Background: Red blood cell (RBC) aggregation can be initiated by calcium and tissue factor, which may independently contribute to microvascular and macrovascular thrombosis after injury and transfusion. Previous studies have demonstrated that increased blood storage duration may contribute to thrombotic events. The aims of this study were to first determine the effect of blood product components, age, and hematocrit (HCT) on the aggregability of RBCs, followed by measurement of RBC aggregability in two specific injury models including traumatic brain injury (TBI) and hemorrhagic shock.
View Article and Find Full Text PDFIntroduction: Large-volume packed red blood cell (pRBC) transfusion is associated with lung injury and worsened outcomes. Amitriptyline reduces lung injury and inflammation in a murine sepsis model. We hypothesized that red cell microparticles (MP) activate endothelial cells, leading to lung injury and that treatment with amitriptyline would blunt the inflammatory response MPs through inhibition of acid sphingomyelinase (ASM).
View Article and Find Full Text PDFIntroduction: The red blood cell (RBC) storage lesion has been well described in mouse and human blood but not in swine. Understanding the porcine RBC storage lesion is necessary prior to evaluating transfusion of stored packed red blood cells (pRBCs) in polytrauma models. We hypothesized that porcine pRBCs would undergo a similar storage lesion severity after 42 d.
View Article and Find Full Text PDFBackground: The use of whole blood compared with a balanced ratio of components in trauma resuscitation remains an area of ongoing investigation. One factor that may affect outcomes is the age of the blood product transfused. We used a murine model of blood banking and hemorrhagic shock resuscitation to compare the effect of storage duration in whole blood and packed red blood cells on the recipient inflammatory response.
View Article and Find Full Text PDFIntroduction: Splenectomy (SPLN) is associated with elevated risk of venous thromboembolic (VTE) disease. Enoxaparin (ENX) is a low-molecular-weight heparin agent used in VTE chemoprophylaxis. Early aspirin administration ameliorates postSPLN platelet hyperaggregability in male mice.
View Article and Find Full Text PDFIntroduction: Hypoxia is a significant cause of secondary insult in the critically ill trauma or surgical patient. The cause of increased mortality following a brief period of hypoxia is not well understood. The aim of this study is to determine the effect of acute, isolated deviations in oxygen concentration on proinflammatory cytokine release and markers of endothelial stress in a murine model.
View Article and Find Full Text PDFIntroduction: Many patients suffering from isolated severe traumatic brain injury (sTBI) receive blood transfusion on hospital arrival due to hypotension. We hypothesized that increasing blood transfusions in isolated sTBI patients would be associated with an increase in mortality.
Methods: We performed a trauma quality improvement program (TQIP) (2017-2019) and single-center (2013-2021) database review filtering for patients with isolated sTBI (Abbreviated Injury Scale head ≥3 and all other areas ≤2).
Background: Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is used by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation after TBI that could contribute to more severe TBI-related secondary injury.
View Article and Find Full Text PDFBackground: Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane.
View Article and Find Full Text PDFIntroduction: Whole blood resuscitation for hemorrhagic shock in trauma represents an opportunity to correct coagulopathy in trauma while also supplying red blood cells. The production of microvesicles in stored whole blood and their effect on its hemostatic parameters have not been described in previous literature. We hypothesized that microvesicles in aged stored whole blood are procoagulant and increase thrombin production via phosphatidylserine.
View Article and Find Full Text PDFIntroduction: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA.
View Article and Find Full Text PDFIntroduction: The use of packed red blood cells (pRBCs) for resuscitation is limited by the red blood cell storage lesion, a series of biochemical and physiological changes that occur during the storage and aging of blood. Microvesicles (MVs) shed from pRBCs during this process are one component of the red blood cell storage lesion and lead to acute lung injury and pulmonary vascular microthrombi. We hypothesized that MVs from stored pRBCs lead to the release of P-selectin and von Willebrand factor (vWF) from endothelial cells and that this mechanism is mediated via activation of protein kinase C (PKC) or protein kinase A (PKA).
View Article and Find Full Text PDFIntroduction: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation.
View Article and Find Full Text PDFIntroduction: Various murine models have been utilized to study TBI, including closed head injury (CHI) and controlled cortical impact (CCI), without direct comparison. The aim of our study was to evaluate these models to determine differences in neurological and behavioral outcomes postinjury.
Methods: Male C57B/6 mice (9-10 wk) were separated into six groups including: untouched, sham craniotomy (4 mm), CCI 0.
Introduction: Syndecan-1 is a heparan sulfate proteoglycan found in the glycocalyx of vascular endothelial cells. Serum levels of syndecan-1 have repeatedly been demonstrated to increase following traumatic injury and shock, but it is unclear whether syndecan-1 plays an active role in the inflammatory response or is simply a biomarker of a state of hypoperfusion. The aim of this study was to identify the role of syndecan-1 role in the inflammatory process in the absence of trauma.
View Article and Find Full Text PDFIntroduction: While previous studies have analyzed military surgeon experience within military-civilian partnerships (MCPs), there has never been an assessment of how well military providers are integrated within an MCP. The Center for Sustainment of Trauma and Readiness Skills, Cincinnati supports the Critical Care Air Transport Advanced Course and maintains the clinical skills of its staff by embedding them within the University of Cincinnati Medical Center. We hypothesized that military trauma surgeons are well integrated within University of Cincinnati Medical Center and that they are exposed to a similar range of complex surgical pathophysiology as their civilian partners.
View Article and Find Full Text PDFIntroduction: Negative pressure wound therapy (NPWT) is utilized early after soft tissue injury to promote tissue granulation and wound contraction. Early post-injury transfers via aeromedical evacuation (AE) to definitive care centers may actually induce wound bacterial proliferation. However, the effectiveness of NPWT or instillation NPWT in limiting bacterial proliferation during post-injury AE has not been studied.
View Article and Find Full Text PDFIntroduction: Seven key inflammatory biomarkers were recently found to be associated with the risk of mortality in a multicenter study of massively transfused patients. The aim of this prospective single-center study was to determine which of these early inflammatory markers could predict 30-d mortality among all critically injured trauma patients.
Methods: Serum samples were collected at 6, 24, and 72 h from 238 consecutive patients admitted to the intensive care unit following traumatic injury.
Background: Resuscitation with plasma components has been shown to improve endotheliopathy induced by hemorrhagic shock, but the optimal resuscitation strategy to preserve the endothelial glycocalyx has yet to be defined. The aim of this study was to determine if resuscitation with lactated Ringer's (LR), whole blood (WB), packed red blood cells (RBCs), platelet-rich plasma (PRP), platelet poor plasma, balanced RBC:PRP (1:1), or day 14 (d14) RBC would best minimize endothelial damage following shock.
Methods: Male C57BL/6 mice were hemorrhaged to a goal mean arterial pressure of 25 mm Hg for 1 hour.
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View Article and Find Full Text PDFIntroduction: The optimal management strategies for patients with polytraumatic injuries that include traumatic brain injury (TBI) are not well defined. Specific interventions including tranexamic acid (TXA), propranolol, and hypertonic saline (HTS) have each demonstrated benefits in patient mortality after TBI, but have not been applied to TBI patients with concomitant hemorrhage. The goals of our study were to determine the inflammatory effects of resuscitation strategy using HTS or shed whole blood (WB) and evaluate the cerebral and systemic inflammatory effects of adjunct treatment with TXA and propranolol after combined TBI + hemorrhagic shock.
View Article and Find Full Text PDFBackground: Platelet activation and aggregation are critical to the initiation of hemostasis after trauma with hemorrhage. Platelet dysfunction is a well-recognized phenomenon contributing to trauma-induced coagulopathy. The goal of this study was to evaluate the timing and severity of platelet dysfunction in massively transfused, traumatically injured patients during the first 72 hours after injury and its association with 30-day survival.
View Article and Find Full Text PDFBackground: Current management of hemorrhagic shock relies on control of surgical bleeding along with resuscitation with packed red blood cells and plasma in a 1-to-1 ratio. Transfusion, however, is not without consequence as red blood cells develop a series of biochemical and physical changes during storage termed "the red blood cell storage lesion." Previous data has suggested that ethanol may stabilize the red blood cell membrane, resulting in improved deformability.
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