Selective mitochondrial adenosine triphosphate-sensitive potassium channelactivation is sufficient to precondition human myocardium

Objectives: Recently, the mitochondrial adenosine triphosphate-sensitive po tassium channel has been suggested to be the final common effector of myoca rdial preconditioning. The purpose of this study is to determine whether se lective mitochondrial adenosine triphosphate-sensitive potassium channel ac tivation alone can precondition human myocardium from an ischemia/reperfusi on insult. Methods: Isolated human right atrial trabeculae were placed in tissue baths , paced, and subjected to 30 minutes of normothermic hypoxia (ischemia) fol lowed by 45 minutes of reoxygenation (reperfusion), Trabeculae were precond itioned with a selective mitochondrial adeno sine triphosphate-sensitive po tassium channel opener (diazoxide 30 mu mol/L) or a nonselective purinergic agonist, adenosine (125 mu mol/L), for 5 minutes (adenosine) followed by a 10-minute washout period, Developed force at end reperfusion (mean +/- sta ndard error) was compared with baseline, and tissue creatine kinase and ade nosine triphosphate levels were measured after ischemia/reperfusion. Results: Trabeculae subjected to ischemia/reperfusion exhibited 30% +/- 2% of baseline developed force, whereas trabeculae subjected to selective aden osine triphosphate-sensitive potassium channel opening (diazoxide) and nons elective purinergic agonist (adenosine) recovered to 55% +/- 7% and 46% +/- 3% of baseline developed force, respectively. Tissue creatine kinase activ ity was preserved in both the diazoxide- and adenosine-treated trabeculae ( 5.4 +/- 12 and 5.4 +/- 14 mu mol/L per gram wet tissue) compared with ische mia/reperfusion (1.8 +/- 0.2 U/mg wet tissue). Adenosine triphosphate level s at end reperfusion were also increased in the trabeculae treated with sel ective (diazoxide) and nonselective (adenosine) adenosine triphosphate-sens itive potassium channel opener (4.1 +/- 0.01 and 4.4 +/- 0.2 mu mol/L per g ram wet tissue) compared with trabeculae subjected to ischemia/reperfusion (1.5 +/- 0.1 mu mol/L per gram wet tissue). Conclusions: These results suggest that selective mitochondrial adenosine t riphosphate-sensitive potassium channel activation preconditions human myoc ardium and the protection conferred is equal to that of adenosine precondit ioning. Targeted openers of mitochondrial adenosine triphosphate-sensitive potassium channels promote constructive protection of myocellular energy le vels, contractile function, and cellular viability in human myocardium afte r ischemia/reperfusion.