title: C1-esterase inhibitor reverses functional consequences of superior mesenteric artery ischemia/reperfusion by limiting reperfusion injury and restoring microcirculatory perfusion.
abstract: Activated complement contributes significantly to reperfusion injury after ischemia. This study explores functional consequences of C1-esterase inhibitor (C1-INH) treatment after superior mesenteric artery occlusion (SMAO)/reperfusion using intravital microscopy. Thirty anesthetized, spontaneously breathing, male Sprague-Dawley rats underwent SMAO for 60 min followed by reperfusion (4 h). C1-esterase inhibitor (100 and 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 determined from serum samples with an enzyme-linked immunosorbent assay at the end of the experiments. C1-esterase inhibitor restored microcirculatory perfusion to baseline levels in a dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1-INH treatment efficiently prevented metabolic acidosis, reduced the need for intravenous fluids to support blood pressure, and decreased I-LBP levels in a dose-dependent manner. 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. C1-esterase inhibitor bolus infusion efficiently blunted functional consequences of mesenteric ischemia/reperfusion with I-LBP, proving to be a valuable serum marker mirroring the effect of ischemia/reperfusion and treatment at the end of the experiments.
authors.affiliation: Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University Mainz, Germany. mlauterbach@rics.bwh.harvard.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Lauterbach
authors.forename: Georg
authors.initials: G
authors.lastname: Horstick
authors.forename: Nicola
authors.initials: N
authors.lastname: Plum
authors.forename: Johannes
authors.initials: J
authors.lastname: Lotz
authors.forename: Enise
authors.initials: E
authors.lastname: Lauterbach
authors.forename: Ludwig S
authors.initials: LS
authors.lastname: Weilemann
authors.forename: Oliver
authors.initials: O
authors.lastname: Kempski
mesh_terms: D000818:Animals; D050718:Complement C1 Inhibitor Protein / Q000502:physiology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000601:surgery*; D008833:Microcirculation / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D050718:Complement C1 Inhibitor Protein