Milrinone and Levosimendan Improve Microvascular Perfusion in Septic Rats: A Randomised, Placebo-Controlled Trial

Authors: Carsten Marcus, Stefan Hof, Alena Gesing, Philisa Thelen, Sarah Orzol, Antonia Vocke, Jan Schulz, Anne Konstanze Charlotte Kuebart, Richard Truse, Christian Vollmer, Inge Bauer, Olaf Picker, and Anna Herminghaus

Microcirculatory dysfunction is a central feature of sepsis, contributing to gastrointestinal barrier impairment, systemic inflammation, and organ failure. This study evaluated the effects of milrinone and levosimendan, alone and in combination with low-dose vasopressin, on colonic and hepatic microcirculation and mitochondrial respiration in a rat model of abdominal sepsis induced by colon ascendens stent peritonitis. Microvascular blood flow and oxygenation were measured using spectrophotometry and laser Doppler flowmetry, while mitochondrial function was assessed by respirometry.

In septic animals, both milrinone and levosimendan increased colonic and hepatic microvascular blood flow without affecting microvascular oxygenation or mitochondrial respiration. The addition of vasopressin maintained the increase in colonic perfusion but attenuated the hepatic microcirculatory response. No significant differences were observed in sham-operated animals. These findings indicate that inotropic agents enhance regional microvascular blood flow in abdominal sepsis, while adjunctive vasopressin exerts differential, organ-specific effects without altering mitochondrial function.