title: Resveratrol suppresses apoptosis in intact human cardiac tissue - in vitro model simulating extracorporeal circulation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Resveratrol significantly suppresses apoptosis under our applied in vitro conditions. This finding warrants further studies aiming suppression of ischemia/reperfusion injury in clinical settings.
authors.affiliation: Department of Cardiac and Vascular Surgery, University Hospital Tübingen, Tübingen, Germany. engin.usta@gmx.de
authors.forename: E
authors.initials: E
authors.lastname: Usta
authors.forename: M
authors.initials: M
authors.lastname: Mustafi
authors.forename: T
authors.initials: T
authors.lastname: Walker
authors.forename: G
authors.initials: G
authors.lastname: Ziemer
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010477:Perfusion; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D016207:Cytokines; D020011:Protective Agents; D013267:Stilbenes; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D000077185:Resveratrol