Abstract:
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.
