title: Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses.
abstract: This study introduces the respiratory exchange ratio (RER; the ratio of whole-body CO2production to O2consumption) 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 CO2load 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.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil asteiner@usp.br.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Steiner
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Flatow
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Camila F
authors.initials: CF
authors.lastname: Brito
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Monique T
authors.initials: MT
authors.lastname: Fonseca
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Evilin N
authors.initials: EN
authors.lastname: Komegae
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012703:Serotyping; D012772:Shock, Septic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D008070:Lipopolysaccharides; D002245:Carbon Dioxide; D005947:Glucose
keywords: Acid buffering; glucose; hypothermia; inflammation; metabolism; respiratory exchange ratio; sepsis