Abstract
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.
Highlights
To clarify the relation between ATP and prostaglandinE2 (PGE2) in the immunologic system, we investigated the acute and chronic effects of PGE2 on activation of purinergic signaling in monocytes by measuring the ATP-induced elevation of intracellularCa2+ ([Ca]i) in fura-2-loaded THP-1 monocytes
IFNγ plays a critical role in host defense by promoting Th1 phenotype and bacterial clearance
Low IFNγ levels are were washed, loaded with fura-2-AM, and transferred into a quartz associated with the Th2 phenotype consistent with critical illness cuvette and placed in the thermostat-regulated sample chamber of anergy [2]
Summary
To clarify the relation between ATP and prostaglandinE2 (PGE2) in the immunologic system, we investigated the acute and chronic effects of PGE2 on activation of purinergic signaling in monocytes by measuring the ATP-induced elevation of intracellularCa2+ ([Ca]i) in fura-2-loaded THP-1 monocytes. Several experimental studies suggest that thrombolysis therapy acts directly on thrombi or emboli and enhances microcirculatory reperfusion In this retrospective study we investigated the extent of blood coagulation and fibrin formation via the plasma D-dimer level, an indicator of endogenous fibrinolytic activity, in patients who underwent inhospital and out-of-hospital cardiac arrest from nontraumatic causes. Methods MEDLINE, EMBASE, CINAHL, and the Cochrane Library were searched, and studies were included if they reported on ICU patients > 16 years old who were evaluated for CINMA clinically and electrophysiologically, and they contained sufficient data to quantitatively measure the association between CINMA and clinically relevant exposures and/or outcomes. Our aim was to evaluate the role of the cardiac markers NT-proBNP, Troponin T (TnT) and myoglobin as predictors of inhospital and 6-month all-cause mortality in patients admitted to a general adult ICU with severe sepsis/septic shock. Aging is associated with decreased cardiopulmonary and renal reserve as well as the development of progressive organ failure
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