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 effect of hypertonic saline resuscitation on intestinal damage and the incidence of apoptosis after hemorrhagic shock were investigated. After anesthesia, male BALB/c mice weighing 24-34 g were hemorrhaged to the mean arterial pressure of 40 +/- 5 mmHg for 90 min. Animals were randomly assigned to four groups: 1) resuscitation with 4 mL/kg of 7.5% NaCl (hypertonic saline; HS) + shed blood (SB); 2) resuscitation with two times the volume of shed blood of lactated Ringer's solution (2LR) + SB; 3) sham (catheter only); or 4) control (no treatment). ⋯ In addition, we observed less caspase-3 activation in the small intestine of the HS+SB group compared with the 2LR+SB group at 2 h after resuscitation. The content of HSP40 and HSP70 in the HS+SB group was similar to that in controls, but slightly decreased in the 2LR+SB group. HS resuscitation reduced intestinal damage and apoptosis after hemorrhagic shock, suggesting that HS resuscitation may improve the outcome after hemorrhagic shock by reducing apoptosis and damage to the small intestine.
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Some anesthetics attenuate expression of endotoxin-induced production of proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X) decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the effects of K/X on gut function and gene expression are unknown. ⋯ These data indicate that K/X inhibits some proinflammatory genes and pathophysiologic responses in the serum and stomach during endotoxemia. The effects of K/X appear to inhibit transcriptional events in iNOS expression, which may be dependent on K/X-induced inhibition of early TNF-alpha expression. Furthermore, in rat models of endotoxemia, especially those evaluating the stomach, careful consideration needs to be given if anesthetic combinations with ketamine and/or xylazine are used, as they alter LPS-induced responses.
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Iron metabolism is dysregulated in critically ill patients. A mouse model of dysregulated iron metabolism was used to examine the consequence of iron loading upon sepsis. Mice deleted in the hfe gene (hfe-/-) abnormally accumulate iron in tissue; defects in the human hfe gene are clinically expressed as hemochromatosis. ⋯ Critical care patients often have altered iron metabolism. In clinical practice, critically ill patients may receive iron through direct administration and the transfusion of blood products. Iron therapy may adversely affect the clinical outcome from sepsis.
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The protective effects and roles of AT1-receptor antagonists (AT1-RA) or angiotensin-converting enzyme inhibitors (ACEI) on vascular endothelial cell (EC) injury during hypoxia are not entirely known. Therefore, we investigated these effects and mechanisms in human aortic (HA) EC. DNA fragmentation, Lactate dehydrogenase (LDH) release, and caspase-3 activity were measured in cultured HAEC after exposure to hypoxia in the presence or absence of an AT1-RA (candesartan, CS) and/or an ACEI (temocaprilat, TC). ⋯ This effect was attenuated by the kinin B2 receptor antagonist, HOE 140, and the NOS inhibitor, N-nitro-L-arginine methylester (L-NMMA). Hypoxia activates the pathway leading to apoptosis by enhancing caspase-3 activity. Both CS and TC can ameliorate hypoxia-induced apoptosis in HAEC through inhibiting caspase-3 activation by enhancing ecNOS activity, via the accumulation of BK.
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A mouse model of burn injury demonstrates increasing mortality to an infectious challenge in the form of cecal ligation and puncture (CLP) reaching a peak at 10 days after injury. Because it is widely believed that peritoneal mast cells play an important role in the defense against peritoneal sepsis, we wished to explore the possibility that peritoneal mast cell dysfunction contributed to increased CLP mortality after burn injury. Kit(W-v) C57BL/6 mice, which were shown to lack peritoneal mast cells by cytospin and flow cytometry, and normal littermate control animals were subjected to 25% burn or sham burn injury and 10 days later underwent CLP. ⋯ A study of peritoneal cell populations 24 h after CLP failed to reveal an obvious cause for the difference in CLP survival between the two mast cell-deficient strains. Tumor necrosis factor-alpha (TNF-alpha) measurements in peritoneal fluid showed appreciable amounts of TNF-alpha in the littermate controls of both strains and little in the fluid obtained from the mast cell-deficient animals of both strains. We conclude that peritoneal mast cell dysfunction is unlikely to be a major cause of decreased resistance to peritoneal sepsis in burn-injured animals and that the importance of peritoneal mast cells in combating peritoneal sepsis in the mouse appears to be strain dependent.