Resveratrol suppresses apoptosis in intact human cardiac tissue - in vitro model simulating extracorporeal circulation
Usta, E.; Mustafi, M.; Walker, T.; Ziemer, G.
Journal of Cardiovascular Surgery 52(3): 399-409
2011
ISSN/ISBN: 0021-9509 PMID: 21577194 Document Number: 655480
After cardioplegia and subsequent reperfusion of the myocardium as employed in cardiac surgery, ischemia/reperfusion injury of the myocardium can induce apoptosis. The aim of this study was to evaluate the anti-apoptotic properties of resveratrol, a phenolic phytoalexin present in grape skins and especially red wines during simulated cardioplegia (cp) and reperfusion (rep) in an in-vitro microperfusion model on human myocardium, which to our knowledge has not been investigated yet. Cardiac specimens were retrieved from the right auricle of patients undergoing elective coronary artery bypass graft before induction of cardiopulmonary bypass. Cardiac specimens, with resveratrol (10 µM) (N.=15) and w/o resveratrol (control, N.=15) were exposed in vitro to varying periods of cp/rep (30/10, 60/20, 120/40 min) in a microperfusion chamber. For detection of apoptosis anti-activated-caspase-3, PARP-1 cleavage immunostaining and real-time PCR for gene expression of cardiac cytokines like BNP, NF-κB1, NF-κB2, E-Selectin, Troponin and TNF-α were employed. the longer the cp/rep period lasted the higher were the rate of anti-activated-caspase-3 positive cardiomyocytes (21.26±2.07% ‑ 46.56±3.2%) and of PARP1-cleavage positive cardiomyocytes (23.29±2.16% ‑ 36.86±2.11%). Resveratrol group: apoptosis was suppressed significantly (P<0.05). Anti-activated-caspase-3 positive cardiomyocytes (13.45±4.35% ‑ 15.3±2.97%) and PARP1-cleavage positive cardiomyocytes (9.87±2.04% ‑ 11.77±3.42%). Resveratrol significantly suppressed the expression of BNP, NF-κB2, E-Selectin, Troponin and TNF-α in vitro (P<0.05). Resveratrol significantly suppresses apoptosis under our applied in vitro conditions. This finding warrants further studies aiming suppression of ischemia/reperfusion injury in clinical settings.