6533b871fe1ef96bd12d25a5

RESEARCH PRODUCT

C1-ESTERASE INHIBITOR REVERSES FUNCTIONAL CONSEQUENCES OF SUPERIOR MESENTERIC ARTERY ISCHEMIA/REPERFUSION BY LIMITING REPERFUSION INJURY AND RESTORING MICROCIRCULATORY PERFUSION

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description

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.Systemichemodynamicsweremonitoredcontinuously,arterial bloodgasesanalyzedintermittently, andleukocyte/ 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 perfusionto baseline levels in a dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to similar levels in both C1-INHYtreated 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. KEYWORDS—C1-esterase inhibitor, superior mesenteric artery, ischemia, bolus treatment, ileal lipid-binding protein, fatty acid-binding protein, intravital microscopy