The effects of age and resveratrol on the hypoxic preconditioning protection against hypoxia-reperfusion injury: studies in rat hearts and human cardiomyocytes.

OBJECTIVES The loss of effectiveness of ischaemic preconditioning in protecting old hearts from ischaemia/reperfusion damage is thought to be due to low sirtuin 1 levels in old hearts. We sought to determine whether resveratrol (RES), an activator of sirtuin 1, would restore this protection to that seen with ischaemic preconditioning in young hearts. METHODS A Langendorff heart perfusion model was established in 80 old and 80 adult rats to test the effects of hypoxic preconditioning (HPC) and/or RES on preventing hypoxia-reperfusion (H/R) injury. The effects were further tested by comparing the effects of HPC and RES on cell survival rate and lactate dehydrogenase (LDH) in cardiomyocytes from 15 old and 15 young humans. RESULTS The HPC + RES group performed better in both adult and old groups than the corresponding H/R, HPC and RES groups, causing ∼50% in the adult and 40% in the old group restoration of left ventricular developed pressure and ∼90% in the adult and 80% in the old group restoration of dp/dtmax. HPC and RES each reduced apoptosis in both groups. The HPC + RES treatment showed an additive benefit in reducing apoptosis in the adult group but not in the old group. In H/R-treated young and old human cardiomyocytes, cell survival and LDH level were significantly improved in the RES + HPC group compared with the HPC group. CONCLUSIONS This study showed that RES lessened the ageing effect and enhanced the cardioprotective effect of HPC in older individuals.