The powerful cardioprotective actions of melatonin, the chief secretory product of the pineal gland, have been attributed largely to its free radical-scavenging properties. Free radicals play an important role in the triggering action of ischaemic preconditioning, the phenomenon whereby exposure of the heart to one or more short episodes of ischaemia leads to protection against a subsequent long period of ischaemia. The aim of this study was, therefore, to establish whether melatonin, in view of its free radical-scavenging ability, would affect the beneficial actions of preconditioning. Isolated, perfused, working hearts were subjected to 1 × 5 minute or 3 × 5 min ischaemic preconditioning protocols, in the presence or absence of melatonin (50 μM), followed by 20 minutes global ischaemia and 30 minutes reperfusion. Use was also made of sodium nitroprusside (100 μM), a nitric oxide (NO) donor and preconditioning mimetic. Using functional recovery as the endpoint, melatonin abolished the cardioprotective effects of a multi-cycle (3 × 5 min) preconditioning protocol, while having no effect on a one-cycle (1 × 5 min) protocol or SNP (1 × 5 or 3 × 5 min) preconditioning. The results suggest that free radicals play an important role in the cardioprotection induced by a multi-cycle ischaemic preconditioning protocol and that this process could be attenuated by a potent scavenger such as melatonin.