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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Along with redistributive shock, myocardial dysfunction is now recognized as highly prevalent in early severe sepsis. Indeed, aside from their distinct loading potency, resuscitation fluids have been poorly investigated as to their specific molecular impact on myocardial dysfunction. The objective of this study was to evaluate the load-independent biological impact of different resuscitation fluids on endotoxin-induced myocardial dysfunction. ⋯ Hypertonic saline solution was also cardioprotective by early prevention of myocardial dysfunction and by reducing cardiac apoptosis. Fluid infusions have distinct load-independent structural/biological impacts on endotoxin-induced myocardial dysfunction. Albumin and hypertonic saline solution are the most pleiotropic fluids in protecting the heart after a "sepsis" hit.
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This study was designed to follow the time course of inflammatory activation in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. We hypothesized that oral phosphatidylcholine (PC) pretreatment regimens may influence leukocyte-mediated microcirculatory reactions in this condition. In series I, Wistar rats were monitored 1 day after colitis induction (n = 24), and in series II (n = 24) on day 6 following a TNBS enema. ⋯ The PC pretreatment protocols led to significant decreases in the serosal hyperemic reaction, the cytokine levels, and the inflammatory enzyme activities. The objective signs of tissue damage were reduced in both series, and the number of mucus-producing goblet cells in the resolving phase of colitis was increased. Dietary PC efficiently decreases the cytokine-mediated progression of inflammatory events and preserves the microvascular structure in the large intestine.
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Aberrant activation of neutrophils during sepsis results in the widespread release of proinflammatory mediators, leading to multiorgan system failure and death. However, aberrant activation of neutrophils during sepsis results in the widespread release of harmful inflammatory mediators causing host tissue injuries that can lead to multiorgan system failure and death. ⋯ Second, β1 integrin (CD29) was highly upregulated on the neutrophils isolated from both septic patients and animals. Finally, conditional genetic ablation of β1 integrin from granulocytes also improved survival and bacterial clearance in septic animals Thus, our results indicate that expression of β1 integrin is important for modulating neutrophil trafficking during sepsis and that therapeutics designed against β1 integrins may be beneficial.
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Large surface area burn injuries lead to activation of the innate immune system, which can be blocked by parasympathetic inputs mediated by the vagus nerve. We hypothesized that vagal nerve stimulation (VNS) would alter the inflammatory response of peritoneal macrophages after severe burn injury. Male BALB/c mice underwent right cervical VNS before 30% total body surface area steam burn and were compared with animals subjected to burn alone. ⋯ We identified a protective role for VNS in blocking peritoneal macrophage activation. Analysis of the phosphorylation state of nuclear factor κB pathway mediator, p65 Rel A, revealed a VNS-mediated reduction in p65 phosphorylation levels after exposure to LPS compared with burn alone. In combination, these studies suggest VNS mediates the inflammatory response in peritoneal macrophages by affecting the set point of LPS responsiveness.
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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.