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 preconditioning (TPC) in human atrial trabeculae is mediated by alpha(1)-adrenoceptors and protein kinase C (PKC) and whether the protection of IPC is replicated with alpha(1)-adrenoceptor stimulation [alpha(1)-adrenoceptor 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 developed force was recorded. The trabeculae underwent 45 min of simulated ischemia (SI) and 120 min of reperfusion (I/R injury). IPC trabeculae received transient SI before I/R injury. alpha(1)-Adrenoceptor blockade with BE-2254 and PKC inhibition with chelerythrine were independently combined with IPC before I/R injury. alpha 1-PC before I/R was examined 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 kinase 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 tissue CK preservation conferred by IPC, but alpha(1)-PC does not replicate the protection of IPC.