The Journal of surgical research
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Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokine release from activated macrophages. The aim of this study was to determine if IL-10 would decrease serum cytokine elevation in a murine model of cecal ligation and puncture (CLP). ⋯ Prophylactic or therapeutic administration of IL-10 significantly attenuated this early rise in serum cytokines. These results support the hypothesis that (1) CLP produces an early systemic rise in macrophage-derived cytokines and (2) IL-10 given either before or after the onset of CLP-induced intraabdominal infection and sepsis is able to inhibit this early release of macrophage-derived systemic mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis.
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Recent studies indicate that polymicrobial sepsis can markedly increase inducible macrophage Ao (nonnecrotic cellular suicide) and that this is associated with decreased M phi function. In vitro studies suggest that M phi Ao can be induced by IL-1 beta via interleukin-1 beta-converting enzyme (ICE, a cysteine protease), prostanoids, or reactive oxygen/nitrogen. However, the mechanism(s) underlying this process in septic M phi remains unknown. ⋯ However, only the nonspecific cysteine protease inhibitors (Iodo and meth) and the NO inhibitor LNMA blocked septic mouse M phi Ao. Furthermore, only PM phi from CLP mice treated with Iodo, but not LNMA or IBU, showed an improved capacity to release IL-6. We conclude that increased M phi Ao seen during sepsis appears to be mediated by both ICE-like cysteine protease activation and NO release but the level/mechanism of action of these inhibitors differs.
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When sodium nitroprusside (SNP) is used to control proximal blood pressure (Px-BP) during cross-clamping (AXC) of the thoracic aorta, it decreases spinal cord perfusion pressure (SCPP) by reducing distal aortic pressure (Ds-BP) and increasing cerebrospinal fluid pressure (CSFP). The decrease cannot be reversed by CSF drainage (CSFD) because such drainage is limited by a reduction in compliance of the spinal canal. Nitroglycerin can also be used to control Px-BP, but its effect on CSF dynamics has not previously been investigated. ⋯ CSFD cannot counteract the negative effects of SNP on SCPP; therefore, SNP contributes to postoperative paraplegia. The effects of NTG on cerebrospinal fluid dynamics are different from those of SNP. We caution surgeons against the use of NTG without CSFD during aortic cross-clamping.
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Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). ⋯ Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.
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Acute hemorrhage is associated with a variety of physiologic and metabolic alterations, including vascular hyporeactivity and endothelial cell dysfunction. The lung is a major target organ during hemorrhagic shock. The effect of acute hemorrhage on NO production in the lung is not well described. ⋯ NOe in the intact condition. NOe began to rise immediately after exsanguination began, and therefore may be a useful early marker of acute hemorrhagic shock and hypovolemia. This information may be useful in the intensive care setting.