Myocardial impairment in chronic hypoxia is abolished by short aeration episodes: Involvement of K+ ATP channels

Giuseppina Milano, Paola Bianciardi, Antonio F. Corno, Eric Raddatz, Sandrine Morel, Ludwig K. Von Segesser, Michele Samaja

Research output: Contribution to journalArticle

Abstract

In vivo exposure to chronic hypoxia is considered to be a cause of myocardial dysfunction, thereby representing a deleterious condition, but repeated aeration episodes may exert some cardioprotection. We investigated the possible role of ATP-sensitive potassium channels in these mechanisms. First, rats (n = 8/group) were exposed for 14 days to either chronic hypoxia (CH; 10% O2) or chronic hypoxia with one episode/day of 1-hr normoxic aeration (CH+A), with normoxia (N) as the control. Second, isolated hearts were Langendorff perfused under hypoxia (10% O2, 30 min) and reoxygenated (94% O2, 30 min) with or without 3 μM glibenclamide (nonselective K+ ATP channel-blocker) or 100 μM diazoxide (selective mitochondrial K+ ATP channel-opener). Blood gasses, hemoglobin concentration, and plasma malondialdehyde were similar in CH and CH+A and in both different from normoxic (P <0.01), body weight gain and plasma nitrate/nitrite were higher in CH+A than CH (P <0.01), whereas apoptosis (number of TUNEL-positive nuclei) was less in CH+A than CH (P <0.05). During in vitro hypoxia, the efficiency (ratio of ATP production/pressure x rate product) was the same in all groups and diazoxide had no measurable effects on myocardial performance, whereas glibenclamide increased end-diastolic pressure more in N and CH than in CH+A hearts (P <0.05). During reoxgenation, efficiency was markedly less in CH with respect to N and CH+A (P <0.0001), and rate x pressure product remained lower in CH than N and CH+A hearts (P <0.001), but glibenclamide or diazoxide abolished this difference. Glibenclamide, but not diazoxide, decreased vascular resistance in N and CH (P <0.005 and <0.001) without changes in CH+A. We hypothesize that cardioprotection in chronically hypoxic hearts derive from cell depolarization by sarcolemmal K + ATP blockade or from preservation of oxidative phosphorylation efficiency (ATP turnover/myocardial performance) by mitochondrial K+ ATP opening. Therefore K+ ATP channels are involved in the deleterious effects of chronic hypoxia and in the cardioprotection elicited when chronic hypoxia is interrupted with short normoxic aeration episodes.

Original languageEnglish
Pages (from-to)1196-1205
Number of pages10
JournalExperimental Biology and Medicine
Volume229
Issue number11
Publication statusPublished - Dec 2004

Keywords

  • Apoptosis
  • Diazoxide
  • Glibenclamide
  • Hypoxia
  • Reoxygenation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Milano, G., Bianciardi, P., Corno, A. F., Raddatz, E., Morel, S., Von Segesser, L. K., & Samaja, M. (2004). Myocardial impairment in chronic hypoxia is abolished by short aeration episodes: Involvement of K+ ATP channels. Experimental Biology and Medicine, 229(11), 1196-1205.