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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We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR). ⋯ Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.
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Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. Cell necroptosis features receptor-interacting protein (RIPK) 1 activation and necroptosome formation. This leads to loss of plasma membrane integrity, the release of cell contents into the extracellular space, and subsequent increased inflammation. ⋯ Using an in vivo mouse model of intratracheal injection (i.t.) of LPS and in vitro LPS stimulation of mouse PMN, we found that LPS-TLR4 signaling in PMNs activates and phosphorylates TBK1 and IKKε, which in turn suppress LPS-induced formation of the RIPK1-RIPK3-MLKL (necrosome) complex. TBK1 dysfunction by knockdown or inhibitor significantly increases the phosphorylation of RIPK1 (∼67%), RIPK3 (∼68%), and MLKL (∼50%) and promotes RIPK1-RIPK3 and RIPK3-MLKL interactions and increases PMN necroptosis (∼83%) in response to LPS, with subsequent augmented lung inflammation. These findings suggest that the LPS-TLR4-TBK1 axis serves as a negative regulator for PMN necroptosis and might be a therapeutic target for modulating PMN death and inflammation.
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In activated immune cells, differentiation and function are determined by cell type-specific modifications of metabolic patterns. After traumatic brain injury both immune cell activation and suppression were reported. Therefore, we sought to explore immune cell energy metabolism in a long-term, resuscitated porcine model of acute subdural hematoma (ASDH)-induced acute brain injury devoid of impaired systemic hemodynamics and oxygen transport. ⋯ Principal component analysis was followed by a varimax rotation on the covariance across all measured variables and all measured time points. After ASDH induction, average PBMC metabolic activity remained unaffected, possibly because strict adherence to intensive care unit guidelines limited trauma to ASDH induction without any change in parameters of systemic hemodynamics, oxygen transport, and whole-body metabolism. Despite decreased glycolytic activity fueling the TCA cycle, the principal component analysis indicated a cell type-specific activation pattern with biosynthetic and proliferative characteristics.
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Non-compressible torso hemorrhage (NCTH) is the leading cause of potentially preventable death on the battlefield. Resuscitative endovascular balloon occlusion of the aorta (REBOA) aims to restore central blood pressure and control NCTH below the balloon, but risks ischemia-reperfusion injury to distal organs when prolonged. We tested a bilobed partial REBOA catheter (pREBOA), which permits some of the blood to flow past the balloon. ⋯ In this porcine model of hemorrhagic shock, animals undergoing partial REBOA for 120 min survived longer than those undergoing full occlusion.
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The effect of analgesia on physiological systems has received little attention in trauma research. Our aim was to examine the effect of two different analgesics, buprenorphine and carprofen, on adenosine, lidocaine, and magnesium (ALM) resuscitation in a rat model of laparotomy and non-compressible hemorrhage. Male Sprague-Dawley rats were randomly assigned to Saline Carprieve, ALM Carprieve, Saline Buprenorphine, or ALM Buprenorphine (all n = 10). ⋯ No analgesic-related differences were found in total white cells, lymphocytes, platelet count, hyperthermia, weight loss, or pica. We conclude that reduced survival and MAP recovery appears to a buprenorphine effect on cardiovascular function. Until the underlying mechanisms can be elucidated, buprenorphine should be used with caution in small and possibly large models of trauma and shock.