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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Acute rejection (AR) and acceptance of allograft after liver transplantation (LTx) remain critical issues that need addressing to improve prognosis. We therefore performed rat orthotopic LTx and proteomic analyses to screen for immune response-related biomarkers in sera. Markers identified were validated at the mRNA and/or protein levels, and the molecules of interest were functionally explored. ⋯ Interferon-γ, IL-10, and IL-17 proteins in the supernatant of HPX-stimulated lymphocytes were significantly altered in keeping with the mRNA level. Our data facilitated the generation of a proteomic profile to enhance the understanding of rat liver AR. In view of finding that the HPX serum level is negatively associated with the severity of AR of rat liver allograft, we propose that in vitro treatment with HPX regulates cytokine expression in rat lymphocytes.
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Short-term prognostic factors in patients with cardiogenic shock (CS) have previously been established using only hemodynamic parameters without taking into account classic intensive care unit (ICU) severity score or organ failure/support. The aim of this study was to assess early predictors of in-hospital mortality of a monocentric cohort of patients with ST-elevation myocardial infarction complicated by early CS. We retrospectively studied 85 consecutive patients with CS complicating acute myocardial infarction and Thrombolysis in Myocardial Infarction flow grade 3 after percutaneous coronary revascularization. ⋯ The 28-day mortality rate was 39%. Under multivariate analysis, initial cardiac power index, mean arterial pressure of less than 75 mmHg at hour 6 of ICU management, and Simplified Acute Physiology Score II were independent predictive factors of in-hospital mortality. In conclusion, parameters directly related to cardiac performance and vascular response to vasopressors and admission Simplified Acute Physiology Score II are strong predictors of in-hospital mortality.
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Cardiac dysfunction is a major consequence that contributes to the high mortality of trauma-hemorrhage (TH) patients. Recent evidence suggests that innate immune and inflammatory responses mediated by Toll-like receptors (TLRs) play a critical role in the pathophysiologic mechanisms of acute organ dysfunction during TH. This study investigated the role of TLR4 in cardiac dysfunction following TH. ⋯ The data indicate that TLR4 plays a central role in TH-induced cardiac dysfunction. Toll-like receptor 4 deficiency or TLR4 inhibition attenuated cardiac dysfunction following TH, which may involve activation of the phosphoinositide 3-kinase/Akt signaling and decrease in nuclear factor κB-binding activity. Toll-like receptor 4 antagonism may be a new and novel approach for the treatment and management of cardiac dysfunction in TH patients.
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Comparative Study
Establishment of Methods for Performing Thrombelastography and Calibrated Automated Thrombography in Rats.
Rodent models of hemorrhagic shock are paramount to our understanding of the pathophysiology of this disease, the effects on coagulation and in exploring the utility of resuscitative methods for managing patients in shock. These models usually require serial blood sampling during experimentation. The lack of standardized practices for these experimental models has resulted in technical variability, discordance in the literature, and incomparable results on blood coagulation analysis between researchers, hindering substantial progress in the field of hemorrhagic shock. ⋯ Blood was collected from anesthetized rats via cardiac puncture or femoral artery catheterization and hemostatic potential analyzed by thrombelastography and calibrated automated thrombography. Our data show that blood collected via cardiac puncture demonstrated hypercoagulability as indicated by faster rates of clot formation and thrombin generation, increased overall clot strength, and a greater thrombin-generating capacity when compared with blood collected via femoral artery catheter. We conclude that blood collection methods have a profound effect on hemostatic potential, and standardization of these practices is necessary to define the effects of shock on coagulation in rodents.