Page 1- R1 Inhibition of myocardial injury by ischemic post-conditioning during reperfusion: comparison with ischemic preconditioning

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 (R), i.e. post-conditioning (Post-con), is cardioprotective by attenuating R injury. In anesthetized open-chest dogs, the LAD was occluded for 60 min and reperfused for 3 h. In Controls (Con, 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 R, 3 cycles of 30 s R and 30 s LAD re-occlusion preceded the 3 h of R. Infarct size was significantly less in the Pre-con (15±2%*) and Post-con (14±2%*) groups compared to Con (25±3%). Tissue edema (% water content) in the area at risk was comparably reduced in Pre-con (78.3±1.2*) and Post-con (79.7±0.6*) vs. Con (81.5±0.4). Neutrophil (PMN) accumulation (myeloperoxidase activity, abs/min/g tissue) in the area at risk myocardium was comparably reduced in Post-con (10.8±5.5*) and Pre-con (13.4±3.4*) vs. Con (47.4±15.3). Basal endothelial function measured by PMN adherence to post-ischemic LAD endothelium (PMNs/mm) was comparably attenuated by Post-con and Pre-con (15±0.6* and 12±0.6*) vs. Con (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 post-ischemic LAD to acetylcholine, was significantly greater in Postcon (104±6%*) and Pre-con (109±5%*) vs. Con (71±8%). Plasma malonaldehyde (μM/ml), a product of lipid peroxidation, was significantly less at 1 h of R in Post-con (2.2±0.2*) vs. Con (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-con may be clinically applicable in coronary interventions, coronary artery bypass surgery, organ transplantation and peripheral revascularization where reperfusion injury is expressed. * P<0.05 Post-con and Pre-con vs. Con.