• Resuscitation · Jun 2010

    Comparative Study

    Plasma and myocardial visfatin expression changes are associated with therapeutic hypothermia protection during murine hemorrhagic shock/resuscitation.

    • David G Beiser, Huashan Wang, Jing Li, Xu Wang, Violeta Yordanova, Anshuman Das, Tamara Mirzapoiazova, Joe G N Garcia, Susan A Stern, and Terry L Vanden Hoek.
    • Section of Emergency Medicine, University of Chicago, Chicago, IL 60637, USA. dbeiser@uchicago.edu
    • Resuscitation. 2010 Jun 1;81(6):742-8.

    AimCytokine production during hemorrhagic shock (HS) could affect cardiac function during the hours after resuscitation. Visfatin is a recently described protein that functions both as a proinflammatory plasma cytokine and an intracellular enzyme within the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway. We developed a mouse model of HS to study the effect of therapeutic hypothermia (TH) on hemodynamic outcomes and associated plasma and tissue visfatin content.MethodsMice were bled and maintained at a mean arterial pressure (MAP) of 35 mmHg. After 30 min, animals (n=52) were randomized to normothermia (NT, 37+/-0.5 degrees C) or TH (33+/-0.5 degrees C) followed by rewarming at 60 min following resuscitation. After 90 min of HS (S90), mice were resuscitated and monitored for 180 min (R180). Visfatin, interleukin 6 (IL-6), keratinocyte-derived chemokine (KC), tumor necrosis factor-alpha (TNF-alpha), and myoglobin were measured by ELISA.ResultsCompared to NT, TH animals exhibited improved R180 survival (23/26 [88.5%] vs. 13/26 [50%]; p=0.001). Plasma visfatin, IL-6, KC, and TNF-alpha increased by S90 in both groups (p<0.05). TH attenuated S90 plasma visfatin and, after rewarming, decreased R180 plasma IL-6, KC, and myoglobin (p<0.05) relative to NT. Heart and gut KC increased at S90 while IL-6 increases were delayed until R180 (p<0.05). NT produced sustained elevations of myocardial KC but decreased visfatin by R180, effects abrogated by TH (p<0.05).ConclusionsIn a mouse model of HS, TH improves hemodynamics and alters plasma and tissue proinflammatory cytokines including the novel cytokine visfatin. TH modulation of cytokines may attenuate cardiac dysfunction following HS.Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

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