AIM S-propargyl-cysteine (SPRC), a structural analog of S-allylcysteine which is a major compound in garlic, has been proved to protect against myocardial ischemia through modulating H2S.In order to produce more stable and sustaining H2S, we developed SPRC controlled release formulation [SPRC (RS)], thenelucidated the protective effects on ischemic disease and the involved mechanisms on apoptosis, oxidation and angiogenesis.METHODS Heart failureandhind-limb ischemia model were induced by left coronary artery occlusion and femoral artery ligation.Echocardiographic indexes were recorded to determine the cardiac function.TTC staining was performed to determine the infarct size.Plasmatic level of H2S was detected by modified sulfide electrode.Activity of enzyme and expression of protein were determined by colorimetry and Western blotting.Angiography and immunofluorescence were performed to discover the density of vasculature.RESULTS The cardioprotective effects of SPRC(RS) on HF rats were confirmed by significant reduction of infarct size and improvement of cardiac function, with better effects than normal SPRC.SPRC (RS) modulated antioxidant defenses and protected against myocardial apoptosis.It also promoted angiogenesis in ischemic heart and hind-limb.These effects of SPRC(RS) were mediated by H2S.CONCLUSION SPRC (RS) played a protective rote in ischemic disease.More important, it exerted better effects than normal SPRC in all respects, providing a new perspective on H2S-mediated drug therapy.