Ischemic preconditioning of human myocardium: protein kinase C mediates a permissive role for alpha 1-adrenoceptors

Abstract

The purposes of this study were to determine whether ischemic preconditioning (IPC) 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) pre-treatment. 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.

Interleukin-10 Inhibits Postinjury Tumor Necrosis Factor-Mediated Human Vascular Smooth Muscle Proliferation

“…Ischemia was followed by 120 min reperfusion with normoxic Tyrode's solution. The ischemia-reperfusion protocol has previously been demonstrated to induce myocardial contractile dysfunction [11]. At end of reperfusion, all trabeculae were removed from the organ baths, weighed, rapidly frozen in liquid nitrogen, and stored at Ϫ70°C.…”

Role of protein kinase C as a cellular mediator of ischemic preconditioning: a critical review

“…PKC inhibition with chelerythrine also abolished the protection induced by stimulation of a-adrenoreceptors 11. Studies in humans [96]. Since these protocols were performed in in vitro settings and employed non-traditional preconditioning Speechly-Dick and colleagues subjected human right stimuli, their relevance to in vivo ischemic preconditioning atrial trabeculae to a preconditioning stimulus consisting of is not clear.…”

Differential Effect of Ischemic and Pharmacological Preconditioning on PKC Isoform Translocation in Adult Rat Cardiac Myocytes

“…In addition to reducing cell injury and death, IP decreases ventricular arrhythmias and leads to improved functional recovery of the heart during reperfusion [2,3]. The protective effect of ischemic preconditioning has been shown in dogs [4,5], pigs [6], rats [7,8], rabbits [9,10], mice [11] and humans [12]. Preconditioning can be activated not only by short ischemic insults but also by other means such as pharmacological agents, rapid ventricular pacing, and exposure to hypoxia or to myocardial stretch [13][14][15][16][17].…”