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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The splanchnic area is of considerable interest in different types of shock. To characterize the metabolic changes in the splanchnic region in response to different types of shock we used a model where shock-induced metabolic changes in the splanchnic region were studied by the use of intravasal microdialysis. 23 anesthetized domestic pigs were randomized into four groups: Group I, serving as controls (n = 5); Group II, mesenteric ischemia for 180 followed by 120 min of reperfusion (n = 5); Group III, endotoxin shock for 5 h (n = 5); and Group IV, hemorrhagic shock for 180 min followed by re-transfusion of shed blood (n = 8). Microdialysis catheters were placed in the left femoral artery, portal vein and a small ileal mesenteric vein. ⋯ Studying the lactate/pyruvate ratio may provide additional information when interpreting increased blood lactate levels. In addition glycerol may prove to be a useful marker of splanchnic ischemia. Intravasal microdialysis represents a potentially useful method for monitoring regional metabolic events.
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Comparative Study
Cecal ligation and puncture versus colon ascendens stent peritonitis: two distinct animal models for polymicrobial sepsis.
Colon ascendens stent peritonitis (CASP) and cecal ligation and puncture (CLP), two animal models designed to closely mimic the clinical course of intra-abdominal sepsis, were compared. In the past, immunomodulatory therapies developed in animal studies failed to be successful in humans. As a consequence, the established animal sepsis models were criticized. ⋯ Twenty-four hours after CLP surgery, the ligated cecum was covered by adhesive small bowel loops, whereas in CASP mice, the intestinal leakage was then still present. The CASP model mimics closely the clinical course of diffuse peritonitis with early and steadily increasing systemic infection and inflammation (systemic inflammatory response syndrome). In contrast, CLP reveals a model of intra-abdominal abscess formation with sustained and minor signs of systemic inflammation.
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Sepsis-induced acute lung injury is still associated with high morbidity and mortality. The pathophysiology is complex, and markers of injury include increased extravascular lung water. To evaluate the effects of the novel dual endothelin receptor antagonist tezosentan on endotoxin-induced changes in extravascular lung water and gas exchange, 16 pigs were anaesthetized and catheterized. ⋯ Tezosentan had a marked effect on the endotoxin-induced increase in extravascular lung water that was reduced to levels observed in nonendotoxemic sham animals. These results suggest that endothelin is involved in endotoxin-induced lung injury and the development of pulmonary edema. Dual endothelin receptor antagonism may be of value in the treatment of sepsis-related acute lung injury.
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Chronic ethanol use preceding severe trauma and hemorrhagic shock (HS) is associated with an increased incidence of multiorgan failure (MOF) and death; however, the molecular basis for this increased susceptibility is unknown. We previously demonstrated that production of interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF), mediated by nuclear factor-kappa B (NF-kappa B), each make essential contributions to organ injury and inflammation in a rodent model of controlled HS, and we proposed in this study to examine the hypothesis that the increased susceptibility to MOF after shock/trauma in the setting of chronic ethanol use is due to an exaggerated activation of NF-kappa B and production of these proinflammatory cytokines. ⋯ The increased liver injury in the ethanol-fed HS rats was accompanied by a 70% increase in liver NF-kappa B activation (P < 0.05), a 3- to 5-fold increase in hepatocyte and Kupffer cell production of IL-6 and G-CSF (P < 0.05 for each), and a 2-fold increase in neutrophil infiltration (P < 0.005) compared with the control diet-fed HS rats. Thus, increased susceptibility to HS-induced liver injury in the setting of chronic ethanol use may be mediated, at least in part, by increased NF-kappa B activation resulting in increased local production of IL-6 and G-CSF and increased infiltration of neutrophils, which can damage liver cells directly and contribute to impaired sinusoidal blood flow.
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The regulation of compensatory hemodynamic, inflammatory, and metabolic counter-regulatory responses to traumatic injury (trauma/hemorrhage [tx/hem]) and subsequent inflammatory challenges during the post-tx/hem period relies on balanced activation of neuroendocrine and opioid pathways. Pharmacological interventions during the rescue period as well as during the early post-tx/hem period that target these regulatory pathways can potentially affect the activation or efficacy of compensatory mechanisms. Their impact on mechanisms involved in these responses has not been well defined. ⋯ Morphine attenuated LPS-induced lung and spleen TNF expression, whereas ketamine enhanced spleen TNF expression but did not alter lung responses. Subsequent studies demonstrated that the morphine-induced impairment of the response was not due to altered cytokine responses during the early post-tx/hem period but that they could be restored and 24 h mortality could be reduced by increasing the volume of LRFR (2-fold). These results indicate that morphine and ketamine analgesia compromise the hemodynamic and host defense responses after tx/hem, directly affecting mortality and morbidity during the recovery period.