Abstract 3547: Hydrogen Sulfide Therapy Attenuates Left Ventricular Dysfunction and Reduces Mortality in a Murine Model of Heart Failure
Hydrogen sulfide (H2S) is an endogenous signaling molecule with potent cytoprotective effects. In vivo evidence regarding its use in the treatment of heart failure (HF) is lacking. Therefore, we evaluated the therapeutic potential of H2S in a murine model of HF. HF was induced by subjecting mice to 60 min of left coronary artery (LCA) occlusion followed by reperfusion for 4 wk or by permanent ligation of the LCA for 4 wk. Additional experiments were performed in transgenic mice with cardiac-restricted overexpression of the H2S-generating enzyme, cytstathione gamma-lyase (αMHC-CGL-Tg+). High-resolution, 2-D echocardiography was performed at baseline and 4 wk post myocardial infarction (MI) to evaluate left ventricular (LV) dimensions and function (LV ejection fraction, EF). The H2S donor, IK1001 (100 μg/kg), or saline was administered at the time of reperfusion (intracardiac) and then daily (i.v.) for the first 7 days following MI. Both groups of mice developed profound ischemia-induced cardiomyopathy, as evidenced by an increase in LV dimensions and decreased EF. IK1001 protected against the structural and functional deterioration of the LV as seen by a reduction in LV dimensions and an improvement in EF compared to saline-treated animals. Similarly, αMHC-CGL-Tg+ displayed a clear protection against LV structural and functional impairment in response to ischemia-induced HF as well as improved survival in response to permanent myocardial ischemia. Combined these results suggest that either the administration of H2S donors or the modulation of the endogenous production of H2S may be of therapeutic benefit in the treatment of HF.