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- Title
H Mediates Cardioprotection Via Involvements of K Channels and Permeability Transition Pores of Mitochondria in Dogs.
- Authors
Yoshida, Akemi; Asanuma, Hiroshi; Sasaki, Hideyuki; Sanada, Shoji; Yamazaki, Satoru; Asano, Yoshihiro; Shinozaki, Yoshiro; Mori, Hidezo; Shimouchi, Akito; Sano, Motoaki; Asakura, Masanori; Minamino, Tetsuo; Takashima, Seiji; Sugimachi, Masaru; Mochizuki, Naoki; Kitakaze, Masafumi
- Abstract
Purpose: Inhalation of hydrogen (H) gas has been shown to limit infarct size following ischemia-reperfusion injury in rat hearts. However, H 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) and subsequent inhibition of mitochondrial permeability transition pores (mPTP) mediates the infarct size-limiting effect of H 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 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 blocker), or atractyloside (Atr; a mPTP opener). Results: Systemic hemodynamic parameters did not differ among the groups. Nevertheless, H 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 gas (42.0 ± 2.2% with 5-HD and 45.1 ± 2.7% with Atr; both p < 0.001 vs. H 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 was not due to anti-oxidative actions or effects on the NADH dehydrogenase pathway. Conclusions: Inhalation of H gas reduces infarct size in canine hearts via opening of mitochondrial K channels followed by inhibition of mPTP. H gas may provide an effective adjunct strategy in patients with acute myocardial infarction receiving reperfusion therapy.
- Subjects
ISCHEMIA; REPERFUSION injury; LABORATORY rats; HEMODYNAMICS; HEART diseases; HEART blood-vessels
- Publication
Cardiovascular Drugs & Therapy, 2012, Vol 26, Issue 3, p217
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-012-6381-5