title: Ischaemic postconditioning: does cardioplegia influence protection?
abstract: OBJECTIVE
  Ischaemic postconditioning attenuates reperfusion injury and may be a useful adjunct to cardiac surgery. We examined the efficacy of postconditioning following ischaemic protection with cardioplegic arrest and the importance of index ischaemia and cardioplegia formulation.
  
  
  METHODS
  Isolated Langendorff-perfused rat hearts were subjected to varying durations (30, 45 or 60 min) of global (37°C) ischaemia and then reperfused; functions such as left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate and coronary flow were assessed throughout reperfusion, and infarct size measured after 120 min of reperfusion. Two studies were conducted. Study 1 compared recovery of function and infarct size after varying durations (30, 45 or 60 min) of ischaemia alone and ischaemia preceded by protection with St Thomas' Hospital cardioplegic solution, with or without a postconditioning protocol (six cycles of 10-s reperfusion and 10-s ischaemia). Study 2 investigated the importance of magnesium in cardioplegia [low magnesium (1.2 mmol/l) or zero magnesium (0 mmol/l)] on postconditioning protection after varying durations of ischaemia (30, 45 or 60 min).
  
  
  RESULTS
  Postconditioning enhanced protection after 30-min ischaemia alone [left ventricular developed pressure at 60-min reperfusion recovered to 34 ± 1% after ischaemia alone and 45 ± 2% after postconditioning (P < 0.05); infarct size was 21 ± 4 and 11 ± 1%, respectively (P < 0.05)], but there were no differences after 45 or 60 min of ischaemia. Increasing ischaemic durations reduced recovery, and cardioplegia was protective during shorter ischaemia but protection diminished as ischaemic duration increased. Postconditioning was ineffective after cardioplegia protection at all ischaemic durations. However, postconditioning after cardioplegia containing zero magnesium was efficacious for 60 min of ischaemia [left ventricular developed pressure at 60-min reperfusion was 41 ± 2% (P < 0.05) vs. 31 ± 3%; infarct size was 30 ± 7 vs. 56 ± 6%, respectively (P < 0.05)], but was ineffective for shorter periods of ischaemia.
  
  
  CONCLUSIONS
  We conclude that postconditioning does not enhance the protective effect of St Thomas' Hospital cardioplegia (under these strict experimental conditions); however, the efficacy of postconditioning correlates with the magnesium concentration of the cardioplegic solution, which may imply involvement of magnesium on mitochondria during ischaemia. There is a limited window of postconditioning protection dependent on the duration of the index ischaemia.
authors.affiliation: Cardiac Surgical Research/Cardiothoracic Surgery,  The Rayne Institute (King's College London), Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London,  UK.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Maruyama
authors.forename: David J
authors.initials: DJ
authors.lastname: Chambers
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000008:administration & dosage; D002122:Calcium Chloride / Q000008:administration & dosage; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006324:Heart Arrest, Induced / Q000379:methods*; D006339:Heart Rate / Q000502:physiology; D057775:Ischemic Postconditioning / Q000379:methods*; D008274:Magnesium / Q000008:administration & dosage; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011189:Potassium Chloride / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D001639:Bicarbonates; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride