C1‐Esterase‐Inhibitor Treatment at Early Reperfusion of Hemorrhagic Shock Reduces Mesentery Leukocyte Adhesion and Rolling

ABSTRACTObjective: Complement activation probably plays a pathogenic role in multiple organ failure in shock. This study evaluates the effects of C1‐esterase‐inhibitor treatment on leukocyte‐endothelial interaction in the mesenteric microcirculation in hemorrhagic shock.Methods: Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body wt. for 60 minutes) followed by a 4‐hour reperfusion period. C1‐INH (100 IU/kg body wt. i.v.) or 0.9% NaCl i.v. were administered as a bolus at the beginning of reperfusion. Reperfusion time mimicked a “pre‐hospital” phase of 30 minutes followed by a quasi “in‐hospital” phase of 3.5 hours. The “in‐hospital” phase was initiated by substitution of blood followed by fluid resuscitation with normal saline.Results: Application of C1‐INH markedly reduced rolling and adherent leukocytes to numbers approaching baseline values. Vmax and shear rate of the mesenteric microcirculation improved in both groups after reperfusion with a trend to higher values in the C1‐INH group (n.s.p= 0.08).Conclusion: C1‐INH applied in a bolus dose of 100 IU/kg body wt. i.v. abrogated enhanced leukocyte adhesion and rolling in the mesenteric microcirculation after hemorrhagic shock. Single bolus treatment with a complement inhibitor may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.