Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses. Issue 1 (13th January 2017)

• Record Type: Journal Article
• Authors: Steiner, Alexandre A.; Flatow, Elizabeth A.; Brito, Camila F.; Fonseca, Monique T.; Komegae, Evilin N.
• Is Part Of: Physiological reports. Volume 5:Issue 1(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-01-13
• Subjects: Acid buffering -- glucose -- hypothermia -- inflammation -- metabolism -- respiratory exchange ratio -- sepsis; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13100
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: This study introduces the respiratory exchange ratio (RER; the ratio of whole‐body CO2 production to O2 consumption) as an aid to monitor metabolic acidosis during the early phase of endotoxic shock in unanesthetized, freely moving rats. Two serotypes of lipopolysaccharide (lipopolysaccharide [LPS] O55:B5 and O127:B8) were tested at shock‐inducing doses (0.5–2 mg/kg). Phasic rises in RER were observed consistently across LPS serotypes and doses. The RER rise often exceeded the ceiling of the quotient for oxidative metabolism, and was mirrored by depletion of arterial bicarbonate and decreases in pH. It occurred independently of ventilatory adjustments. These data indicate that the rise in RER results from a nonmetabolic CO2 load produced via an acid‐induced equilibrium shift in the bicarbonate buffer. Having validated this new experimental aid, we asked whether acidosis was interconnected with the metabolic and thermal responses that accompany endotoxic shock in unanesthetized rats. Contrary to this hypothesis, however, acidosis persisted regardless of whether the ambient temperature favored or prevented downregulation of mitochondrial oxidation and regulated hypothermia. We then asked whether the substrate that fuels aerobic metabolism could be a relevant factor in LPS‐induced acidosis. Food deprivation was employed to divert metabolism away from glucose oxidation and toward fatty acid oxidation. Interestingly, this intervention attenuated the RER response to LPS by 58%, without suppressing other key aspects of systemic inflammation. We conclude that acid production in unanesthetized rats with endotoxic shock results from a phasic activation of glycolysis, which occurs independently of physiological changes in mitochondrial oxidation and body temperature. Abstract : Although acidosis is considered a key aspect of septic and endotoxic shock, the available data lack temporal resolution and stem mainly from anesthetized animals with an artificially constant body temperature. Here, we validated the respiratory exchange ratio as an aid to noninvasively trace the course of acidosis in unanesthetized rats with endotoxic shock, then used this tool to evaluate the relationship of acidosis with metabolic fuel substrates and thermometabolic responses.