Abstract
BACKGROUND: Sepsis is characterized by systemic inflammation and microcirculatory dysfunction, contributing to multiorgan failure. In the gastrointestinal tract, impaired microcirculation and mitochondrial dysfunction promote barrier failure and bacterial translocation. While dobutamine is commonly used to augment cardiac output in septic shock, its direct effects on intestinal microcirculation and mitochondrial respiration remain unclear. The microcirculatory impact of adjunctive low-dose vasopressin is similarly uncertain. METHODS: Twenty-four hours after colon ascendens stent peritonitis or sham surgery, 88 male Wistar rats were randomized to receive vehicle, vasopressin, dobutamine, or their combination under septic or sham conditions. Colonic and hepatic microcirculatory oxygenation (µHbO 2 ) and microvascular blood flow (µFlow) were measured for 90 minutes using tissue-reflectance spectrophotometry and laser Doppler flowmetry. Mitochondrial respiration was assessed in colon and liver homogenates of septic animals by high-resolution respirometry. Microcirculatory data were analyzed using mixed-effects models with Tukey's and Dunnett's post hoc tests. Mitochondrial data were analyzed using the Kruskal-Wallis test. A two-sided P < 0.05 was considered statistically significant. RESULTS: In septic rats, dobutamine significantly improved colonic microvascular oxygenation (∆µHbO 2 10.2% ± 13.4% vs. -2.3% ± 4.4% in controls and vs. baseline, P < 0.05) and microvascular blood flow (∆µFlow 30 ± 20 arbitrary units vs. baseline, P < 0.05). Combined dobutamine and vasopressin increased microvascular blood flow (∆µFlow 28 ± 27 arbitrary units vs. baseline, P < 0.05) but did not improve tissue oxygenation. Hepatic microcirculation and mitochondrial respiration remained largely unaltered. CONCLUSIONS: Dobutamine improves colonic microcirculation in sepsis, whereas concomitant vasopressin attenuates its oxygenation effects.