Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. ⋯ Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.
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Deletion of the cellular inhibitor of apoptosis protein 2 (cIAP2) is capable of rendering lipopolysaccharide (LPS)-activated macrophages highly susceptible to apoptotic triggers, thereby quickly eliminating the resident macrophage population soon after the initiation of a systemic inflammatory response. The aim of our study was to evaluate the impact of cIAP2 deletion on leukocyte recruitment and capillary perfusion in experimental endotoxemia and polybacterial sepsis using intravital microscopy of the intestinal microcirculation, which is crucial in the pathogenesis of septic multiple organ failure. We studied six groups of animals: wild-type (WT) control mice, cIAP2 knockout mice, endotoxemic WT mice (5 mg/kg LPS), endotoxemic cIAP2 knockouts (5 or 50 mg/kg LPS, respectively), and WT as well as knockout mice with polybacterial sepsis (colon ascendens stent peritonitis [CASP]). ⋯ Lipopolysaccharide-induced decrease in intestinal microvascular blood flow was not affected by cIAP2 inhibition. In CASP-induced sepsis, cIAP2 deletion had no effect on intestinal leukocyte recruitment. Deletion of cIAP2 resulted in reduced microvascular leukocyte recruitment within the intestinal microcirculation in endotoxemia but not in polybacterial sepsis.