Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Dec 2007
Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP 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 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.
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Can. J. Physiol. Pharmacol. · Dec 2007
Biography Historical ArticleAdventures in drug disposition: pas seulement pâté de foie.
Interindividual variability in drug disposition and effect has served to confound the optimization of drug therapy. Over my career, I have focused on delineating mechanisms that contribute to this variability, with the goal of improving the benefit : risk ratio when drug therapy is chosen as an intervention strategy. In this manuscript, I present some of our experimental findings that I believe have contributed to an increased understanding of variability in drug disposition and efficacy.