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
-
Zinc ions (Zn) are essential for tissue repair following injury or stress. We hypothesize that during such stresses Zn is redistributed to labile pools in plasma components. Here we tested this hypothesis using a novel assay to monitor labile Zn in plasma in hemorrhagic shock. ⋯ In the high-molecular-weight pool, marked and significant impairment of binding was noted throughout all time periods following the shock period in the S group. Such changes were observed in the SC group of less intensity and duration. These experiments suggest that shock alters affinity of plasma proteins for Zn, promoting delivery to peripheral tissues during periods of increased Zn utilization.
-
Cardiovascular collapse is the major factor contributing to the mortality of trauma-hemorrhage (T-H) patients. Toll-like receptors (TLRs) play a critical role in T-H-induced cardiac dysfunction. This study evaluated the role of TLR9 agonist, CpG-oligodeoxynucleotide (ODN) 1826, in cardiac functional recovery after T-H. ⋯ Our data suggest that CpG-ODN significantly attenuates T-H-induced cardiac dysfunction. The mechanisms involve activation of both PI3K/Akt and ERK signaling pathways. The TLR9 agonist, CpG-ODN 1826, may provide a novel treatment strategy for preventing or managing cardiac dysfunction and enhancing recovery in T-H patients.
-
Shen-Fu injection (SFI) following cardiac arrest exhibits cardioprotective effects, but its effect on myocardial dysfunction, a critical issue following resuscitation, is unclear. This study sought to examine whether SFI reduces postresuscitation myocardial dysfunction in a porcine model of cardiac arrest by modulating apoptosis. After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized divided into three groups, which received central venous injection of either Shen-Fu (SFI group; 1.0 mL/kg), epinephrine (EP group; 0.02 mg/kg), or saline (SA group). ⋯ Caspase 3-mediated apoptosis occurs following myocardial injury after cardiopulmonary resuscitation in pigs. Shen-Fu injection decreased myocardial injury; improved myocardial ultrastructure; inhibited Bcl-2, Bax, and caspase 3 expression; and reduced myocardial apoptosis. Therefore, SFI could significantly attenuate postresuscitation myocardial dysfunction by modulating apoptosis.
-
Human C1 inhibitor (C1INH) prevents endotoxin shock via a direct interaction with Gram-negative bacterial lipopolysaccharide (LPS) and improves survival in animal models of sepsis. In this report, we further characterize the interaction of C1INH with LPS and whole live bacteria. We investigate C1INH interactions with LPS from five different strains of Gram-negative enteric bacteria known to participate in the pathogenesis of human sepsis. ⋯ The binding of both native and reactive center-cleaved, inactive C1INH results in inhibition of LPS-induced proinflammatory cytokine production. Furthermore, we demonstrate the ability of C1INH to bind at the surface of only a restricted number of whole live Gram-negative bacteria as well as mutant bacteria expressing a truncated LPS lacking the O-antigen. These data reveal the interaction of C1INH with a wide range of enteric bacterial LPS and strongly suggest that the interaction between C1INH and the surface of Gram-negative microorganisms is determined by the length of the polysaccharide chain of the endotoxin molecule.
-
Randomized Controlled Trial
Continuous enteral and parenteral feeding each reduces heart rate variability but differentially influences monocyte gene expression in humans.
Enteral (EN) or parenteral (PN) nutrition is used to support critically ill patients until oral feeding resumes. Enteral nutrition is assumed preferable to PN, but the differential influence on immune function is not well defined. Autonomic nervous activity is known to influence innate immune responses, and we hypothesized that EN and PN could influence both autonomic signaling and gene activation in peripheral blood monocytes (PBMs). ⋯ However, PN feeding had a much greater influence on PBM gene expression compared with baseline than EN, including genes important to innate immunity. Continuous EN and PN are both associated with decreasing vagal tone over time, yet contribute differently to PBM gene expression, in humans. These preliminary findings support assumptions that PN imposes a systemic inflammatory risk but also imply that continuous feeding, independent of route, may impart additional risk through different mechanisms.