Synergy of isoflurane preconditioning and propofol postconditioning reduces myocardial reperfusion injury in patients

Clin Sci (Lond). 2011 Jul;121(2):57-69. doi: 10.1042/CS20100435.

Abstract

Either isoflurane preconditioning or high-dose propofol treatment has been shown to attenuate myocardial IRI (ischaemia/reperfusion injury) in patients undergoing CABG (coronary artery bypass graft) surgery. It is unknown whether isoflurane and propofol may synergistically attenuate myocardial injury in patients. The present study investigated the efficacy of IsoPC (isoflurane preconditioning), propofol treatment (postconditioning) and their synergy in attenuating postischaemic myocardial injury in patients undergoing CABG surgery using CPB (cardiopulmonary bypass). Patients (n = 120) selected for CABG surgery were randomly assigned to one of four groups (n = 30 each). After induction, anaesthesia was maintained either with fentanyl and midazolam (control; group C); with propofol at 100 μg x kg(-1) of body weight x min(-1) before and during CPB followed by propofol at 60 μg x kg(-1) of body weight x min(-1) for 15 min after aortic declamping (group P); with isoflurane 1-1.5% end tidal throughout the surgery (group I) or with isoflurane 1-1.5% end tidal before CPB and switching to propofol at 100 μg x kg(-1) of body weight x min(-1) during CPB followed by propofol at 60 μg x kg(-1) of body weight x min(-1) for 15 min after aortic declamping (group IP, i.e. IsoPC plus propofol postconditioning). A joint isoflurane and propofol anaesthesia regimen synergistically reduced plasma levels of cTnI (cardiac troponin I) and CK-MB (creatine kinase MB) and f-FABP (heart-type fatty acid-binding protein) (all P < 0.05 compared with control, group P or group I) and facilitated postoperative myocardial functional recovery. During reperfusion, myocardial tissue eNOS (endothelial NO synthase) protein expression in group IP was significantly higher, whereas nitrotyrosine protein expression was lower than those in the control group. In conclusion, a joint isoflurane preconditioning and propofol anaesthesia regimen synergistically attenuated myocardial reperfusion injury in patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anesthetics, Inhalation / therapeutic use
  • Anesthetics, Intravenous / therapeutic use
  • Antioxidants / metabolism
  • Coronary Artery Bypass / adverse effects
  • Cytokines / metabolism
  • Drug Synergism
  • Female
  • Hemodynamics
  • Humans
  • Inflammation Mediators / metabolism
  • Ischemic Postconditioning / methods*
  • Ischemic Preconditioning, Myocardial / methods*
  • Isoflurane / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Reperfusion Injury / prevention & control*
  • Nitric Oxide Synthase Type III / metabolism
  • Propofol / therapeutic use*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Antioxidants
  • Cytokines
  • Inflammation Mediators
  • 3-nitrotyrosine
  • Tyrosine
  • Isoflurane
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Propofol