title: Remote ischemic preconditioning mitigates myocardial and neurological dysfunction via K(ATP) channel activation in a rat model of hemorrhagic shock.
abstract: Severe hemorrhagic shock and resuscitation is a state of global body ischemia and reperfusion that causes myocardial and cerebral dysfunction. We investigated whether remote ischemic preconditioning (RIPC) would reduce myocardial and cerebral ischemia and reperfusion injuries after hemorrhagic shock as the result of the K(ATP) channel activation. Twenty-one male rats were randomized into three groups: RIPC, RIPC with K(ATP) channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by reperfusion for 5 min. Hemorrhagic shock was induced by removing 50% of the estimated total blood volume during an interval of 1 h. Thirty minutes after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The animals were monitored for 2 h and observed for an additional 72 h. Myocardial function was measured by echocardiography, and sublingual microcirculation was measured by a sidestream dark-field imaging device at baseline, 1 h after bleeding, 30 min after the completion of bleeding, 30 min after reinfusion, and hourly intervals thereafter. The survival and neurological function were evaluated at 12, 24, 48, and 72 h after reinfusion. At 2 h after reinfusion, ejection fraction and myocardial performance index were significantly better in the RIPC group than in the control group (P < 0.01). The sublingual microvascular flow index and perfused vessel density were significantly greater after reinfusion in the RIPC group than that in the control group (P < 0.01). The duration of survival was significantly longer, and neurological deficit score was significantly better in the RIPC group than the control animals (P < 0.01). Pretreatment with the K(ATP) channel blocker (glibenclamide) completely abolished the myocardial and cerebral protective effects of RIPC. We demonstrate, for the first time, that after severe hemorrhagic shock and resuscitation, RIPC mitigated myocardial and neurological dysfunction with improved survival by activation of the K(ATP) channel.
authors.affiliation: *Weil Institute of Critical Care Medicine, Rancho Mirage, California; †The Second Hospital of Anhui Medical University, Hefei, China; and ‡Keck School of Medicine of the University of Southern California, Los Angeles, California.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Hu
authors.forename: Zhengfei
authors.initials: Z
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Qian
authors.forename: Jena
authors.initials: J
authors.lastname: Cahoon
authors.forename: Jiefeng
authors.initials: J
authors.lastname: Xu
authors.forename: Shijie
authors.initials: S
authors.lastname: Sun
authors.forename: Wanchun
authors.initials: W
authors.lastname: Tang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply*; D006439:Hemodynamics; D019194:Ischemic Preconditioning / Q000379:methods*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D013318:Stroke Volume; D013997:Time Factors; D014059:Tongue / Q000098:blood supply*; D016277:Ventricular Function, Left
chemical_list: D054086:KATP Channels; D026902:Potassium Channel Blockers