Cardioprotection in an in vitro model of hypoxic preconditioning

Keith A. Webster, Daryl J. Discher, Nanetter H. Bishopric

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Short periods of myocardial ischemia appear to provide protection against subsequent prolonged ischemic episodes in experimental animals and in man. This phenomenon, known as ischemic preconditioning, has not yet been characterized at the cellular or molecular levels; however, tissue hypoxia appears to be required. In this study, we used a previously developed method for hypoxic cardiac myocyte culture in order to establish a model for ischemic (or hypoxic) preconditioning in cell culture. We demonstrate that cultured neonatal rat cardiac myocytes preconditioned by 25 min of exposure to hypoxia followed by reoxygenation were protected against membrane damage for up to 6 h of prolonged severe hypoxia, as determined by arachidonic add release and contractile recovery. In contrast, non-preconditioned myocytes exhibited significant hypoxic damage after 2-4 h. Pretreatment of cells with PMA, a tumor-promoting phorbol ester, mimicked the protective effects of hypoxic preconditioning; pretreatment with the muscarinic cholinergic agonist carbachol had no effect. Our data suggests that isolated myocytes in culture remain competent to be preconditioned by hypoxia, through a pathway that may involve the activitation of protein kinase C.

Original languageEnglish (US)
Pages (from-to)453-458
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number1
DOIs
StatePublished - Jan 1995

Keywords

  • Cardiac
  • Ischemia
  • Myocytes
  • Protein kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

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