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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Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. The increased venous resistance accounts for the anaphylactic hypotension in anesthetized dogs. However, the change in peripheral vascular resistances during anaphylactic hypotension in other animals such as rats is not known. ⋯ Hematocrit markedly increased from the baseline values of 43% +/- 1% to 55% +/- 1% at 15 min after antigen. During hemorrhagic shock, Psa decreased in the manner similar to anaphylactic shock; however, Rv did not significantly change, and portal venous pressure decreased. In conclusion, in rat anaphylactic shock, a substantial increase in Rv presumably due to hepatic venoconstriction may decrease venous return, resulting in systemic hypotension.
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There are few blood biomarkers predictive of mortality in adult respiratory distress syndrome (ARDS), and none that currently serve as therapeutic targets. Here, we ask whether a circulating protein angiopoietin 2 (Ang2) correlates with severity of lung injury and mortality in a surgical intensive care unit cohort with acute lung injury (ALI)/ARDS. Tie 2 is a tyrosine kinase receptor expressed on endothelial cells. ⋯ A patient's convalescent (low Ang2) plasma did not disrupt junctional architecture. Although further studies with larger sample sizes will be needed to confirm these results, high Ang2 in critically ill patients with ALI/ARDS is associated with a poor outcome. These data, coupled with our cell culture experiments, suggest that antagonism of Ang2 may provide a future novel therapeutic target for ARDS.
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Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. ⋯ In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.
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Mitochondrial dysfunction is thought to play a role in the pathogenesis of a variety of disease states, including sepsis. An acquired defect in oxidative phosphorylation potentially causes sepsis-induced organ dysfunction. Cytochrome oxidase (CcOX), the terminal oxidase of the respiratory chain, is competitively inhibited early in sepsis and progresses, becoming noncompetitive during the late phase. ⋯ However, cytochrome c injection abrogated this inhibition and restored CcOX kinetic activity to sham values at 48 h. Survival after CLP to 96 h after cytochrome c injection approached 50% compared with only 15% after saline injection. Thus, a single injection of exogenous cytochrome c 24 h post-CLP repletes mitochondrial substrate levels for up to 72 h, restores myocardial COX activity, and significantly improves survival.