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

The recent discovery that hydrogen sulfide (H₂S) is an endogenously produced gaseous second messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential of H₂S as a cardioprotective agent. In the current study, we demonstrate that the delivery of H₂S 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 H₂S by cardiac-specific overexpression of cystathionine γ-lyase (α-MHC-CGL-Tg mouse) significantly limits the extent of injury. These findings demonstrate that H₂S may be of value in cytoprotection during the evolution of myocardial infarction and that either administration of H₂S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.