title: H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs.
abstract: OBJECTIVE
  Inhalation of hydrogen (H(2)) gas has been shown to limit infarct size following ischemia-reperfusion injury in rat hearts. However, H(2) gas-induced cardioprotection has not been tested in large animals and the precise cellular mechanism of protection has not been elucidated. We investigated whether opening of mitochondrial ATP-sensitive K+ channels (mK(ATP)) and subsequent inhibition of mitochondrial permeability transition pores (mPTP) mediates the infarct size-limiting effect of H(2) gas in canine hearts.
  
  
  METHODS
  The left anterior descending coronary artery of beagle dogs was occluded for 90 min followed by reperfusion for 6 h. Either 1.3% H(2) or control gas was inhaled from 10 min prior to start of reperfusion until 1 h of reperfusion, in the presence or absence of either 5-hydroxydecanoate (5-HD; a selective mK(ATP) blocker), or atractyloside (Atr; a mPTP opener).
  
  
  RESULTS
  Systemic hemodynamic parameters did not differ among the groups. Nevertheless, H(2) gas inhalation reduced infarct size normalized by risk area (20.6±2.8% vs. control gas 44.0±2.0%; p<0.001), and administration of either 5-HD or Atr abolished the infarct size-limiting effect of H(2) gas (42.0±2.2% with 5-HD and 45.1±2.7% with Atr; both p<0.001 vs. H(2) group). Neither Atr nor 5-HD affected infarct size per se. Among all groups, NAD content and the number of apoptotic and 8-OHdG positive cells was not significantly different, indicating that the cardioprotection afforded by H(2) was not due to anti-oxidative actions or effects on the NADH dehydrogenase pathway.
  
  
  CONCLUSIONS
  Inhalation of H(2) gas reduces infarct size in canine hearts via opening of mitochondrial K(ATP) channels followed by inhibition of mPTP. H(2) gas may provide an effective adjunct strategy in patients with acute myocardial infarction receiving reperfusion therapy.
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Akito
authors.initials: A
authors.lastname: Shimouchi
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003652:Decanoic Acids / Q000494:pharmacology; D004285:Dogs; D006859:Hydrogen / Q000627:therapeutic use*; D006880:Hydroxy Acids / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D026902:Potassium Channel Blockers; C052853:5-hydroxydecanoic acid; D006859:Hydrogen