Role of nitric oxide in cardiovascular response to endotoxemia in neonatal lambs

Jay M Milstein, E. Milano, B. W. Goetzman, S. H. Bennett

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Infection in the human infant remains a major cause of mortality with their deaths being characterized by cardiovascular collapse. In a previous study in our laboratory, we found that neonatal lambs exposed to endotoxin consistently developed hypotension with 44% developing depressed left ventricular contractility. The purpose of the present study was to establish whether these effects are mediated by nitric oxide. We evaluated the effects of Escherichia coli endotoxin (0.5 mg/kg) on time dependent changes in left ventricular contractility and standard hemodynamics in a neonatal sheep model treated with nitric oxide synthase inhibition with Nω-nitro-L-arginine methyl ester, L-NAME. We studied 23 acutely anesthetized 0-3 day old lambs which were divided into four groups: Control, C; endotoxin, E; endotoxin + L-NAME where L-NAME was given prior to endotoxin, ELN; and control + L-NAME, CLN. Contractility, measured as end-systolic elastance, Ees, increased transiently in the E group (E>C)*(a finding which was not present in our previous study) and then returned to baseline. In contrast, Ees declined over time in the ELN group (ELN<C)* & (ELN<E)*. In terms of peripheral hemodynamics, both the E and ELN groups demonstrated significant progressive decreases in mean arterial blood pressure and systemic vascular resistance (E<C)* & (ELN<C)*. The results of this study suggest that nitric oxide contributes to the neonatal contractile response of the heart to endotoxin and does not appear to mediate the systemic vascular relaxation response, however, because of the variable finding of a hyperdynamic phase in the current E group in contrast to its matching group in our previous study, we conclude that other factors such as preconditioning with prior perinatal exposure to endotoxin may be invoked.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Issue number2
StatePublished - Feb 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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