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 purpose of this investigation was to compare the effects of initial resuscitation with HBOC-201 to that of lactated Ringer (LR) solution in the setting of uncontrolled hemorrhage and traumatic brain injury (TBI). Anesthetized immature swine underwent fluid-percussion TBI and liver laceration. During a 75-min "prehospital phase," the animals were resuscitated with HBOC-201, LR solution, or nothing (NON). ⋯ Severity of subarachnoid and intraparenchymal hemorrhages was statistically greater in LR solution-treated animals, but these differences were not likely to be clinically significant. There were no differences in glial fibrillary acidic protein and microtubule-associated protein 2. In this model of combined uncontrolled hemorrhage and TBI, initial resuscitation with HBOC-201 resulted in significant improvements in survival and systemic and cerebrovascular physiological parameters, as well as a reduction in transfusion requirements.
-
Previously, we have shown that small arterial trauma is accompanied by a decreased capability of both toll-like receptors (TLRs) 2 and 4 to respond to stimulation with their respective ligands Pam3Cys and LPS. In this study, we assessed whether surgical arterial trauma induces a decrease in the TLR response and investigated the time course of the altered responsiveness. In addition, TLR responsiveness was related to baseline patient characteristics. ⋯ Toll-like receptor 2 and 4 response declines rapidly after arterial trauma in patients undergoing vascular surgery. These results point to a significant role for TLRs in the induction of postoperative immune tolerance. Furthermore, smoking is negatively related to baseline TLR response.
-
The IL-1 receptor-associated kinase 1 (IRAK-1) and IRAK-M are key signaling molecules in cellular responses to endotoxin initiated through the Toll-like receptors (TLRs). The aim of this study was to evaluate the effect of age on the modulation of TLRs and IRAK-1 and IRAK-M in peripheral blood mononuclear cells (PBMCs) exposed in vitro to endotoxin under conditions that could induce endotoxin tolerance. Peripheral blood mononuclear cells obtained from young (4- to 6-month-old) and aged (24- to 26-month-old) Brown Norway rats were treated with high-dose LPS, with or without priming with low-dose LPS. ⋯ In contrast, PBMCs from aged rats treated in this manner continued to express measurable levels of IRAK-1 protein. Preconditioning with low-dose LPS caused an increase in both IRAK-M protein and mRNA (P = 0.05) after stimulation with high-dose LPS only in cells from young rats. These phenotypic characteristics of PBMCs from aged rats can interfere with their ability to develop tolerance to endotoxin.
-
The long pentraxin 3 (PTX3) is an important element of the innate immune system and has potential as a diagnostic tool in inflammatory conditions. We studied PTX3 in patients admitted to an intensive care unit with severe meningococcal disease and compared it with the short pentraxin C-reactive protein (CRP). Twenty-six patients with meningococcal disease were studied, 17 patients presented with meningococcal septic shock (shock group), and 9 patients presented with meningococcal meningitis or bacteremia (no-shock group). ⋯ PTX3 at admission and PTX3 peak concentration both showed a negative correlation with plasma fibrinogen concentrations. C-reactive protein concentration at admission correlated negatively with disease severity. In conclusion, PTX3 was an early indicator of shock in patients with severe meningococcal disease that followed a pattern of induction distinct from CRP.
-
We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials. ⋯ A complex porcine model of polytrauma and shock can be used for multi-institutional study with excellent reproducibility. A consistent severe injury profile was achieved, after which experimental interventions can be applied. This is the first report of a reproducible multicenter trauma and resuscitation-related animal model.