title: Cardioprotective effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model.
abstract: OBJECTIVE
  Therapeutic hypothermia (TH) is widely used as a cardioprotective treatment for cardiac arrest. TH at 30-32°C during ischaemia and reperfusion has a cardioprotective effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a cardioprotective effect and to determine if this effect is mediated by nitric oxide (NO) and phosphatidylinositol 3'-kinase (PI3K).
  
  
  METHODS
  Langendorff perfusion of Sprague-Dawley rat hearts was initiated at 75 mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n=7): control group; ischaemia group, with 34°C TH during ischaemia for 30 min and reperfusion for 180 min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound.
  
  
  RESULTS
  TH reduced the left ventricle infarct size from 54.2 ± 14.8% of the control group to 11.9 ± 6.3% (ischaemia group, p<0.001) and to 23.5 ± 10.5% (reperfusion group, p<0.001). l-NAME, LY294002, and wortmannin reversed the cardioprotective effect of TH induced during reperfusion to 42.5 ± 10.6% (p=0.009), 40.9 ± 4.1% (p=0.021), and 51.9±13.0% (p<0.001), respectively. Circulatory temperatures reached 34°C within 5 min in all groups subjected to TH.
  
  
  CONCLUSIONS
  TH of 34°C showed a cardioprotective effect even with late initiation of cooling during reperfusion. The effect was mediated by NO and PI3K.
authors.affiliation: Department of Emergency Medicine, Hamamatsu University School of Medicine, Japan. toshiaki@hama-med.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Shuchun
authors.initials: S
authors.lastname: Yu
authors.forename: Takasumi
authors.initials: T
authors.lastname: Katoh
authors.forename: Katsunori
authors.initials: K
authors.lastname: Aoki
authors.forename: Shigehito
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D001831:Body Temperature; D004195:Disease Models, Animal; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000628:therapy*; D009569:Nitric Oxide / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D058539:Phosphatidylinositol 3-Kinase