Thrombin Generation Following Severe Trauma: Mechanisms, Modulators, and Implications for Hemostasis and Thrombosis
Thrombin is the central coagulation enzyme that catalyzes the conversion of fibrinogen to form insoluble fibrin blood clots. In vivo, thrombin production results from the concerted effort of plasma enzymatic reactions with essential contributions from circulating and vessel wall cells. The relative amount of thrombin produced directly dictates the structure and stability of fibrin clots; therefore, sufficient thrombin generation is essential for normal hemostasis to occur. Examination of thrombin generation phenotypes among severely injury trauma patients reveals important relationships between the potential for generating...
Source: Shock - October 21, 2021 Category: Emergency Medicine Tags: Review Articles Source Type: research
Cannabinoid Receptor 1 and 2 Signaling Pathways Involved in Sepsis
Sepsis is defined as a life-threatening organ dysfunction, caused by a dysregulated host response to an infection and can progress to septic shock, which represents a major challenge in critical care with a high mortality rate. Currently, there is no definitive treatment available for the dysregulated immune response in sepsis. Therefore, a better understanding of the pathophysiological mechanisms may be useful for elucidating the molecular basis of sepsis and may contribute to the development of new therapeutic strategies. The endocannabinoid system is an emerging research topic for the modulation of the host immune respo...
Source: Shock - October 21, 2021 Category: Emergency Medicine Tags: Review Articles Source Type: research
Cytokine Drizzle—The Rationale for Abandoning “Cytokine Storm”
Conclusion:
The misleading term “cytokine storm” implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term “cytokine storm”. “Cytokine storm” should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors. (Source: Shock)
Source: Shock - October 21, 2021 Category: Emergency Medicine Tags: Review Articles Source Type: research
Myeloid-Derived Suppressor Cells (MDSCs) and the Immunoinflammatory Response to Injury (Mini Review)
Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells hallmarked by their potent immunosuppressive function in a vast array of pathologic conditions. MDSCs have recently been shown to exhibit marked expansion in acute inflammatory states including traumatic injury, burn, and sepsis. Although MDSCs have been well characterized in cancer, there are significant gaps in our knowledge of their functionality in trauma and sepsis, and their clinical significance remains unclear. It is suggested that MDSCs serve an important role in quelling profound inflammatory responses in the acute se...
Source: Shock - October 21, 2021 Category: Emergency Medicine Tags: Mini-Review Article Source Type: research
What's New in Shock, November 2021?
No abstract available (Source: Shock)
Source: Shock - October 21, 2021 Category: Emergency Medicine Tags: Commentary Source Type: research
End-tidal Carbon Dioxide as an Indicator of Partial REBOA and Distal Organ Metabolism in Normovolemia and Hemorrhagic Shock in Anesthetized Pigs
Conclusion:
ETCO2 was correlated to distal aortic blood flow and VO2 during incremental degrees of aortic occlusion thereby potentially reflecting the degree of aortic occlusion and the ischemic consequences of partial REBOA. Further studies of ETCO2, and potential confounders, in partial REBOA are needed before clinical use. (Source: Shock)
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Levosimendan Ameliorates Post-resuscitation Acute Intestinal Microcirculation Dysfunction Partly Independent of its Effects on Systemic Circulation: A Pilot Study on Cardiac Arrest in a Rat Model
This study preliminarily investigated the link between dynamic changes in intestine and systemic hemodynamics post-resuscitation after levosimendan administration.
