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Articles in PresS, published online ahead of print May 16, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00549.2001
Submitted on June 25, 2001
Accepted on May 6, 2002
1 Pharmacology & Pediatrics, University of Alberta, Edmonton, Alberta, Canada
2 Biochemistry, University of Szeged, Szeged, Hungary
3 Cardiac Surgery, Ludwig-Maximillians University, Munich, Germany
* To whom correspondence should be addressed. E-mail: richard.schulz{at}ualberta.ca.
Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis but the actual species responsible remains unclear. We studied the alterations in myocardial NO, superoxide and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide-treated (LPS) rats. Six hours after LPS (4 mg/kg, i.p) or saline (control), hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 bpm. Cardiac work, O2 consumption and cardiac efficiency were markedly depressed in LPS hearts compared to controls. Plasma nitrate/nitrite level was elevated in LPS rats and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca2+-independent NOS activity and iNOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS hearts indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite occur in dysfunctional hearts from endotoxemic rats.
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