Hydrogen Sulfide Contributes to Cardioprotection During Ischemia-Reperfusion Injury by Opening K ATP Channels

Can J Physiol Pharmacol. 2007 Dec;85(12):1248-53. doi: 10.1139/Y07-120.

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/dt max, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 micromol/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 micromol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of K ATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40 mumol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100 mumol/L NaHS. These findings provide the first evidence that H2S increases the open probability of K ATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control
  • Cardiotonic Agents / pharmacology*
  • Cells, Cultured
  • Glyburide / pharmacology
  • Heart / physiopathology
  • Hydrogen Sulfide / pharmacology*
  • In Vitro Techniques
  • Male
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / physiology*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Sulfides / pharmacology

Substances

  • Cardiotonic Agents
  • Potassium Channel Blockers
  • Potassium Channels
  • Sulfides
  • sodium bisulfide
  • Glyburide
  • Hydrogen Sulfide