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
-
In septic shock (SS), dysfunction of many organ systems develops during the course of the illness, although the mechanisms are not clear. In earlier studies, we reported that lysozyme-c (Lzm-S), a protein that is released from leukocytes and macrophages, was a mediator of the myocardial depression and vasodilation that develop in a canine model of Pseudomonas aeruginosa SS. Whereas both of these effects of Lzm-S are dependent on its ability to intrinsically generate hydrogen peroxide, we subsequently showed that Lzm-S can also deposit within the vascular smooth muscle layer of the systemic arteries in this model. ⋯ In the in vivo model, Lzm-S accumulated in the kidney and the superior mesenteric artery. In a canine renal epithelial preparation, we further showed that Lzm-S can be taken up by the renal tubules to activate inflammatory pathways. We conclude that Lzm-S can deposit in the systemic vasculature and kidneys in SS, where this deposition could lead to acute organ dysfunction.
-
Malnutrition is a risk factor for infection, compromising immune response. Glutamine (Gln) protects the lungs and distal organs in well-nourished septic and nonseptic conditions; however, no study to date has analyzed the effects of Gln in the presence of sepsis and malnutrition. In the present work, we tested the hypothesis that early therapy with intravenous Gln prevents lung and distal organ damage in septic malnourished rats. ⋯ In malnutrition-cecal ligation and puncture rats, Gln therapy yielded (a) reduced static lung elastance, alveolar collapse, inflammation (neutrophil infiltration, interleukin 6), and collagen deposition; (b) repair of types I and II epithelial cells; (c) no significant changes in heat shock protein 70 expression or heat shock factor 1 phosphorylation; (d) a greater number of M1 and M2 macrophages in lung tissue; and (e) less apoptosis in the lung, kidney, small intestine, and liver. In conclusion, early therapy with intravenous Gln reduced inflammation, fibrosis, and apoptosis, minimizing lung and distal organ injury, in septic malnourished rats. These beneficial effects may be associated with macrophage activation in the lung.
-
Intra-abdominal hypertension/abdominal compartment syndrome (IAH/ACS) is a well-recognized entity among surgical subspecialties. Nevertheless, it has been proven to be present in the medical critically ill population. Prospective and retrospective observational studies have found medical patients with IAH/ACS to be associated with death in the intensive care unit and other poor outcomes. ⋯ Furthermore, they are less likely to receive treatment targeted at lowering intra-abdominal pressure. Medical treatment of IAH/ACS has not been demonstrated to be specifically effective to avoid decompressive surgery. Identifying medical patients at risk of IAH represents an underresearched area for which training in measurement of abdominal pressure surrogates, awareness of its prevalence, and prevention and treatment of such condition could further improve outcomes in critically ill medical patients.
-
Comparative Study Clinical Trial
Racial Differences in Vasopressor Requirements For Septic Shock.
The objective of this study was to compare vasopressor requirements between African American (AA) patients and white patients in septic shock. ⋯ African American patients with septic shock were treated with higher doses of NE and required longer duration of NE administration compared with white patients.
-
The accumulation of autophagosomes in the terminal step of the autophagic process has recently emerged as a potentially maladaptive process in the septic heart and lung. However, the role of autophagy in the septic liver has not been ascertained. This study was investigated by first examining the entire sequence of the autophagic process in the liver of septic mice. ⋯ However, disruption of autophagosomal clearance with chloroquine abolished the above protective effects in CBZ-treated CLP mice. 3-Methyladenine, which resulted in inhibition of the autophagosomal formation, did not show any above beneficial effects in CLP mice. Impaired autophagosome-lysome fusion resulting in incomplete activation of autophagy may contribute to sepsis-induced liver injury. Treatment with CBZ may serve a protective role in the septic liver, possibly through the effect of complete activation of autophagic process.