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.
|Original language||English (US)|
|Number of pages||7|
|Journal||Shock (Augusta, Ga.)|
|State||Published - Jun 2003|
ASJC Scopus subject areas
- Emergency Medicine
- Critical Care and Intensive Care Medicine