Purpose 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 (mKATP) 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 mKATP 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 KATP channels followed by inhibition of mPTP. H 2 gas may provide an effective adjunct strategy in patients with acute myocardial infarction receiving reperfusion therapy. © Springer Science+Business Media, LLC 2012.
CITATION STYLE
Yoshida, A., Asanuma, H., Sasaki, H., Sanada, S., Yamazaki, S., Asano, Y., … Kitakaze, M. (2012). H 2 mediates cardioprotection via involvements of K ATP channels and permeability transition pores of mitochondria in dogs. Cardiovascular Drugs and Therapy, 26(3), 217–226. https://doi.org/10.1007/s10557-012-6381-5
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