Background: Sepsis is a life-threatening condition with systemic inflammation and microcirculatory dysfunction, leading to multi organ dysfunction syndrome. Gastrointestinal microcirculatory impairment and mitochondrial dysfunction play a crucial role in sepsis progression by disturbing mucosal barrier integrity, leading to bacterial translocation, and exacerbating systemic inflammation. While dobutamine is commonly used to support cardiac output, its direct effects on intestinal microcirculation and mitochondrial respiration remain unclear. A similar uncertainty exists for addition of low-dose vasopressin, a second-line vasoconstrictor in septic shock. Objective: This study aimed to investigate the effects of dobutamine and sub-therapeutic vasopressin on colonic microcirculation and mitochondrial function in a rat model of abdominal sepsis. Methods: 24 h after induction of sepsis (colon ascendens stent peritonitis, CASP) or sham surgery, male Wistar rats (n = 88) were randomized into eight groups: control (crystalloid vehicle), vasopressin, dobutamine, and a combination of both drugs either in the sepsis or in the sham group. Microcirculatory variables, including oxygenation (µHbO₂) and blood flow (µFlow), were assessed in colon and liver using tissue-reflectance spectrophotometry and laser Doppler flowmetry, respectively for 90 min. Mitochondrial function was assessed in colon and liver homogenates of septic animals via respirometry. Statistical analysis: Mixed effects model followed by Tukey’s and Dunnett’s post-hoc tests and Kruskal-Wallis test for mitochondrial respirometry (significance level p < 0.05). Data are expressed as mean ± SD for microcirculatory data and Min/Median/Max for mitochondrial data. Results: Dobutamine significantly improved colonic microvascular oxygenation (∆µHbO₂: 10.2 ± 13.4 % vs. control -2.3 ± 4.4 % and vs. baseline, p < 0.05) and blood flow (∆Flow 30 ± 20 AU vs baseline, p < 0.05) in septic rats after 60 minutes. The combination of dobutamine and vasopressin in sepsis enhanced microcirculatory blood flow (∆Flow 28 ± 27 AU vs. baseline p < 0.05) but did not increase tissue oxygenation. Hepatic microcirculation and mitochondrial respiration remained widely unaltered across all groups. Conclusions: Dobutamine improves colonic microcirculation in sepsis by improving oxygenation and flow. The combination with vasopressin abolishes the effects of dobutamine on tissue oxygenation in septic rats. These findings suggest a potential role of dobutamine in mitigating sepsis-induced microcirculatory failure.
Marcus et al. (Tue,) studied this question.