Methods:
Twenty-five rats were randomized into three groups: sham control group (n = 5), levosimendan group (n = 10), and vehicle group (n = 10). Intestinal microcirculation was observed using a sidestream dark-field imaging device at baseline and each hour of the return of spontaneous circulation (≤6 h). Systemic hemodynamics, serum indicators of cardiac injury, and tissue perfusion/metabolism were measured by echo-cardiography, a biologi...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
MUC1 Mitigates Renal Injury and Inflammation in Endotoxin-Induced Acute Kidney Injury by Inhibiting the TLR4-MD2 Axis and Reducing Pro-inflammatory Macrophages Infiltration
Sepsis is the leading cause of acute kidney injury (AKI) in critical care patients. A cornerstone of sepsis-associated AKI is dysregulated inflammation driven by excessive activation of Toll-like receptor 4 (TLR4) pathway. MUC1, a membrane-bound mucin expressed in both epithelial tubular cells and renal macrophages, has been shown to be involved in the regulation of TLRs. Therefore, we hypothesized that MUC1 could mitigate the renal inflammatory response to TLR4 activation. To test this hypothesis, we used a murine model of endotoxin-induced AKI by intraperitoneal injection of LPS. We showed that Muc1−/− mice have a mo...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Membrane Permeant Inhibitor of Myosin Light Chain Kinase Worsens Survival in Murine Polymicrobial Sepsis
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Genetic deletion of myosin light chain kinase (MLCK) reverses intestinal hyperpermeability and improves survival in a murine model of intra-abdominal sepsis. In an attempt to determine whether these findings could be translated using a more clinically relevant strategy, this study aimed to determine if pharmacologic inhibition of MLCK using the membrane permeant inhibitor of MLCK (PIK) improved gut barrier function and survival following sepsis. C57B...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Estrogen Enhances the Microvascular Reactivity Through RhoA-ROCK Pathway in Female Mice During Hemorrhagic Shock
This study observed whether E2 can restore vascular hypo-reactivity induced by hemorrhagic shock, and whether E2 effects are associated with RhoA-Rho kinase (ROCK)-myosin light chain kinase phosphatase (MLCP) pathway. The hemorrhagic shock model (40 ± 2 mm Hg for 1 h, resuscitation for 4 h) was established in ovary intact sham operation (OVI), ovariectomized (OVX), and OVX plus E2 supplement female mice. Intestinal microvascular loop was used to assess blood flow in vivo, mRNA expression and vascular reactivity in vitro. Hemorrhagic shock significantly reduced norepinephrine microvascular reactivity. Decreased m...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Hypobaria Exposure Worsens Cardiac Function and Endothelial Injury in AN Animal Model of Polytrauma: Implications for Aeromedical Evacuation
Background:
Aeromedical evacuation can expose traumatically injured patients to low pressure (hypobaria) and hypoxia. Here, we sought to assess the impact of hypobaria on inflammation, organ injury, and mortality in a mouse model of polytrauma.
Methods:
Eight to 12-week-old male C57BL/6J mice were subjected to sham or polytrauma consisting of bowel ischemia by superior mesenteric artery occlusion, hindlimb muscle crush, and tibia fracture. Two hours after injury, animals were randomized to undergo either 6 h of hypobaria or sea-level, room air conditions. At 8 or 24 h after injury, transthoracic echocardiogr...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Inhalation of 2% Hydrogen Improves Survival Rate and Attenuates Shedding of Vascular Endothelial Glycocalyx in Rats with Heat Stroke
Heat stroke is characterized by excessive oxidative stress and inflammatory responses, both of which are implicated in vascular endothelial glycocalyx shedding and heat-stroke mortality. Although molecular hydrogen has antioxidation and anti-inflammatory potency, its effect on the vascular endothelial glycocalyx in heat stroke has not been examined. Therefore, the aim of this study was to investigate the influence of hydrogen inhalation on the survival and thickness of the vascular endothelial glycocalyx of rats subjected to heat stroke. Altogether, 98 Wistar rats were assigned to the experiments. A heat-controlled chamber...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
The Long-term Effect of Dobutamine on Intrinsic Myocardial Function and Myocardial Injury in Septic Rats with Myocardial Dysfunction
This study investigated the long-term effect of DOB on septic myocardial dysfunction and injury. Rats were exposed to cecal ligation and puncture (CLP), the intrinsic myocardial function, other organ functions, hemodynamics, inflammatory response, serum myocardial injury biomarkers, myocardial apoptosis, and vascular permeability were determined. At 6 h after CLP, the left ventricular ±dP/dt were significantly depressed, cardiac tumor necrosis factor-α and vascular cell adhesion molecule-1 expression were increased, but not serum cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-typ...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Involvement of NF-κB1 and the Non-canonical NF-κB Signaling Pathway in the Pathogenesis of Acute Kidney Injury in Shiga-toxin-2-induced Hemolytic-uremic Syndrome in Mice
The hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy which can occur as a severe systemic complication after an infection with Shiga-toxin-(Stx)-producing Escherichia coli (STEC). Elevated levels of proinflammatory cytokines associated with the classical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) signaling pathway were detected in the urine of HUS patients. Thus, we hypothesize that the immune response of the infected organism triggered by Stx can affect the kidneys and contributes to acute kidney injury. Hitherto, the role of the classical and non-canonical NF-κB signaling path...
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
A Prediction Model for Assessing Prognosis in Critically Ill Patients with Sepsis-associated Acute Kidney Injury
Conclusions:
Our SAKI model has predictive value for in-hospital mortality of SA-AKI in critically ill patients and outperforms generic scores. (Source: Shock)
Source: Shock - September 23, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research
