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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A two-hit model of acid aspiration was used to examine the effect of keratinocyte growth factor (KGF) on chemokine levels and neutrophil recruitment into the lung. Mice were subjected to cecal ligation and puncture and then either KGF or saline, intratracheally (i.t.). Forty-eight hours later, the mice were given i.t. acid. ⋯ However, 8 h after acid aspiration, MIP-2alpha concentrations were significantly lower in the KGF-treated group. The ratio of MIP-2alpha in BAL fluid versus plasma was lower in the KGF group (0.72 +/- 0.28) than in the saline group at 3 h (2.23 +/- 0.93) and also significantly lower in the KGF group (3.02 +/- 0.78) compared with the saline group (6.23 +/- 1.19) at 8 h. In this study, KGF pretreatment after acid aspiration was associated with reduced neutrophil recruitment into the lung and a decrease in MIP-2alpha gradients between BAL fluid and plasma.
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The role of lymphocyte apoptosis in septic shock remains a controversial issue. Using Annexin V and flow cytometry analysis on freshly isolated cells, we evaluated circulating lymphocyte apoptosis in 23 septic shock, 25 sepsis without shock, 7 nonseptic critically ill, and 25 control patients. In patients with sepsis, we compared day 1 lymphocyte apoptosis (i.e., within 3 days of the onset of infection) with that observed 5-7 days after (day 6) according to shock state, mortality, and seventy factors. ⋯ Catecholamines and interleukin 10 levels significantly increased in patients with septic shock, but did not correlate with apoptosis levels. We conclude that lymphocyte apoptosis is rapidly increased in blood of patients in septic shock and that lymphocyte apoptosis leads to a profound and persistent lymphopenia associated with poor outcome. These results suggest that lymphocyte apoptosis is one of the main components of human septic shock immune dysfunction and could be related more to microcirculatory disturbance than to circulating factors.
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Endothelial cell dysfunction occurs during hemorrhagic shock (HS) and persists despite adequate resuscitation (RES) that restores and maintains hemodynamics. We hypothesize that RES from HS with crystalloid solutions alone aggravate the endothelial cell dysfunction. To test this hypothesis, anesthetized nonheparinized rats were monitored for hemodynamics, and the terminal ileum was studied with intravital video microscopy. ⋯ Blood-containing RES regimens preserve and maintain hemodynamics and are associated with the least microvascular dysfunction. Therefore, regimens for RES from HS must contain blood. Endothelial cell dysfunction is not the sole etiologic factor of post-RES microvascular impairment.
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Our objective in this study was to test the hypothesis that priming of neutrophils (PMN) in vivo by trauma-hemorrhagic shock (T/HS) is mediated by factors carried in intestinal lymph that prime PMNs by enhancing their responses to inflammatory mediators. Previous studies have shown that T/HS-induced lung injury is mediated by factors contained in mesenteric lymph and that ligation of the main mesenteric lymph duct (LDL) can prevent T/HS-induced lung injury. Since T/HS-induced lung injury is associated with PMN infiltration, one mechanism underlying this protective effect may be the prevention of PMN priming and activation. ⋯ The results support the concept that trauma and hemorrhagic shock play important additive roles in inflammatory PMN priming. Entry of gut-derived inflammatory products into the circulation via mesenteric lymph seems to play a dominant role in mediating the conversion of physiologic shock insults into immunoinflammatory PMN priming. Shock-induced gut lymph priming enhances PMN responses to many important chemoattractants, most notably the chemokines, and mesenteric lymph duct division effectively reverses such priming to priming levels seen in trauma without shock.
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Platelets are suggested to participate in the pathogenesis of hepatic ischemia-reperfusion (I/R) injury. This study was designed to analyze platelet-endothelial cell interactions in the postischemic mouse liver in vivo and to define the role of endothelial versus platelet P-selectin for these interactions. Platelet-endothelial cell interactions were quantitatively analyzed using intravital fluorescence microscopy after lobar hepatic I/R in C57BL/6 wild-type and P-selectin-deficient mice after infusion of ex vivo rhodamine-6G-labeled wild-type and P-selectin-deficient platelets. ⋯ The present intravital microscopic study provides, for the first time, quantitative analyses of platelet-endothelial cell interactions in the postischemic hepatic microcirculation. Our in vivo data show that endothelial P-selectin is critical for postischemic platelet-endothelial cell interactions within hepatic presinusoidal arterioles and postsinusoidal venules. P-selectin deficiency prevents microvascular injury and apoptosis after warm hepatic I/R.