Hydrogen sulfide contributes to cardioprotection during ischemia–reperfusion injury by opening KATPchannels

Abstract

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/dtmax, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 μmol/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/dtmaxrecovered to 80.9% ± 4.2% vs. 43.0% ± 6.4%, and –dP/dtmaxrecovered 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 (KATP) blocker (10 μmol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of KATPchannels from 0.07 ± 0.03 to 0.15 ± 0.08 after application of 40 μmol/L NaHS and from 0.07 ± 0.03 to 0.36 ± 0.15 after application of 100 μmol/L NaHS. These findings provide the first evidence that H2S increases the open probability of KATPin cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.