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 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.
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Severe blunt chest trauma remains an important injury with high morbidity and mortality. However, the associated immunological alterations are poorly understood. Existing big animal models require large-scale settings, are often too expensive, and research products for immunological studies are limited. ⋯ Plasma interleukin-6 and tumor necrosis factor alpha were considerably increased after 180 min. Blunt chest trauma resulted in an early mortality of 10% without subsequent death. On the basis of these findings, this novel mouse model of blunt chest trauma appears suitable for detailed studies on immunological effects of lung contusion.