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. He arts were then randomized to two groups: (1) a further 20-min aerobic perfu sion, and (2) ischemic preconditioning (2 cycles of 5 min of ischemia follo wed by 5 min of reperfusion). Hearts were then subjected to 25 min of low-f low (0.3 ml/min.) global ischemia (37 degreesC) 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 preconditi oning 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 r eperfusion (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 coronar y 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 beneficia l effects on contractile recovery (85.4 +/- 8.4%) without alteration of ven tricular tachycardia prevention (22.2%). Thus, CO-exposed hearts could be p reconditioned in the same way as normal myocardium.