Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats

The role of hydrogen sulfide ( H2S) in myocardial infarction ( MI) has not been previously studied. We therefore investigated the effect of H2S in a rat model of MI in vivo. Animals were randomly divided into three groups ( n = 80) and received either vehicle, 14 mu mol/kg of sodium hydrosulfide ( NaHS), or 50 mg/kg propargylglycine ( PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle-treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Plasma H2S concentration was significantly increased after MI ( 59.2 +/- 7.16 mu M) compared with the baseline concentration ( i.e., 38.2 +/- 2.07 mu M before MI; P < 0.05). Elevated plasma H2S after MI was abolished by treatment of animals with PAG ( 39.2 +/- 5.02 mu M). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS ( 71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/- 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H2S was cardioprotective in the rat model of MI. PAG reduced endogenous H2S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H2S might provide a novel approach to the treatment of MI.