title: Hypothermia extends the cardioprotection by ischaemic preconditioning to coronary artery occlusions of longer duration.
abstract: OBJECTIVE
  To test the hypothesis that mild hypothermia potentiates the cardioprotection afforded by ischaemic preconditioning so that infarct size limitation can be obtained after coronary artery occlusion (CAO) durations which exceed the cardioprotective range (> 90 min) of either hypothermia or ischaemic preconditioning alone.
  
  
  METHODS
  Four groups of anaesthetized rats were subjected to different durations of CAO: (i) normothermia (N, 36.5-37.5 degrees C, n = 29), (ii) normothermia + ischaemic preconditioning (N + IP, 15 min CAO followed by 10 min of reperfusion, n = 35), (iii) hypothermia (H, 30-31 degrees C, n = 31) and (iv) hypothermia + ischaemic preconditioning (H + IP, n = 24). Infarct size (IA/AR) was determined after 3 hours of reperfusion using trypan blue to delineate the area at risk (AR) from non-risk region and nitroblue tetrazolium to delineate infarcted area (IA) from viable myocardium.
  
  
  RESULTS
  In N the CAO duration versus infarct size relation had a sigmoid shape with virtually no infarction occurring at 15 min CAO and 56 +/- 5% of the area at risk being infarcted at 30 min CAO reaching a plateau of 71 +/- 2% at 60 min CAO. Hypothermia produced a rightward shift of the relation resulting in an approximately 15 min delay in onset of infarction. Ischaemic preconditioning produced a similar reduction in infarct size (23 +/- 4%) at 30 min CAO compared to hypothermia (13 +/- 3%) but also limited infarct size at 45 min to 36 +/- 3% and at 60 min CAO to 50 +/- 3% suggesting a slowing of infarct progression. Neither intervention limited IA/AR produced by 120 min CAO. In H + IP, combined hypothermia and ischaemic preconditioning resulted in synergistic infarct size reduction so that at 45 min and 60 min CAO IA/AR was reduced to 17 +/- 3% and 23 +/- 3%, respectively, and even at 120 min CAO to 58 +/- 5%, which was significantly smaller than during normothermic control conditions (p < 0.05 vs. N).
  
  
  CONCLUSIONS
  Mild hypothermia limited IA/AR modestly but markedly enhanced the cardioprotection afforded by ischaemic preconditioning in the in situ rat heart so that irreversible damage produced by even prolonged coronary artery occlusions was limited.
authors.affiliation: Laboratory for Experimental Cardiology, Erasmus University Rotterdam, Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van den Doel
authors.forename: B C
authors.initials: BC
authors.lastname: Gho
authors.forename: S Y
authors.initials: SY
authors.lastname: Duval
authors.forename: R G
authors.initials: RG
authors.lastname: Schoemaker
authors.forename: D J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: P D
authors.initials: PD
authors.lastname: Verdouw
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003327:Coronary Disease / Q000150:complications* / Q000473:pathology; D007036:Hypothermia, Induced; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors