Shock

INTRODUCTION: Rats subjected to polytrauma and hemorrhage develop a coagulopathy that is similar to acute coagulopathy of trauma in humans, and is associated with a rise in prothrombin time and a fall in clot strength. Because platelet aggregation accounts for a major proportion of clot strength, we set out to characterize the effects of polytrauma on platelet function. METHODS: Sprague-Dawley rats were anesthetized with isoflurane. Polytrauma included laparotomy and damage to 10 cm of the small intestines, right and medial liver lobes, right leg skeletal muscle, femur fracture, and hemorrhage (40% of blood volume)...

Clinical data has supported the early use of plasma in high ratios of plasma to red cells to patients in hemorrhagic shock. The benefit from plasma seems to extend beyond its hemostatic effects to include protection to the post-shock dysfunctional endothelium. Resuscitation of the endothelium by plasma and one of its major constituents, fibrinogen, involves cell surface stabilization of syndecan-1, a transmembrane proteoglycan and the protein backbone of the endothelial glycocalyx. The pathogenic role of miRNA-19b to the endothelium is explored along with the PAK-1 mediated intracellular pathway that may link syndecan-1 to cytoskeletal protection...

Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion primarily due to cardiac dysfunction. This condition is the most common cause of death in patients affected by acute myocardial infarction (AMI). Despite early revascularization, prompt optimal medical therapy, and up-to-date mechanical circulatory supports, mortality of patients with CS remains high.The objective of this review is to summarize epidemiology, pathophysiology, and treatment options of CS in light of the new European Society of cardiology (ESC) recommendations...

BACKGROUND: Pulmonary infections remain the most common cause of Acute Respiratory Distress Syndrome (ARDS), a pulmonary inflammatory disease with high mortality, for which no targeted therapy currently exists. We have previously demonstrated an ameliorated syndrome with early, broad spectrum Histone Deacetylase (HDAC) inhibition in a murine model of gram-negative pneumonia-induced Acute Lung Injury (ALI), the underlying pulmonary pathologic phenotype leading to ARDS. With the current project we aim to determine if selective inhibition of a specific HDAC leads to a similar pro-survival phenotype, potentially pointing to a future therapeutic target...

BACKGROUND: Fever is common in mechanically ventilated patients and may be uniquely detrimental in those with lung injury because of its injurious effects on pulmonary vascular permeability and alveolar epithelium. We evaluated the association of fever and antipyretic medication with mortality in mechanically ventilated emergency department (ED) patients. METHODS: This is a retrospective cohort study of 1264 patients requiring mechanical ventilation initiated in the ED with subsequent admission to an intensive care unit...

BACKGROUND: Thirty-day mortality in ST-elevation myocardial infarction (STEMI) patients is primarily driven by cardiogenic shock (CS). High neutrophil counts and high neutrophil/lymphocyte ratios (NLR) have previously been associated with mortality in STEMI patients, however, there is only sparse knowledge regarding their association with CS. PURPOSE: We sought to assess the associations between neutrophil count and NLR with the development of CS as well as 30-day mortality in STEMI patients...

BACKGROUND: Hemorrhage is the leading cause of preventable, traumatic death. Currently, pre-hospital resuscitation fluids provide preload but not oxygen carrying capacity-a critical blood function that mitigates microvascular ischemia and tissue hypoxia during hemorrhagic shock. Solutions containing polymerized hemoglobin have been associated with vasoactive and hypertensive events. A novel hemoglobin-based oxygen carrier, modified with PEGylation and CO moieties (PEG-COHb) may overcome these limitations...

OBJECTIVES: To evaluate the dose effects of Recombinant human Club cell 10-kDa protein (rhCC10) on lung function in a well-characterized ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation injury (SII). Specifically, the potential of rhCC10 protein to control the inflammatory response and protect pulmonary tissue and function following SII. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal ICU...

BACKGROUND: Monophosphoryl lipid A (MPLA) is a TLR4 agonist that has potent immunomodulatory properties and modulates innate immune function to improve host resistance to infection with common nosocomial pathogens in mice. The goal of this study was to assess the safety and efficacy of MPLA in a sheep model of burn injury and Pseudomonas aeruginosa pneumonia. The sheep provides a favorable model for preclinical testing as their response to TLR4 agonists closely mimics that of humans. METHODS: Twelve chronically instrumented adult female Merino sheep received 20% total body surface area, third-degree cutaneous burn under anesthesia and analgesia...

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BACKGROUND: Uncontrolled bleeding is the main cause of the potential preventable death in trauma patients. Accordingly, we reviewed all the existing scores for massive transfusion posttraumatic hemorrhage and summarized their characteristics, thus making it easier for the reader to have a global view of these scores - how they were created, their accuracy and to which population they apply. METHODS: A narrative review with a systematic search method to retrieve the journal articles on the predictive scores or models for massive transfusion was carried out...

AIM: Comparing the effects of different vasopressors in septic shock patients is hampered by high heterogeneity and the fact that current guidelines dictate the use of norepinephrine. Herein, we studied the effects of three vasopressor agents, norepinephrine, phenylephrine and vasopressin, on the macro- and microcirculation during experimental human endotoxemia, a standardized, controlled model of systemic inflammation in humans in vivo. METHODS: We performed a randomized controlled study in which 40 healthy male volunteers were assigned to a five-hour infusion of either 0...

BACKGROUND: Patients with septic shock in whom Norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of Vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP...

BACKGROUND: Major trauma leads to complex immune reactions, known to result in a transient immunodeficiency. The long-term consequences of severe trauma on immune function and regulation as well as its clinical impact remain unclear. METHODS: Six months (ranging from -12 to +5 days) after a major trauma event, 12 former trauma patients (ISS ≥ 16) and 12 healthy volunteers were enrolled. The current clinical status and infection history since discharge were assessed by a standardized questionnaire...

The intestinal mucosa plays a critical role in the organism, acting as an interface between the lamina propria and the harmful antigens in the lumen. Sepsis is associated with primary injury to the intestinal mucosa, which in turn induces bacterial translocation and hyperpermeability. Cholecystokinin (CCK) is a peptide synthesized by several cell types, whose immunomodulatory activity has been reported in experimental models of inflammation. We hypothesized that the CCK treatment could modulate the inflammatory response and protect the integrity of the intestinal barrier in endotoxemic rats...

INTRODUCTION: The knowledge of the prognostic value of prehospital lactate (PLA) is limited. Our objective was to evaluate the predictive capacity of PLA to predict early mortality (within 48 hours) from the index event in acute cardiovascular disease (ACVD). METHODS: Prospective, longitudinal, multicenter, observational study in patients attended by advanced life support units, transferred to the emergency department of their reference hospital and diagnosed with ACVD...

Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and LPS. The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS.Female CD1 mice had radiotelemetry probes implanted to measure haemodynamic function non-invasively and were time-mated...

OBJECTIVE: To investigate the changes of bile acids in the liver during hemorrhagic shock (HS) and their potential to attenuate liver injury via activation of SIRT1 (sirtuin 1)-FXR (farnesoid X receptor) signaling. METHODS: A Sprague-Dawley (SD) rat HS model was established, while HepG2 cells were hypoxically cultured to simulate HS in vitro. Liver bile acids (BA) were profiled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). FXR expression was detected by western blot and immunohistochemistry...

BACKGROUND: Activation of the complement system and complement deposition on red blood cells (RBCs) contribute to organ damage in trauma. We conducted a prospective study in subjects with traumatic injuries to determine the pattern of complement deposition on RBC and whether they are associated with clinical outcomes. METHOD: A total of 124 trauma patients and 42 healthy controls were enrolled in this prospective study. RBC and sera were collected at 0, 6, 24 and 72 hours from trauma patients and healthy controls during a single draw...

BACKGROUND: A declining selenium (Se) status constitutes a characteristic of critical illness and may affect disease course and survival. The dynamics of trauma-induced changes in biomarkers of Se status are poorly characterized, and an association with multiple organ failure (MOF) and mortality can be hypothesized. It was the aim of this study to investigate Se and selenoprotein P (SELENOP) concentrations in major trauma patients during the early posttraumatic period. PATIENTS AND METHODS: Twenty-four patients after major trauma (ISS ≥16) were included at our level one trauma center...