Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 217-226 |
| Number of pages | 10 |
| Journal | Cardiovascular Drugs and Therapy |
| Volume | 26 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2012 Jun |
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Keywords
- Hydrogen gas
- Mitochondrial KATP channel
- Mitochondrial permeability transition pore
- Myocardial infarction
- Reperfusion injury
ASJC Scopus subject areas
- Pharmacology (medical)
- Cardiology and Cardiovascular Medicine
- Pharmacology
Cite this
H 2 mediates cardioprotection via involvements of K ATP channels and permeability transition pores of mitochondria in dogs. / 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.
In: Cardiovascular Drugs and Therapy, Vol. 26, No. 3, 06.2012, p. 217-226.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - H 2 mediates cardioprotection via involvements of K ATP channels and permeability transition pores of mitochondria in dogs
AU - Yoshida, Akemi
AU - Asanuma, Hiroshi
AU - Sasaki, Hideyuki
AU - Sanada, Shoji
AU - Yamazaki, Satoru
AU - Asano, Yoshihiro
AU - Shinozaki, Yoshiro
AU - Mori, Hidezo
AU - Shimouchi, Akito
AU - Sano, Motoaki
AU - Asakura, Masanori
AU - Minamino, Tetsuo
AU - Takashima, Seiji
AU - Sugimachi, Masaru
AU - Mochizuki, Naoki
AU - Kitakaze, Masafumi
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Hydrogen gas
KW - Mitochondrial KATP channel
KW - Mitochondrial permeability transition pore
KW - Myocardial infarction
KW - Reperfusion injury
UR - http://www.scopus.com/inward/record.url?scp=84864459708&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864459708&partnerID=8YFLogxK
U2 - 10.1007/s10557-012-6381-5
DO - 10.1007/s10557-012-6381-5
M3 - Article
C2 - 22527618
AN - SCOPUS:84864459708
VL - 26
SP - 217
EP - 226
JO - Cardiovascular Drugs and Therapy
JF - Cardiovascular Drugs and Therapy
SN - 0920-3206
IS - 3
ER -