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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Recent studies have demonstrated that intralipid (ILP) conferred myocardial protection against ischemia-reperfusion (IR) injury through activation of reperfusion injury salvage kinase (RISK) pathway. As RISK signal has been shown to be impaired in hypertrophied myocardium, we investigated whether ILP-induced cardiac protection was maintained in hypertrophied rat hearts. Transverse aortic constriction was performed on male Sprague-Dawley rats to induce left ventricular hypertrophy, then sham-operated or hypertrophied rat hearts were isolated and perfused retrogradely by the Langendorff for 30 min (equilibration) followed by 40 min of ischemia and then 120 min of reperfusion. ⋯ In contrast, ischemic preconditioning increased the phosphorylation of Akt, ERK1/2 and GSK3β, improved heart pump function, and reduced myocardial necrosis in sham-operated hearts, a phenomenon partially attenuated by ventricular hypertrophy. Interestingly, GSK inhibitor SB216763 conferred cardioprotection against IR injury in sham-operated hearts, but failed to exert cardioprotection in hypertrophied myocardium. Our results indicated that ventricular hypertrophy abrogated ILP-induced cardioprotection against IR injury by alteration of RISK/GSK3β signal.
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Red blood cell (RBC) transfusions are commonplace in the intensive care unit (ICU) with at least 30% of ICU patients receiving a RBC transfusion at some point during their ICU stay. However, which patients should be transfused and what transfusion trigger(s) should be used remains unclear. ⋯ The need for blood transfusion and the benefit/risk ratio vary according to individual patient characteristics, including age and comorbidities, so large-scale RCTs in heterogeneous groups of patients may not be the most appropriate tool to investigate these issues; smaller RCTs in carefully defined patient groups may provide more useful information. Rigorous statistical analysis of large, carefully conducted observational studies will also help enhance our evidence-base in this field.
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The control of torso and junctional zone bleeding in combat casualties is particularly challenging because of its noncompressible nature. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has demonstrated promise in translational large animal and early clinical series as an effective resuscitation and hemorrhage control adjunct. However, it is unknown what proportion of combat casualties has an injury pattern and clinical course that is amenable to REBOA deployment. ⋯ The median (interquartile range) time to death in patients dying en route was 75 (42-109) min, and the median prehospital time for casualties admitted to hospital was 61 (34-89) min. One-in-five severely injured UK combat casualties have a focus of hemorrhage in the abdomen or pelvic junctional region potentially amenable to REBOA deployment. The UK military should explore REBOA as a potential en route hemorrhage control and resuscitation adjunct.
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Small molecule nonpeptidyl molecules are potentially attractive drug candidates as adjunct therapies in the treatment of sepsis-induced metabolic complications. As such, the current study investigates the use of aurintricarboxylic acid (ATA), which stimulates insulinlike growth factor 1 receptor and AKT signaling, for its ability to ameliorate the protein metabolic effects of endotoxin (lipopolysaccharide [LPS]) + interferon γ (IFN-γ) in C2C12 myotubes and sepsis in skeletal muscle. Aurintricarboxylic acid dose- and time-dependently increases mTOR (mammalian or mechanistic target of rapamycin)-dependent protein synthesis. ⋯ The ability of ATA to antagonize LPS/IFN-γ-induced changes in protein metabolism was associated with its ability to prevent the increases in interleukin 6 and nitric oxide synthase 2 and decreases in insulinlike growth factor 1. In vivo studies indicate ATA acutely increases skeletal muscle, but not cardiac, protein synthesis and attenuates the loss of lean body mass over 5 days. These data suggest ATA and other small molecule agonists of endogenous anabolic hormones may prove beneficial in treating sepsis by decreasing the inflammatory response and improving muscle protein balance.
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Military experience and recent in vitro laboratory data provide a biological rationale for whole-blood use in the treatment of exsanguinating hemorrhage and have renewed interest in the reintroduction of fresh whole blood and cold-stored whole blood to patient care in austere environments. There is scant evidence to support, in a field environment, that a whole blood-based resuscitation strategy is superior to a crystalloid/colloid approach even when augmented by a limited number of red blood cell (RBC) and plasma units. Recent retrospective evidence suggests that, in this setting, resuscitation with a full compliment of RBCs, plasma, and platelets may offer an advantage, especially under conditions where evacuation is delayed. ⋯ Combat medics will need proper protocol-based guidance and education if whole-blood collection and transfusion are to be successfully and safely performed in austere environments. In this article, we present the Norwegian Naval Special Operation Commando unit-specific remote damage control resuscitation protocol, which includes field collection and transfusion of whole blood. This protocol can serve as a template for others to use and adjust for their own military or civilian unit-specific needs and capabilities for care in austere environments.