Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening KATP channels

The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia-reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, +/- dP/dt(max), and the arrhythmia score. The results showed that the treatment of hearts with a H)S donor (40 mu mol/L NaHS) during reperfusion resulted in significant improvement in heart function compared with the I/R group (LVDP recovered to 85.0% +/- 6.4% vs. 35.0% +/- 6.1%. +dP/dt(max) recovered to 80.9% +/- 4.2% vs. 43.0% +/- 6.4%, and -dP/dt(max) recovered to 87.4% +/- 7.3% vs. 53.8% +/- 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group compared with the I/R group (1.5 +/- 0.2 vs. 4.0 +/- 0.4, respectively, p < 0.001). The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (K-ATP) blocker (10 mu mol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of KATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40 mu mol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100 mu mol/L NaHS. These findings provide the first evidence that H2S increases the open probability of KATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.