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
-
The aim of the present study was to investigate the effects of lipopolysaccharide (LPS) on the contractile response induced by electrical field stimulation (EFS) in rat mesenteric segments, as well as the mechanisms involved. Effects of LPS incubation for 2 or 5 h were studied in mesenteric segments from male Wistar rats. Vasomotor responses to EFS, nitric oxide (NO) donor DEA-NO, and noradrenaline (NA) were studied. ⋯ Short-term exposure of rat mesenteric arteries to LPS produced a time-dependent enhanced contractile response to EFS. The early phase (2 h) was associated to a reduction in NO from neuronal NO synthase and an enhanced response to NA. After 5 h of LPS exposure, this enhancement was reduced, because of restoration of the adrenergic component and maintenance of the nitrergic reduction.
-
The hemoglobin vesicle (Hb-vesicle) is a cellular-type artificial oxygen carrier showing a resuscitative effect comparable to that of blood transfusion in several animal models. However, the efficacy of Hb-vesicles for resuscitation when the hemorrhage cannot be controlled remains unclear. Therefore, we used Hb-vesicles in a rat hemorrhagic shock model caused by continuous bleeding. ⋯ Meanwhile, the hematocrit levels of the HbV, Alb, and HES groups showed sharp decreases (HbV: 6.8% ± 1.7%, Alb: 6.8% ± 0.8%, HES: 5.5% ± 0.7% at 100% total circulated blood volume; final hematocrit of the HbV group: 1.5% ± 0.5%). These results suggest that shocked animals can survive longer when the Hb-vesicle supply is maintained and that HbV showed a similar effect to wRBC in maintaining the circulating volume and oxygen metabolism. Continuous infusion of Hb-vesicles may extend the survival of trauma victims with uncontrolled hemorrhage until they have reached a trauma center.
-
Human C1 inhibitor (C1INH) prevents endotoxin shock via a direct interaction with Gram-negative bacterial lipopolysaccharide (LPS) and improves survival in animal models of sepsis. In this report, we further characterize the interaction of C1INH with LPS and whole live bacteria. We investigate C1INH interactions with LPS from five different strains of Gram-negative enteric bacteria known to participate in the pathogenesis of human sepsis. ⋯ The binding of both native and reactive center-cleaved, inactive C1INH results in inhibition of LPS-induced proinflammatory cytokine production. Furthermore, we demonstrate the ability of C1INH to bind at the surface of only a restricted number of whole live Gram-negative bacteria as well as mutant bacteria expressing a truncated LPS lacking the O-antigen. These data reveal the interaction of C1INH with a wide range of enteric bacterial LPS and strongly suggest that the interaction between C1INH and the surface of Gram-negative microorganisms is determined by the length of the polysaccharide chain of the endotoxin molecule.
-
Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counterinflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. ⋯ In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients.
-
Randomized Controlled Trial
Continuous enteral and parenteral feeding each reduces heart rate variability but differentially influences monocyte gene expression in humans.
Enteral (EN) or parenteral (PN) nutrition is used to support critically ill patients until oral feeding resumes. Enteral nutrition is assumed preferable to PN, but the differential influence on immune function is not well defined. Autonomic nervous activity is known to influence innate immune responses, and we hypothesized that EN and PN could influence both autonomic signaling and gene activation in peripheral blood monocytes (PBMs). ⋯ However, PN feeding had a much greater influence on PBM gene expression compared with baseline than EN, including genes important to innate immunity. Continuous EN and PN are both associated with decreasing vagal tone over time, yet contribute differently to PBM gene expression, in humans. These preliminary findings support assumptions that PN imposes a systemic inflammatory risk but also imply that continuous feeding, independent of route, may impart additional risk through different mechanisms.