Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial

Abstract

Introduction Sepsis impairs gastrointestinal microcirculation and it is hypothesized that this might increase patient’s mortality. Sub-therapeutic vasopressin improves gastric microcirculation under physiologic conditions whereas a therapeutic dosing regimen seems to be rather detrimental. However, the effects of sub-therapeutic vasopressin on gastrointestinal microcirculation in sepsis are largely unknown. Therefore, we conducted this trial to investigate the effect of sub-therapeutic as well as therapeutic vasopressin on gastrointestinal microcirculation in sepsis. Methods 40 male Wistar rats were randomized into 4 groups. Colon ascendens stent peritonitis (CASP)-surgery was performed to establish mild or moderate sepsis. 24 hours after surgery, animals received either vasopressin with increasing dosages every 30 min (6.75, 13.5 (sub-therapeutic), 27 mU · kg-1 · h-1 (therapeutic)) or vehicle. Microcirculatory oxygenation (μHBO2) of the colon was recorded for 90 min using tissue reflectance spectrophotometry. Intestinal microcirculatory perfusion (total vessel density (TVD; mm/mm2) and perfused vessel density (PVD; mm/mm2)) were measured using incident dark field-Imaging at baseline and after 60 min. Results In mild as well as in moderate septic animals with vehicle-infusion intestinal μHbO2, TVD and PVD remained constant. In contrast, in moderate sepsis, sub-therapeutic vasopressin with 13.5 mU · kg-1 · h-1 elevated intestinal μHBO2 (+ 6.1 ± 5.3%; p < 0.05 vs. baseline) and TVD (+ 5.2 ± 3.0 mm/mm2; p < 0.05 vs. baseline). μHBO2, TVD and PVD were significantly increased compared to moderate sepsis alone. However, therapeutic vasopressin did not change intestinal microcirculation. In mild septic animals sub-therapeutic as well as therapeutic vasopressin had no relevant effect on gastrointestinal microcirculation. Systemic blood pressure remained constant in all groups. Conclusion Sub-therapeutic vasopressin improves gastrointestinal microcirculatory oxygenation in moderate sepsis without altering systemic blood pressure. This protective effect seems to be mediated by an enhanced microcirculatory perfusion and thereby increased oxygen supply. In contrast, therapeutic vasopressin did not show this beneficial effect.