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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Introduction: Severely injured patients develop a dysregulated inflammatory state characterized by vascular endothelial permeability, which contributes to multiple organ failure. To date, however, the mediators of and mechanisms for this permeability are not well established. Endothelial permeability in other inflammatory states such as sepsis is driven primarily by overactivation of the RhoA GTPase. ⋯ This study presents the largest study to date measuring endothelial permeability in vitro using plasma collected from patients after traumatic injury. Here, we demonstrate that plasma from patients who develop shock after severe traumatic injury induces endothelial permeability and increased RhoA activation in vitro. Our ECIS model of trauma-induced permeability using ex vivo plasma has potential as a high throughput screening tool to phenotype endothelial dysfunction, study mediators of trauma-induced permeability, and screen potential interventions.
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Aims: A rapid heart rate (HR) that occurs after cardiopulmonary resuscitation (CPR) is a short-term compensatory mechanism preserving cardiac output. However, if of long duration, it is unfavorable for myocardial function postresuscitation because of disrupted balance between myocardial oxygen supply and demand. This raises the assumption that such a sustained fast HR should be regulated. ⋯ Serum cardiac troponin I and epinephrine concentration were significantly higher in the ivabradine group (all P < ?0.01). Survival duration was significantly shortened in the ivabradine group as compared with the saline group (388 vs. 526 min, P < ?0.01). Conclusions: Ivabradine-induced HRR increases the severity of postresuscitation myocardial dysfunction and shortens survival duration in a rat model of CPR.
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Introduction: 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. ⋯ Conclusions: Whole blood resuscitation can reduce the acute postinjury neuroinflammatory response after combined TBI/shock compared with HTS. The addition of either propranolol or TXA may modulate the postinjury systemic and cerebral inflammatory response with more improvements noted after propranolol administration. Multimodal treatment with resuscitation and pharmacologic therapy after TBI and hemorrhagic shock may mitigate the inflammatory response to these injuries to improve recovery.
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Background: Dexmedetomidine (DEX) attenuates intestinal I/R injury, but its mechanism of action remains to be further elucidated. Protein disulfide isomerase A3 (PDIA3) has been reported as a therapeutic protein for the prevention and treatment of intestinal I/R injury. This study was to investigate whether PDIA3 is involved in intestinal protection of DEX and explore the underlying mechanisms. ⋯ PDIA3 cKO in the intestinal epithelium have reversed the protective effects of DEX. Moreover, yohimbine also reversed the intestinal protection of DEX and downregulated the messenger RNA and protein levels of PDIA3. Conclusion: DEX prevents PDIA3 decrease by activating α2-AR to inhibit intestinal I/R-induced inflammation, ER stress-dependent apoptosis, and oxidative stress in mice.
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Background: Blood type O is the most common blood type and has lower von Willebrand factor (vWF) levels (25%-35% lower than non-O blood types). von Willebrand factor is important for initiating platelet attachment and binding factor VIII. We hypothesized that patients with type O blood are at an increased risk of trauma-induced coagulopathy and bleeding post injury. Study Design: Adult trauma activations with known blood type at a level I trauma center with field systolic blood pressure < 90 mm Hg were studied retrospectively. ⋯ Other outcomes were not significantly affected. Conclusion: Type O patients with hypotension had increased HF and MT post injury, and these were associated with lower vWF activity. These findings have implications for the monitoring of HF in patients receiving type O whole-blood transfusions post injury.