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Effect of C1-esterase inhibitor treatment on microcirculatory perfusion after superior mesenteric artery ischemia

Multiple studies have stressed the importance of the contribution of activated complement to the pathology of reperfusion injury after tissue ischemia. Using intravital microscopy, this study explores functional consequences of the inhibition of the classical pathway of complement activation with C1-esterase inhibitor (C1-INH) in the context of superior mesenteric artery occlusion (SMAO)/reperfusion.

Thirty anesthetized, spontaneously breathing, male Sprague–Dawley rats underwent SMAO for 60 minutes followed by reperfusion (4 hours). C1-esterase inhibitor (100 IU/kg, 200 IU/kg body weight) or saline (0.9%) was given as a single bolus before reperfusion. Sham-operated animals (n = 10) without SMAO served as controls. Systemic hemodynamics were monitored continuously, arterial blood gases analyzed intermittently, and leukocyte/endothelial interactions in the mesenteric microcirculation quantified at intervals using intravital microscopy. Ileal lipid-binding protein (I-LBP) levels were measured from serum samples with an ELISA at the end of the experiments.

C1-INH restored microcirculatory perfusion of postcapillary venules to baseline levels in a dose-dependent manner and reduced leukocyte adhesion following SMAO/reperfusion to similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1-INH treatment efficiently prevented metabolic acidosis, and reduced the need for intravenous fluids to support blood pressure. Furthermore, I-LBP levels decreased in a dose-dependent manner, and were comparable with the levels of sham-operated animals at the end of the experiments. Survival rates were 100% in controls and after 200 IU/kg C1-INH, 90% after 100 IU/kg C1-INH, and 30% in saline-treated animals.

In the setting of mesenteric ischemia, C1-INH given as a bolus infusion shortly before reperfusion efficiently restored microcirculatory perfusion in a dose-dependent manner, reduced local and systemic inflammatory response, and improved outcome. I-LBP levels correlated well with the functional consequences of mesenteric ischemia/reperfusion and treatment at the end of the experiments.

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Lauterbach, M., Horstick, G., Plum, N. et al. Effect of C1-esterase inhibitor treatment on microcirculatory perfusion after superior mesenteric artery ischemia. Crit Care 11, P30 (2007). https://doi.org/10.1186/cc5190

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Keywords

  • Ileal
  • Metabolic Acidosis
  • Mesenteric Ischemia
  • Classical Pathway
  • Single Bolus