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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Neutrophil (PMN) influx into the peritoneal cavity in response to bacterial peritonitis is an indispensable aspect of host defense. PMNs also are responsible for the remote organ injury observed after major abdominal infection. The aim of this study was to examine the effect of selectin blockade on PMN migration into the peritoneum and on PMN sequestration in the lungs, early in the course of peritonitis. ⋯ In conclusion, P-selectin mediates PMN influx into the peritoneal cavity, while E- and L-selectins do not appear to play any significant role in the 6 h time period following CLP. Lung PMN sequestration, after CLP, occurred independent of P-, E-, or L-selectin expression. Blockade of P-selectin during peritonitis appears to be potentially deleterious by preventing early PMN influx into the compartment containing the septic focus.
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Tumor necrosis factor (TNF) is released during hepatic ischemia/reperfusion (I/R) and plays an important role in the ensuing neutrophil-mediated lung and liver injury. Since TNF is not a direct neutrophil chemotaxin, we hypothesized that TNF may up-regulate neutrophil adhesion molecules, specifically intercellular adhesion molecule-1 (ICAM-1), following hepatic I/R, and that this molecule then plays an important role in tissue neutrophil influx. Rats underwent 90 min of lobar hepatic ischemia with reperfusion. ⋯ Liver injury was assessed by hepatic neutrophil morphometrics and plasma liver enzymes (alanine aminotransferase). Pretreatment with anti-ICAM-1 antibodies significantly decreased pulmonary capillary permeability, pulmonary myeloperoxidase, hepatic neutrophil influx, and plasma alanine aminotransferase, as compared to animals pretreated with control antibody. These data suggest that TNF is a proximal trigger for pulmonary and hepatic ICAM-1 up-regulation following hepatic ischemia with reperfusion, and that ICAM-1 is important for pulmonary and hepatic neutrophil influx, with the resultant tissue injury, following hepatic I/R.
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The effects of hypertonic (7.5%) saline/6% dextran 70 (HSD) on central and regional hemodynamics were studied during uncontrolled intra-abdominal bleeding in 16 anesthetized pigs. Ultrasonic flow probes were placed proximally and distally to an aortic injury to indicate the incidence and extent of rebleeding after injecting 4 mL kg(-1) (N = 8) and 2.65 mL kg(-1) (N = 8) of HSD 10 min after the vascular injury was induced. The initial aortic bleeding reduced the blood flow rates to 71% of baseline in the skin, 53% in the splanchnic region, 42% in the upper aorta, and 15% in the kidney. ⋯ Five animals in each treatment group died after about 70 min, while the remaining six pigs (38%) survived the 120 min study period. These results suggest that HSD in the recommended dose, and even two-thirds thereof, promotes rebleeding when given shortly after a low energy intra-abdominal aortic injury. The fluid seems to have no beneficial effect on this type of uncontrolled hemorrhage.
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Previous work in our laboratory has demonstrated that HSD is an effective small-volume resuscitation fluid for the treatment of hemorrhagic hypotension, but limitations to its usefulness in severe hemorrhage have not been explored. In the present study, animals (N = 12) were bled from an arterial line at a rate of 1 mL/kg/min until continuously monitored aortic blood flow was reduced to one-half its baseline value, and then they were immediately resuscitated with 7.5% NaCl/6% dextran 70 (hypertonic saline dextran, 4 mL/kg) administered intravenously over 3 min. After recording the maximum improvement in blood pressure, blood samples were obtained and the hemorrhage-resuscitation sequence was repeated until no further measurable increase in cardiac index or blood pressure could be elicited by resuscitation. ⋯ We observed a progressive decrease in base excess from +1.35+/-3.19 (mean +/- standard error) to -12.9+/-2.1 mEq/L even when resuscitation improved oxygen consumption significantly by 95+/-20%. In animals that survived as many as three bleedings and resuscitation, the depletion of buffering capacity of the blood was most predominant, and bicarbonate reached a nadir of 7.62 mEq/L with a base excess of -22.4 mEq/L. It is evident that restoration of perfusion in shock treats only a portion of the physiologic dysfunction, leaving major metabolic derangements uncorrected.
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Fluid resuscitation is the usual therapy for hemorrhagic shock, and frequently consists of the infusion of large volumes of electrolyte solutions. However, to be successful, this therapy should be implemented soon after injury. A new treatment method in which the infusion could be delayed might result in a greater survival rate. ⋯ Whole-body oxygen consumption also increased with TSC, reaching 75% of the normal resting value after about 15 min. This correlates well with the increased survival rates seen, since mortality after hemorrhagic shock is associated with decreased oxygen consumption. These results suggest that the use of TSC could allow for later implementation of fluid resuscitation therapy as well as reducing the volume needed.