Acute, short-term hypercapnia improves microvascular oxygenation of the colon in an animal model of sepsis

Abstract

IntroductionThe deterioration of microcirculatory oxygenation of the gut plays a vital role in the development of sepsis. Acute hypercapnia enhances the microcirculatory oxygenation of the splanchnic region under physiological conditions, while the effect of hypercapnia under sepsis is unknown. The aim of this study was to investigate the effects of acute hypercapnia and hypercapnic acidosis on the colonic microcirculation and early cytokine response in polymicrobial sepsis. MethodsExperiments were performed on 103 male Wistar rats. Colon ascendens stent peritonitis (CASP) surgery with varying stent diameters was conducted to establish a moderate polymicrobial sepsis model. In a second series, 24h of sepsis development induced by CASP surgery was followed by 120min of volume-controlled and pressure-limited ventilation with either normocapnic (pCO2 45±5mmHg) or moderate hypercapnic ventilation targets (pCO2 75±5mmHg) via exogenous carbon dioxide application. The effect of acidosis was investigated by metabolically buffering the hypercapnic acidosis with tromethamine. Microcirculatory oxygenation of the colon wall (tissue reflectance spectrophotometry) and hemodynamic variables were recorded continuously and arterial blood gas and cytokine (TNF-α, IL-6, IL-10) levels were analyzed intermittently. ResultsIn septic animals the microcirculatory oxygenation of the colon deteriorated under normocapnia (−7.0±7.6% at 90min) but was maintained under hypercapnic acidosis (+3.6±7.6%) and buffered hypercapnia (+1.5±4.4%). Cytokine levels were significantly higher in septic animals as opposed to sham animals but did not differ between normocapnic and hypercapnic groups. ConclusionsAcute hypercapnic acidosis and buffered hypercapnia both improve splanchnic microcirculatory oxygenation in a septic animal model, thereby counteracting the adverse effect induced by sepsis. The circulating pro- and anti-inflammatory cytokine levels are not modulated after 120min of hypercapnia.