Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia

Author(s)

Corrigan, Joshua J. ^{[1, 2]} ; Fonseca, Monique T. ^[3] ; Flatow, Elizabeth A. ^[3] ; Lewis, Kevin ^[1] ; Steiner, Alexandre A. ^{[3, 1, 2]}

Affiliation

^[1] Albany Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Albany, NY - USA

^[2] St Josephs Hosp, Phoenix, AZ - USA

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 592, n. 17, p. 3901-3916, SEP 1 2014.
• Web of Science Citations: 13

Abstract

We tested the hypothesis that development of hypothermia instead of fever in endotoxic shock is consequential to hypoxia. Endotoxic shock was induced by bacterial lipopolysaccharide (LPS, 500gkg(-1) i.v.) in rats at an ambient temperature of 22 degrees C. A (3)-adrenergic agonist known to activate metabolic heat production, CL316,243, was employed to evaluate whether thermogenic capacity could be impaired by the fall in oxygen delivery (D.O2) during endotoxic shock. This possibility was rejected as CL316,243 (0.15mgkg(-1) i.v.) evoked similar rises in oxygen consumption (V.O2) in the presence and absence of endotoxic shock. Next, to investigate whether a less severe form of circulatory hypoxia could be triggering hypothermia, the circulating volume of LPS-injected rats was expanded using 6% hetastarch with the intention of improving tissue perfusion and alleviating hypoxia. This intervention attenuated not only the fall in arterial pressure induced by LPS, but also the associated falls in V.O2 and body temperature. These effects, however, occurred independently of hypoxia, as they were not accompanied by any detectable changes in NAD(+)/NADH ratios. Further experimentation revealed that even the earliest drops in cardiac output and D.O2 during endotoxic shock did not precede the reduction in V.O2 that brings about hypothermia. In fact, DO2 and VO2 fell in such a synchrony that the DO2/VO2 ratio remained unaffected. Only when hypothermia was prevented by exposure to a warm environment (30 degrees C) did an imbalance in the DO2/VO2 ratio become evident, and such an imbalance was associated with reductions in the renal and hypothalamic NAD(+)/NADH ratios. In conclusion, hypometabolism and hypothermia in endotoxic shock are not consequential to hypoxia but serve as a pre-emptive strategy to avoid hypoxia in this model. (AU)

• FAPESP's process: 12/03831-8 - Linking energy balance to systemic inflammation: role of leptin
• Grantee: Alexandre Alarcon Steiner
• Support type: Research Grants - Young Investigators Grants