Melatonin protects against ischaemic-reperfusion myocardial damage

Objectives: Melatonin, a hormonal product of the pineal gland, is now known to be a multi-faceted free radical scavenger and anti-oxidant, Since littl e information is available regarding the action of melatonin on the heart, we studied the effects of melatonin on adult ventricular myocytes subjected to chemical hypoxia and reoxygenation. Methods: Adult rat ventricular myoc ytes were preloaded with tetramethylrhodamine (TMRM) in combination with on e of the following fluorophores: dichlorodihydrofluorescein diacetate (DCDH F), dihydrorhodamine 123 (DHR) of fluo 3 (Fluo) and then investigated with confocal laser scanning microscopy. Chemical hypoxia was induced by additio n of 1.5 mM KCN and 20 mM deoxyglucose to the superfusion buffer. Melatonin (50-100 muM) was added at different time intervals during the protocol. Re sults: Cells subjected to 12.5 min chemical hypoxia showed marked morpholog ical changes, increased fluorescence intensity of DCDHF, DHR and Flue, sugg esting Ca2+ accumulation and generation of H2O2 and reactive oxygen species . The number of cells showing increased fluorescence also increased signifi cantly. Melatonin (50 and 100 muM) caused a significant reduction in morpho logical changes, number of cells with increased fluorescence and fluorescen ce intensity of DHR and Fluo, (but not DUDHF). Conclusion: Melatonin effect ively reduced damage induced by chemical hypoxia in adult cardiomyocytes, p robably by virtue of its effects on reactive oxygen species generation and intracellular Ca2+ accumulation, (C) 2001 Academic Press.