title: Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning.
abstract: Ischemic postconditioning (IPOC) could be ineffective or even detrimental if the index ischemic duration is either too short or too long. The present study is to demonstrate that oxygen supply and metabolism defines a salvageable ischemic time window of IPOC in mice. C57BL/6 mice underwent coronary artery occlusion followed by reperfusion (I/R), with or without IPOC by three cycles of 10 s/10 s R/I. In vivo myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Regional blood flow (RBF) was measured with a laser Doppler monitor. At the end of 60 min reperfusion, tissue from the risk area was collected, and mitochondrial enzyme activities were assayed. Tissue oximetry demonstrated that I/R induced a reperfusion hyperoxygenation state in the 30- and 45-min but not 15- and 60-min ischemia groups. IPOC attenuated the hyperoxygenation with 45 but not 30 min ischemia. RBF, eNOS phosphorylation, and mitochondrial enzyme activities were suppressed after I/R with different ischemic time, and IPOC afforded protection with 30 and 45 but not 60 min ischemia. Infarct size measurement indicated that IPOC reduced infarction with 30 and 45 min but not 60 min ischemia. Clearly, IPOC protected mouse heart with a defined ischemic time window between 30 and 45 min. This salvageable time window was accompanied by the improvement of RBF due to increased phosphorylated eNOS and the preservation of mitochondrial oxygen consumption due to conserved mitochondrial enzyme activities. Interestingly, this salvageable ischemic time window was mirrored by tissue hyperoxygenation status in the postischemic heart.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, The Center for Biomedical Electron Paramagnetic Resonance Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Columbus, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Yuanjing
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Harold M
authors.initials: HM
authors.lastname: Swartz
authors.forename: Chwen-Lih
authors.initials: CL
authors.lastname: Chen
authors.forename: Yeong-Renn
authors.initials: YR
authors.lastname: Chen
authors.forename: Guanglong
authors.initials: G
authors.lastname: He
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D054059:Coronary Occlusion / Q000503:physiopathology; D057775:Ischemic Postconditioning; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000201:enzymology; D009203:Myocardial Infarction / Q000201:enzymology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*
chemical_list: D052250:Nitric Oxide Synthase Type III