Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning

Department of Cardiothoracic Surgery, The Carlyle Fraser Heart Center/Crawford Long Hospital, Emory University School of Medicine, Atlanta, Georgia 30308-2225 Submitted 9 December 2002 ; accepted in final form 27 March 2003 Ischemic preconditioning (Pre-con) is an adaptive response triggered by a brief ischemia applied before a prolonged coronary occlusion. We tested the hypothesis that repetitive ischemia applied during early reperfusion, i.e., postconditioning (Post-con), is cardio-protective by attenuating reperfusion injury. In anesthetized open-chest dogs, the left anterior descending artery (LAD) was occluded for 60 min and reperfused for 3 h. In controls ( n = 10), there was no intervention. In Pre-con ( n = 9), the LAD was occluded for 5 min and reperfused for 10 min before the prolonged occlusion. In Post-con ( n = 10), at the start of reperfusion, three cycles of 30-s reperfusion and 30-s LAD reocclusion preceded the 3 h of reperfusion. Infarct size was significantly less in the Pre-con (15 ± 2%, P < 0.05) and Post-con (14 ± 2%, P < 0.05) groups compared with controls (25 ± 3%). Tissue edema (% water content) in the area at risk was comparably reduced in Pre-con (78.3 ± 1.2, P < 0.05) and Post-con (79.7 ± 0.6, P < 0.05) versus controls (81.5 ± 0.4). Polymorphonuclear neutrophil (PMN) accumulation (myeloperoxidase activity, absorbance·min – 1 ·g tissue – 1 ) in the area at risk myocardium was comparably reduced in Post-con (10.8 ± 5.5, P < 0.05) and Pre-con (13.4 ± 3.4, P < 0.05) versus controls (47.4 ± 15.3). Basal endothelial function measured by PMN adherence to postischemic LAD endothelium (PMNs/mm 2 ) was comparably attenuated by Post-con and Pre-con (15 ± 0.6 and 12 ± 0.6, P < 0.05) versus controls (37 ± 1.5), consistent with reduced expression of P-selectin on coronary vascular endothelium in Post-con and Pre-con. Endothelial function assessed by the maximal vasodilator response of postischemic LAD to acetylcholine was significantly greater in Post-con (104 ± 6%, P < 0.05) and Pre-con (109 ± 5%, P < 0.05) versus controls (71 ± 8%). Plasma malondialdehyde (µM/ml), a product of lipid peroxidation, was significantly less at 1 h of reperfusion in Post-con (2.2 ± 0.2, P < 0.05) versus controls (3.2 ± 0.3) associated with a decrease in superoxide levels revealed by dihydroethidium staining in the myocardial area at risk. These data suggest that Post-con is as effective as Pre-con in reducing infarct size and preserving endothelial function. Post-