Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function

• DOI: 10.1073/pnas.0705891104
• Publication Date: 2007-09-19T01:04:45Z
• Authors: John W. Elrod; John W. Calvert; Joanna Morrison; Jeannette E. Doeller; David W. Kraus; Ling Tao; Xiangying Jiao; Rosario Scalia; Levente Kiss; Csaba Szabo; Hideo Kimura; Chi-Wing Chow; David J. Lefer
• Keywords: Inflammation; Male; 0301 basic medicine; Neutrophils; Heart Ventricles; Myocardium; Troponin I; Apoptosis; Mice, Transgenic; Mitochondria; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Oxygen Consumption; Echocardiography; Reperfusion Injury; Animals; Myocytes, Cardiac; Hydrogen Sulfide

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 γ-lyase (α-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.