title: Cardiac UCP2 expression and myocardial oxidative metabolism during acute septic shock in the rat.
abstract: Septic shock decreases cardiac hydraulic work relative to the rate of myocardial oxygen consumption, causing decreased mechanical efficiency (hydraulic work/myocardial oxygen consumption). This study tested whether the mitochondrial uncoupling protein UCP2 was responsible for decreased cardiac mechanical efficiency after polymicrobial septic shock. Sepsis was initiated in ketamine/xylazine-anesthetized rats by cecal ligation and puncture (CLP). Steady-state mRNA content was quantified by Northern blot analysis, and protein content was estimated by western blot. Additional hearts were removed after 12 h and perfused in working mode to measure work (mmHg x mL/min/100 g dry wt) and efficiency (CE = work/oxygen consumption, %). The 72-h mortality rate was 80%, and deaths occurred between 12-32 h. Cardiac work (152 +/- 15, shock vs. 235 +/- 16, control; P < 0.05) and cardiac efficiency (4.0 +/- 0.4 vs. 5.6 +/- 0.3; P < 0.05) were significantly decreased when hearts were isolated 12 h after CLP. Myocardial UCP2 mRNA expression was increased by 52% (12 h) compared with control hearts; however, there was no detectable UCP2 protein in mitochondria isolated from either control or septic hearts.
  
  
  CONCLUSIONS
  Although polymicrobial sepsis decreased cardiac mechanical efficiency and increased UCP-2 expression coincident with premortal hypothermia, we did not detect any evidence of UCP-2 protein in septic heart muscle. These data argue against the hypothesis that UCP-2 causes decreased cardiac mechanical efficiency in septic shock.
authors.affiliation: Division of Research, Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina 28323-2861, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roshon
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kline
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Thornton
authors.forename: John A
authors.initials: JA
authors.lastname: Watts
mesh_terms: D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D002432:Cecum / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D015342:DNA Probes; D018076:DNA, Complementary; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D007473:Ion Channels; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016019:Survival Analysis; D000071246:Uncoupling Protein 2
chemical_list: D015342:DNA Probes; D018076:DNA, Complementary; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D009195:Peroxidase