Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function.
The recent discovery that hydrogen sulfide (H(2)S) is an endogenously produced gaseous second messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential of H(2)S as a cardioprotective agent. In the current study, we demonstrate that the delivery of H(2)S at the time of reperfusion limits infarct size and preserves left ventricular (LV) function in an in vivo model of myocardial ischemia-reperfusion (MI-R). This observed cytoprotection is associated with an inhibition of myocardial inflammation and a preservation of both mitochondrial structure and function after I-R injury. Additionally, we show that modulation of endogenously produced H(2)S by cardiac-specific overexpression of cystathionine gamma-lyase (alpha-MHC-CGL-Tg mouse) significantly limits the extent of injury. These findings demonstrate that H(2)S may be of value in cytoprotection during the evolution of myocardial infarction and that either administration of H(2)S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.
Elrod
John W
JW
Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Calvert
John W
JW
Morrison
Joanna
J
Doeller
Jeannette E
JE
Kraus
David W
DW
Tao
Ling
L
Jiao
Xiangying
X
Scalia
Rosario
R
Kiss
Levente
L
Szabo
Csaba
C
Kimura
Hideo
H
Chow
Chi-Wing
CW
Lefer
David J
DJ
D000818:Animals; D017209:Apoptosis; D004452:Echocardiography / Q000379:methods; D006352:Heart Ventricles / Q000473:pathology; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010101:Oxygen Consumption; D015427:Reperfusion Injury; D019210:Troponin I / Q000378:metabolism
D019210:Troponin I; D006862:Hydrogen Sulfide