ADENOSINE PRECONDITIONING OF HUMAN MYOCARDIUM IS DEPENDENT UPON THE ATP-SENSITIVE K+ CHANNEL

Evidence supports the involvement of adenosine receptor stimulation an d activation of K-ATP channels in ischemic preconditioning of human my ocardium. It is unknown, however, whether protection mediated by adeno sine receptors is dependent upon the It, channel in the human heart. T he purpose of this study was to determine whether adenosine-mediated p rotection against a simulated ischemia-reperfusion injury in human myo cardium is dependent upon K-ATP channels. Isolated human right atrial trabeculae were placed in tissue baths at 37 degrees C, oxygenated wit h a modified Tyrode solution, and field stimulated at 1 Hz. Trabeculae were subjected to 45 min of normothermic simulated ischemia (hypoxic, substrate-free buffer with pacing at 3 Hz.) and 60 min of reperfusion (I/R trabeculae). Trabeculae were preconditioned with simulated ische mia (IPC trabeculae) or adenosine receptor stimulation (adenosine, 125 mu mol/l) for 5 min (ADO trabeculae) prior to simulated ischemic-repe rfusion injury. Inhibition of the K-ATP channel with glibenclamide (10 mu mol/l) was combined with adenosine pretreatment (ADO + GLI trabecu lae) or alone (GLI trabeculae) prior to simulated ischemic-reperfusion injury. Developed force (DF) at end reperfusion (mean +/- S.E.) was c ompared to baseline developed force, and tissue creatine kinase (CK) a ctivity at end reperfusion was measured, I/R trabeculae showed 27 +/- 2% of baseline DF, whereas IPC trabeculae or ADO trabeculae showed 50 +/- 4% and 43 +/- 3% of baseline DF, respectively, ADO + GLI trabecula e showed 25 +/- 2% and GLI trabeculae showed 23 +/- 4% of baseline DF. Tissue CK activity was enhanced in the IPC and ADO trabeculae (433 +/ - 63 U/g wet myocardium, and 415 +/- 28 U/g wet myocardium, respective ly), I/R trabeculae had 196 +/- 26 U/g wet myocardium and ADO + GLI tr abeculae had 277 +/- 38 U/g wet myocardium at end reperfusion. The res ults suggest that ischemic preconditioning and adenosine receptor stim ulation confer functional protection against simulated ischemic-reperf usion, and adenosine mediated protection is eliminated by K-ATP channe l inhibition in human myocardium. (C) 1997 Academic Press Limited.