Ischemic Tolerance of the Heart by Adaptation to Chronic Hypoxia is Suppressed by High Subchronic Carbon Monoxide Exposure
Authors: Barbé, Christine; Rochetaing, Annie; Kreher, Paul
Source: Inhalation Toxicology, Volume 13, Number 3, 1 March 2001 , pp. 219-232(14)
Publisher: Informa Healthcare
Abstract:This study was designed to investigate whether exposure to carbon monoxide (CO) could alter the ischemic tolerance induced by chronic hypoxia. We aimed to determine whether chronic hypoxia-induced cardiovascular adaptation was modified during the return to normoxia or by subchronic CO exposure. The degree of resistance to an in vitro transient ischemia was measured, using the Langendorff method, in hearts from rats previously exposed to chronic hypoxic hypoxia and/or subchronic CO exposure to 600 ppm. Chronic hypoxia decreased ischemic contracture (15.6 ± 04.9 vs. 60.8 ± 07.7%) and improved both contractile recovery (59.6 ± 07.3 vs. 21.8 ± 06.8%) and ventricular arrhythmia during reperfusion (0 vs. 45%) compared to a control normoxic group. However, in our chronic hypoxia regression model many parameters returned near to control values except for the persistence of cardiomegaly, a significant decrease in both ischemic contracture (22.0 ± 04.9 vs. 60.8 ± 07.7%), and ventricular tachycardia (25 vs. 45%). CO exposure alone increased the coronary flow and improved both contractile recovery (42.6 ± 7.2 vs. 21.8 ± 6.8%) and ventricular arrhythmia (16.7 vs. 45%) without altering the action potential shape. These two models causing tissue hypoxia induced the same degree of polycythemia or cardiomegaly and provided similar ischemic tolerance. CO exposure after chronic hypoxia exacerbated ischemic contracture (69.3 ± 10.5 vs. 22.0 ± 14.5%) and ventricular tachycardia incidence (100 vs. 50%) but with significant alteration in contractile recovery (12.7 ± 10.5%) compared to the chronic hypoxia or CO exposure. Thus, CO exposure completely suppressed the chronic hypoxia-induced ischemic tolerance.
Document Type: Research Article
Affiliations: Laboratoire de Préconditionnement et de Remodelage du Myocarde, Faculté des Sciences, Angers Cedex, France
Publication date: March 1, 2001