Inhibition of myocardial injury by ischemic postconditioning 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, 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, Deltaabsorbance.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/mm2) 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 (microM/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-con may be clinically applicable in coronary interventions, coronary artery bypass surgery, organ transplantation, and peripheral revascularization where reperfusion injury is expressed.
Zhao
Zhi-Qing
ZQ
Department of Cardiothoracic Surgery, The Carlyle Fraser Heart Center/Crawford Long Hospital, Emory University School of Medicine. 550 Peachtree Street NE, Atlanta, GA 30308-2225, USA. zzhao@emory.edu
Corvera
Joel S
JS
Halkos
Michael E
ME
Kerendi
Faraz
F
Wang
Ning-Ping
NP
Guyton
Robert A
RA
Vinten-Johansen
Jakob
J
D000818:Animals; D001794:Blood Pressure; D002448:Cell Adhesion / Q000276:immunology; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D004487:Edema / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D004996:Ethidium / Q000031:analogs & derivatives*; D005260:Female; D006339:Heart Rate; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology; D009504:Neutrophils / Q000166:cytology; D019007:P-Selectin / Q000032:analysis; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000032:analysis; D014664:Vasodilation; D017725:Ventricular Pressure
D019007:P-Selectin; C067883:dihydroethidium; D013481:Superoxides; D008315:Malondialdehyde; D009195:Peroxidase; D003402:Creatine Kinase; D004996:Ethidium