Resveratrol suppresses apoptosis in intact human cardiac tissue - in vitro model simulating extracorporeal circulation

J Cardiovasc Surg (Torino). 2011 Jun;52(3):399-409.

Abstract

Aim: 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.

Methods: 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.

Control group: 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).

Conclusion: Resveratrol significantly suppresses apoptosis under our applied in vitro conditions. This finding warrants further studies aiming suppression of ischemia/reperfusion injury in clinical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / drug effects*
  • Biopsy
  • Caspase 3 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Extracorporeal Circulation / adverse effects*
  • Female
  • Gene Expression Regulation
  • Heart Arrest, Induced / adverse effects*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Myocardial Reperfusion Injury / enzymology
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / pathology
  • Perfusion
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protective Agents / pharmacology*
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stilbenes / pharmacology*
  • Time Factors

Substances

  • Cytokines
  • Protective Agents
  • Stilbenes
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Resveratrol