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 CO 2 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 CO 2 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.

Interplay between brain oxygenation and the development of hypothermia in endotoxic shock

“…Such a rise in RER has been shown to reflect metabolic acidosis resultant from the activation of glycolysis, independently of the suppression of aerobic metabolism (14). These characteristics match those of the thermal and metabolic responses to a high dose of LPS in studies involving less complex surgical preparations (9,14,15), which implies that the complexity of the surgical preparation employed in the present study did not exert undesired effects on the responses of interest. Furthermore, none of the physiological parameters monitored were affected in rats injected with pyrogen-free saline (Fig.…”

Increased lipopolysaccharide‐induced hypothermia in neurogenic hypertension is caused by reduced hypothalamic PGE2 production and increased heat loss

“…A recent study has suggested that H + increased production observed during the early phase of endotoxic shock correlates with RER (Steiner et al . 2017a). Acute rises in RER were observed consistently after LPS administration in Wistar rats (Fig.…”

Diet-induced obesity attenuates the hypothermic response to lipopolysaccharide independently of TNF-α production

“…Early on the day of the experiment, the freely moving rats were transferred individually caged to an environmental chamber (NQ1 model; Environmental Growth Chambers, Chagrin Falls, OH, USA). In the chamber, the rats were maintained at an ambient temperature of 22.0ºC, which is preferred by rats challenged with high doses of LPS [25][26][27] and adequate to reveal the hypothermic component of the response to LPS [28][29][30]. Each cage was placed on top of a PhysiolTel RPC-1 receiver (Data Sciences), which captured the radio waves emitted by the telemetry transmitter, and conveyed temperature and locomotor activity data to a computer.…”