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Am J Physiol Regul Integr Comp Physiol 293: R1893-R1897, 2007. First published August 22, 2007; doi:10.1152/ajpregu.00359.2007
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TRANSLATIONAL PHYSIOLOGY

Right ventricular TNF resistance during endotoxemia: the differential effects on ventricular function

Troy A. Markel,1 Paul R. Crisostomo,1 Meijing Wang,1 Jeremy L. Herrmann,1 Aaron M. Abarbanell,1 and Daniel R. Meldrum1,2,3

Departments of Surgery,1 Cellular and Integrative Physiology,2 and The Center for Immunobiology,3 Indiana University School of Medicine, Indianapolis, Indiana

Submitted 21 May 2007 ; accepted in final form 13 August 2007

ABSTRACT

Right and left ventricular myocytes originate from different cellular progenitors; however, it is unknown whether these cells differ in their response to endotoxemia. We hypothesized that 1) the percentage of endotoxemic functional depression within the right ventricle (RV) would be smaller than that of the left ventricle; and 2) that better RV function would correlate with lower levels of right ventricular TNF production. Adult Sprague-Dawley rats were divided into right and left control and endotoxin groups. Controls received vehicle, while endotoxin groups received LPS at 20 mg/kg ip. Hearts were excised either 2 or 6 h after injection. Hearts excised at 2 h were assayed for TNF, IL-6, TNF receptor 1 (TNFR1), TNFR2, and via ELISA, while hearts excised at 6 h were assayed via the Langendorff model. The percentage of cardiac functional depression, exhibited as developed pressure, contractility, and rate of relaxation (expressed as a percentage of control) was significantly smaller in right ventricles compared with left ventricles following endotoxin exposure. Tissue levels of TNF were significantly elevated in both right and left ventricles 2 h after endotoxin exposure, and right ventricular endotoxin groups expressed higher levels of TNF compared with their left ventricular counterparts. No significant differences in IL-6, TNFR1, or TNFR2 levels were noted between endotoxin-exposed ventricles. This is the first study to demonstrate that right and left ventricular function differs after endotoxin exposure.

sepsis; cardiac; IL-6; cardiovascular collapse



Address for reprint requests and other correspondence: D. R. Meldrum, 545 Barnhill Dr., Emerson Hall 215, Indianapolis, IN 46202 (e-mail: dmeldrum{at}iupui.edu)




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Am J Physiol Cell Physiol, March 1, 2008; 294(3): C675 - C682.
[Abstract] [Full Text] [PDF]




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