ISCHEMIC PRECONDITIONING OF HUMAN MYOCARDIUM - PROTEIN-KINASE-C MEDIATES A PERMISSIVE ROLE FOR ALPHA(1)-ADRENOCEPTORS

The purposes of this study were to determine whether ischemic precondi tioning (TPC) in human atrial trabeculae is mediated by alpha(1)-adren oceptors and protein kinase C (PKC) and whether the protection of IPC is replicated with alpha(1)-adrenoceptor stimulation [alpha(1)-adrenoc eptor preconditioning (alpha(1)-PC)]. Atrial trabeculae were obtained during coronary bypass surgery. The trabeculae were suspended in organ baths containing Tyrode solution and field stimulated at 1 Hz, and de veloped force was recorded. The trabeculae underwent 45 min of simulat ed ischemia (SI) and 120 min of reperfusion (I/R injury). IPC trabecul ae received transient SI before I/R injury. alpha(1)-Adrenoceptor bloc kade with BE-2254 and PKC inhibition with chelerythrine were independe ntly combined with IPC before I/R injury. alpha 1-PC before I/R was ex amined with alpha(1)-adrenergic agonist (phenylephrine) pretreatment. Improved recovery of developed force and higher tissue creatine kinase activity were present in IPC trabeculae, and the protective effect of IPC was eliminated with either alpha(1)-adrenoceptor blockade or PKC inhibition. alpha(1)-PC trabeculae also exhibited enhanced functional recovery after I/R injury but lacked preservation of tissue creatine k inase activity. PKC inhibition eliminated the functional protection of alpha(1)-PC. These results suggest that, in human atrial trabeculae, alpha(1)-adrenoceptors and PKC mediate, in part, the functional and ti ssue CK preservation conferred by IPC, but alpha(1)-PC does not replic ate the protection of IPC.