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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We showed previously that acute blood loss, without resuscitation, caused marked maldistribution of interalveolar perfusion. Because hemorrhage is a known risk factor for the development of lung injury, the goal of our present studies was to determine if there was a correlation between perfusion maldistribution and the subsequent development of lung injury after blood loss. Specifically, we wanted to know if the perfusion maldistribution might be due to microthrombus formation and/or leukocyte sequestration within the pulmonary microcirculation. ⋯ Fibrin-to-leukocyte nearest-neighbor distances remained unchanged (18.1 [SD, 1.1] μm) even as the numbers of both increased with time after blood loss. Our results suggest that soluble fibrinogen polymerized to insoluble fibrin within minutes after acute blood loss, which caused perfusion maldistribution and attracted leukocytes. The development of lung injury after blood loss may be a consequence of leukocyte chemoattraction to fibrin microthrombi that seem to form within minutes after blood loss.
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With more than half of the world population infected, Helicobacter infection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacter infections. Hemorrhage (HS) induces tissue damage that is attenuated by blockade of either complement activation or oxidative stress products. ⋯ The HS-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor-α and nitric oxide in the infected mice. Together, these data indicate that Helicobacter infection modulates the mechanism of HS-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated tumor necrosis factor-α and nitric oxide. These data indicate that chronic low-level infections change the response to trauma and should be considered when designing and administering therapeutics.
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Comparative Study
The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model.
Sepsis is often associated with cholestatic liver dysfunction caused by changes in the expression profile of hepatic bile salt transporters. However, in rodent endotoxin models, the role of ischemic hepatitis caused by liver hypoperfusion cannot be delineated. We hypothesized that hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. ⋯ Bile salt export pump and MRP2 staining were downregulated in septic pigs. During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (Na-taurocholate cotransporting polypeptide) and canalicular efflux (bile salt export pump) of bile salts were downregulated without hemodynamic signs of hepatic hypoperfusion or biochemical signs of cholestasis. In parallel, the basolateral escape transport (MRP4) was markedly upregulated, possibly as an early adaptive response to counteract hepatocellular accumulation of toxic bile acids.