Myocardial Impairment in Chronic Hypoxia is Abolished by Short Aeration Episodes: Involvement of K+ATP Channels
- 1 December 2004
- journal article
- research article
- Published by Frontiers Media SA in Experimental Biology and Medicine
- Vol. 229 (11), 1196-1205
- https://doi.org/10.1177/153537020422901115
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.Keywords
This publication has 34 references indexed in Scilit:
- Myocardial metabolic changes during pediatric cardiac surgery: A randomized study of 3 cardioplegic techniquesThe Journal of Thoracic and Cardiovascular Surgery, 2004
- Responses of chronically hypoxic rat hearts to ischemia: KATP channel blockade does not abolish increased RV tolerance to ischemiaAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Effects of mitochondrial KATP modulators on cardioprotection induced by chronic high altitude hypoxia in ratsCardiovascular Research, 2002
- Effect of ATP-Sensitive Potassium Channel Inhibition on Resting Coronary Vascular Responses in HumansCirculation Research, 2002
- Sarcolemmal and Mitochondrial KATPChannels Mediate Cardioprotection in Chronically Hypoxic HeartsJournal of Molecular and Cellular Cardiology, 2001
- Nitric Oxide Activates the Sarcolemmal KATPChannel in Normoxic and Chronically Hypoxic Hearts by a Cyclic GMP-dependent MechanismJournal of Molecular and Cellular Cardiology, 2001
- Adaptation to High Altitude Hypoxia Protects the Rat Heart Against Ischemia-induced Arrhythmias. Involvement of Mitochondrial KATPChannelJournal of Molecular and Cellular Cardiology, 1999
- Protective Effects of Intermittent Hypoxic Adaptation on Myocardium and Its MechanismsNeurosignals, 1999
- KATPChannel Activation in a Rabbit Model of Chronic Myocardial HypoxiaJournal of Molecular and Cellular Cardiology, 1997
- Chronic Hypoxemia Depresses Global Ventricular Function and Predisposes to the Depletion of High-Energy Phosphates during Cardioplegic Arrest: Implications for Surgical Repair of Cyanotic Congenital Heart DefectsThe Annals of Thoracic Surgery, 1984