Acute ischemic preconditioning and high subchronic CO exposure independently increase myocardial tolerance to ischemia.
This study was designed to investigate whether exposure to carbon monoxide (CO) could alter or raise the ischemic tolerance induced by preconditioning. To this end, isolated rat hearts were aerobically perfused for 20 min. Hearts were then randomized to two groups: (1) a further 20-min aerobic perfusion, and (2) ischemic preconditioning (2 cycles of 5 min of ischemia followed by 5 min of reperfusion). Hearts were then subjected to 25 min of low-flow (0.3 ml/min.) global ischemia (37 degrees C) and 30 min of reperfusion. In parallel studies, the same protocols were performed in hearts from rats previously exposed to subchronic CO (600 ppm for 2 wk). Ischemic preconditioning accelerated the development of ischemic contracture (onset = 6.0 +/- 0.3 vs. 8.6 +/- 0.9 min), increased the preischemic coronary flow (19.0 +/- 1.0 vs. 11.6 +/- 0.6 ml/min/g), improved contractile recovery (73.7 +/- 8.9 vs. 30.8 +/- 7.5%), but was without effect on reactive hyperemia (151.2 +/- 4.7 vs. 149.2 +/- 5.1%) and incidence of ventricular arrhythmia during reperfusion (55.6 vs. 60.0%) compared to a control group. CO exposure alone increased the baseline coronary flow (20.1 +/- 1.5 vs. 12.8 +/- 0.6 ml/min/g) and the contracture magnitude (54.8 +/- 6.8 vs. 37.1 +/- 4.8%), improved both contractile recovery (66.1 +/- 6.3 vs. 30.8 +/- 7.5%) and ventricular arrhythmia incidence (22.2 vs. 60.0%), and increased the hyperemic coronary flow (26.7 +/- 1.5 vs. 19.1 +/- 0.7%). Preconditioning after CO exposure exacerbated ischemic contracture (shorter onset and higher magnitude), and increased the reactive hyperemia (29.8 +/- 1.4%), but raised the beneficial effects on contractile recovery (85.4 +/- 8.4%) without alteration of ventricular tachycardia prevention (22.2%). Thus, CO-exposed hearts could be preconditioned in the same way as normal myocardium.
Rochetaing
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A
Laboratoire de Préconditionnement et de Remodelage du Myocarde, UFR Sciences, 2 boulevard Lavoisier, F-49045 Angers Cedex, France. annie.rochetaing@univ-angers.fr
Barbé
C
C
Kreher
P
P
D000818:Animals; D002248:Carbon Monoxide / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000502:physiology; D019570:Inhalation Exposure; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009924:Organ Culture Techniques; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D017180:Tachycardia, Ventricular
D002248:Carbon Monoxide