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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The pathophysiology of traumatic hemorrhage is a phenomenon of vascular disruption and the symptom of bleeding represents one or more vascular injuries. In the Circulatory Trauma paradigm traumatic hemorrhage is viewed as injury to the circulatory system and suggests the underlying basis for endovascular hemorrhage control techniques. The question "Where is the patient bleeding?" is replaced by "Which blood vessels are disrupted?" and stopping bleeding becomes a matter of selective vessel access and vascular flow control. ⋯ This narrative review presents a brief overview of the current role of endovascular therapy in the management of circulatory trauma. The authors draw on their personal experience combined with the last decade of published experiences with the use of endovascular techniques in trauma and present general recommendations for their evolving use. The focus of the review is on the use of endovascular techniques as specific vascular treatments using the circulatory trauma paradigm.
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Acute lung injury (ALI) is caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis and trauma. Alveolar macrophages are the main and critical leukocytes in the airspace, and through the synthesis and release of various inflammatory mediators critically influence the development of ALI following infection and non-infectious stimuli. ⋯ In this study, we demonstrate that memantine, a N-methyl-D-aspartic acid receptor (NMDAR) antagonist, through suppressing Ca2+ influx and subsequent ASC oligomerization inhibits macrophage Nlrp3 inflammasome activation and pyroptosis, therefore, alleviates ALI in septic mice. This finding explores a novel application of memantine, an FDA already approved medication, in the treatment of ALI, which is currently lacking effective therapy.
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Meta Analysis
Therapeutically Targeting Microvascular Leakage In Experimental Hemorrhagic Shock: A Systematic Review and Meta-Analysis.
Microvascular leakage is proposed as main contributor to disturbed microcirculatory perfusion following hemorrhagic shock and fluid resuscitation, leading to organ dysfunction and unfavorable outcome. Currently, no drugs are available to reduce or prevent microvascular leakage in clinical practice. We therefore aimed to provide an overview of therapeutic agents targeting microvascular leakage following experimental hemorrhagic shock and fluid resuscitation. ⋯ CRD42018095432.
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Sepsis' pathogenesis involves multiple mechanisms that lead to a dysregulation of the host's response. Significant efforts have been made in search of interventions that can reverse this situation and increase patient survival. Poly (ADP-polymerase) (PARP) is a constitutive nuclear and mitochondrial enzyme, which functions as a co-activator and co-repressor of gene transcription, thus regulating the production of inflammatory mediators. ⋯ The benefit of olaparib and other clinically approved PARP inhibitors has already been demonstrated in several experimental models of human diseases, such as neurodegeneration and neuroinflammation, acute hepatitis, skeletal muscle disorders, aging and acute ischemic stroke, protecting, for example, from the deterioration of the blood-brain barrier, restoring the cellular levels of NAD+, improving mitochondrial function and biogenesis and, among other effects, reducing oxidative stress and pro-inflammatory mediators, such as TNF-α, IL1-β, IL-6, and VCAM1. These data demonstrated that repositioning of clinically approved PARP inhibitors may be effective in protecting against hemodynamic dysfunction, metabolic dysfunction, and multiple organ failure in patients with sepsis. Age and gender affect the response to PARP inhibitors, the mechanisms underlying the lack of many protective effects in females and aged animals should be further investigated and be cautiously considered in designing clinical trials.
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Comparative Study
Comparison of Clinical Outcomes with Initial Norepinephrine or Epinephrine for Hemodynamic Support After Return of Spontaneous Circulation.
The optimal vasoactive agent for management of patients with return of spontaneous circulation (ROSC) after cardiac arrest has not yet been identified. The Advanced Cardiac Life Support guidelines recommend initiation of either norepinephrine (NE), epinephrine (EPI), or dopamine (DA) to maintain adequate hemodynamics after ROSC is achieved. The goal of this study is to retrospectively assess the impact of initial vasopressor agent on incidence rate of rearrest, death, or need for additional vasopressor in post-cardiac arrest emergency department (ED) patients. ⋯ These data suggest prospective study of initial vasopressors used for hemodynamic support after ROSC may be warranted. Rates of intra-emergency department refractory shock, rearrest, or death were higher among epinephrine treated patients compared to norepinephrine treated patients in this population. However, inability to control for potential confounding variables in retrospective studies limits the findings. These results are hypothesis generating and further study is warranted.