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

Abstract

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 ischemiareperfusion (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 ␥-lyase (␣-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.

Selective fluorescent probes for live-cell monitoring of sulphide

“…H 2 S, or aqueous sulphide, elicits diverse physiological responses, including modulation of blood pressure and reduction of ischemia reperfusion injury [3][4][5] , exertion of anti-inflammatory effects 6 and reduction of metabolic rate 7 . The production of H 2 S is catalysed by the two pyridoxal 5′-phosphate-dependent enzymes, cystathionine β-synthase (CBS) 8 , and cystathionine γ-lyase 9 , and indirectly, via a pyridoxal 5′-phosphateindependent enzyme, 3-mercaptopyruvate sulphurtransferase 10 .…”

Hydrogen Sulfide: A Rescue Molecule for Mucosal Defence and Repair

“…A number of recent studies suggest that the ability of H 2 S to maintain mitochondrial function in the face of challenges such as ischemia may underlie some of the beneficial effects of this mediator. This has been elegantly demonstrated by Elrod et al [14] using an experimental model of myocardial ischemia-reperfusion. H 2 S was found to reduce myocardial inflammation and to preserve mitochondrial structure and function in this model.…”

Regulation of cardiovascular cell function by hydrogen sulfide (H2S)

“…41 This action has also been observed in mice receiving 1 mg kg À1 NaHS at reperfusion in an in vivo model. 42 NaHS also caused a concentration-dependent reduction in the rate of pace maker firing in rabbit pacemaker cells in sinoatrial nodes. This negative chronotropic effect was blocked in the presence of glibenclamide, again implicating an increase in potassium efflux through the K ATP channels to mediate the effect in pacemaker cells.…”

“…Direct administration of NaHS (50 mg kg À1 ) at reperfusion in an in vivo mouse model also caused substantial reduction of infarct size associated with preservation of mitochondrial function. 42 Rossoni et al 51 have reported cardioprotection from S-diclofenac, an H 2 S donating derivative of the nonsteroidal anti-inflammatory drug diclofenac, in isolated rabbit hearts subjected to low-flow ischemia. The cardioprotection was attenuated in the presence of glibenclamide, suggesting a potential role for K ATP channel opening in mediating cardioprotection with S-diclofenac.…”