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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Comparative Study
Effects of dopamine on systemic and regional blood flow and metabolism in septic and cardiac surgery patients.
Dopamine is used in the clinical setting to support cardiac output and blood pressure and to improve diuresis. Experimental studies suggest that dopamine may reduce splanchnic perfusion and redistribute blood flow locally. To assess the effects of dopamine on splanchnic perfusion, we used dopamine to increase cardiac output by 25% in nine septic patients and 11 patients after cardiac surgery. ⋯ Dobutamine in these patients [6.4 (4.2-9.5) microg x kg(-1) x min(-1)] increased splanchnic blood flow from 1.20 (0.44) L x min(-1) x m(-2) to 1.43 (0.57) L x min(-1) x m(-2) (P = 0.008), while splanchnic oxygen consumption did not change 72 (25) mL x min(-1) x m(-2) vs. 76 (22) mL x min(-1) x m(-2) (not significant)]. The reduction of splanchnic oxygen consumption by dopamine in sepsis suggests an impairment of hepatosplanchnic metabolism despite an increase in regional perfusion. The safety and indications of dopamine use in sepsis should be re-evaluated.
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We have shown previously that bum trauma activates the stress responsive proteins, p38 mitogen-activated protein kinase (MAPK), c-jun NH2-terminal kinase (JNK), and NF-kappaB, and we have shown further that p38 MAPK is an important mediator of cardiomyocyte TNF-alpha secretion and cardiac dysfunction in burn trauma. Since burn trauma causes a rise in circulating catecholamine levels, we hypothesized that this increased sympathetic activity may function as an upstream activator of the p38 MARK pathway in burn trauma. This study determined whether the alpha1-adrenergic receptor ligand phenylephrine could mimic burn trauma activation of p38 MAPK, JNK, and NF-kappaB nuclear translocation; and the effect of the alpha1-adrenergic receptor antagonist prazosin on either phenylephrine or burn-mediated activation of the stress response pathway was examined. ⋯ Burn trauma activated cardiac p38 MAPK/JNK and NF-kappaB, increased TNF-alpha secretion by cardiomyocytes, and impaired cardiac function. Prazosin treatment in burns interrupted the burn-mediated signaling cascade, decreasing TNF-alpha secretion by cardiomyocytes and preventing post-burn cardiac contractile dysfunction. Thus, burn trauma-related sympathetic activity likely activates the stress-responsive cascade, which regulates myocardial TNF-alpha transcription/translation and culminates in cardiac contraction and relaxation defects.
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Comparative Study
Hypertonic saline improves intestinal mucosa barrier function and lung injury after trauma-hemorrhagic shock.
Our objective was to test the hypotheses that small volume hypertonic saline (HTS) resuscitation protects against trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury better than standard volume resuscitation with Ringer's lactate (RL), and that the degree of lung injury correlates with the degree of gut injury after therapy. Male Sprague-Dawley rats were subjected to laparotomy (trauma) and 90 min of T/HS or sham shock (T/SS), and were then resuscitated with RL or 7.5% NaCl solution at an equivalent sodium load. Intestinal and lung injury was assessed at 3 and 24 h after resuscitation. ⋯ Linear regression analysis revealed direct correlations between the percent of injured villi, increased lung permeability, and pulmonary neutrophil sequestration. Resuscitation with HTS ameliorated T/HS-induced gut and lung injury seen with RL resuscitation. These results, together with the direct correlation found between gut and lung injury, suggest that lung injury after T/HS may be mediated by gut injury.
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Virtually of the all recent therapeutic interventions for treating sepsis have failed to improve survival. One potential explanation is that the heterogeneity of the immune response to the septic challenge is such that only a portion of the patients die as a result of excessive inflammation. The clinical trials lacked power because traditional measurements do not accurately identify these patients. ⋯ We tested the value of the IL-6 prediction by surgically resecting the cecum in those animals with IL-6 > 2000 pg/mL, which resulted in a significant improvement in survival. These data demonstrate that IL-6 measured 6 h after injury accurately predicts mortality resulting from experimental sepsis. This measurement may be determined quickly so that therapy may be targeted only to those individuals at significant risk of dying and initiated within sufficient time to be effective.
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Trauma/hemorrhagic shock (T/HS) is associated with significant lung injury, which is mainly due to an inflammatory process, resulting from the local activation and subsequent interaction of endothelial cells and leukocytes. Adhesion molecules expressed by both cell types play a crucial role in the process of neutrophil-mediated endothelial cell injury. We have previously shown that mesenteric lymph duct ligation prevents T/HS-induced lung leukocyte infiltration and endothelial injury, suggesting that inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed following T/HS. ⋯ However, T/HS lymph failed to induce the shedding of E-selectin. In HUVECs treated with T/HS lymph, IL-6 concentrations were higher than HUVECs treated with T/SS lymph. These findings suggest that mesenteric lymph produced after hemorrhagic shock potentiates lung injury by the upregulation of endothelial cell adhesion molecule expression and IL-6 production.