CARDIOPROTECTION IN AN IN-VITRO MODEL OF HYPOXIC PRECONDITIONING

Short periods of myocardial ischemia appear to provide protection agai nst subsequent prolonged ischemic episodes in experimental animals and in man. This phenomenon, known as ischemic preconditioning, has not y et been characterized at the cellular or molecular levels; however, ti ssue hypoxia appears to be required. In this study, we used a previous ly developed method for hypoxic cardiac myocyte culture in order to es tablish a model for ischemic (or hypoxic) preconditioning in cell cult ure. We demonstrate that cultured neonatal rat cardiac myocytes precon ditioned by 25 min of exposure to hypoxia followed by reoxygenation we re protected against membrane damage for up to 6 h of prolonged severe hypoxia, as determined by arachidonic acid release and contractile re covery. In contrast, non-preconditioned myocytes exhibited significant hypoxic damage after 2-4 h. Pretreatment of cells with PMA, a tumor-p romoting phorbol ester, mimicked the protective effects of hypoxic pre conditioning; pretreatment with the muscarinic cholinergic agonist car bachol had no effect, Our data suggests that isolated myocytes in cult ure remain competent to be preconditioned by hypoxia, through a pathwa y that may involve the activation of protein kinase C.