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

Détails

ID Serval
serval:BIB_81E0B7AC040B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Myocardial impairment in chronic hypoxia is abolished by short aeration episodes: involvement of K+ATP channels.
Périodique
Experimental Biology and Medicine
Auteur(s)
Milano G., Bianciardi P., Corno A.F., Raddatz E., Morel S., von Segesser L.K., Samaja M.
ISSN
1535-3702 (Print)
ISSN-L
1535-3699
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
229
Numéro
11
Pages
1196-1205
Langue
anglais
Résumé
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% O(2)) 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% O(2), 30 min) and reoxygenated (94% O(2), 30 min) with or without 3 microM glibenclamide (nonselective K(+)(ATP) channel-blocker) or 100 microM 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 ratex 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.
Mots-clé
Animals, Anoxia/physiopathology, Apoptosis/physiology, Chronic Disease, Glyburide/pharmacology, Heart/drug effects, Heart/physiopathology, In Situ Nick-End Labeling, Male, Myocardial Reperfusion, Myocardium/pathology, Organ Culture Techniques, Oxidative Stress/physiology, Potassium Channel Blockers/pharmacology, Potassium Channels/drug effects, Potassium Channels/metabolism, Rats, Rats, Sprague-Dawley
Pubmed
Web of science
Création de la notice
24/01/2008 14:19
Dernière modification de la notice
03/03/2018 18:48
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