Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally invasive direct coronary artery bypass grafting

Objective: Unmodified reperfusion without cardioplegia in minimally invasiv e direct coronary artery bypass grafting procedures causes endothelial dysf unction that may predispose to polymorphonuclear neutrophil-mediated myocar dial injury. This study tested the hypothesis that ischemic preconditioning in a minimally invasive direct coronary artery bypass grafting model atten uates postischemic endothelial dysfunction in coronary vessels. Methods: In anesthetized dogs, the left anterior descending coronary artery was occlud ed for 30 minutes and reperfused for 3 hours without ischemic preconditioni ng (no-ischemic preconditioning; n = 7); in 7 dogs, the left anterior desce nding occlusion was preceded by 5 minutes occlusion followed by 5 minutes o f reperfusion, Relaxation responses to stimulators of nitric oxide synthase were used to evaluate endothelial function in arteries from the ischemic-r eperfused (left anterior descending) and nonischemic (left circumflex coron ary artery) zones, Results: Stimulated endothelial-dependent relaxation of epicardial left anterior descending artery to incremental concentrations of acetylcholine in the no-ischemic preconditioning animals was shifted to th e right, and maximal relaxation was attenuated compared with the nonischemi c left circumflex coronary artery (117% +/- 4% vs 138% +/- 5%), In contrast , acetylcholine-induced maximal relaxation was comparable in the left anter ior descending artery versus left circumflex coronary artery in the ischemi c preconditioning group (130% +/- 6% vs 135% +/- 5%), In 150- to 200-mu m l eft anterior descending microvessels, 50% relaxation occurred with a lower concentration (log[M]) of acetylcholine in ischemic preconditioning versus no-ischemic preconditioning (-8.0 +/- 0.4 vs -7.0 +/- 0.1) with no group di fferences in smooth muscle relaxation to sodium nitroprusside, suggesting e ndothelial-specific damage. Adherence of fluorescent labeled polymorphonucl ear neutrophils to epicardial coronary artery endothelium, used as an index of basal (unstimulated) anti-polymorphonuclear neutrophil function, was si gnificantly attenuated by ischemic preconditioning versus no-ischemic preco nditioning (293 +/- 25 polymorphonuclear neutrophils/mm(2) vs 528 +/- 29 po lymorphonuclear neutrophils/mm(2)). Conclusion: In this minimally invasive direct coronary artery bypass grafting model, both agonist-stimulated and b asal postischemic endothelial dysfunction were attenuated by ischemic preco nditioning.