The Journal of surgical research
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Lactic acidosis and increased production of CO(2) are common in septic shock. Presumably, both acidosis and CO(2) enhance the release of oxygen from hemoglobin. The purpose of this study was to assess the relationship of oxygen utilization, CO(2) production, acidosis, and hemoglobin oxygen (Hgb-O(2)) dissociation with progressive severity of sepsis to shock. ⋯ This study demonstrates that increased oxygen extraction in severe sepsis is related to a fall in tissue oxygen availability and not related to any allosteric change in Hgb-O(2) dissociation. Therefore, acidosis and hypercapnia do not have a demonstrable effect on altering oxygen availability during sepsis.
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Ketamine and xylazine (K/X) are commonly used in combination as an anesthetic agent in experimental animal models. We previously noted that K/X attenuated lipopolysaccharide (LPS)-induced liver injury, gastric stasis, and reduced symptoms of endotoxemia. Because ketamine attenuates expression of several proinflammatory genes, we examined the effects of K/X on inducible nitric oxide synthase (iNOS), which has been implicated in endotoxin-induced tissue injury. ⋯ Furthermore, K/X almost completely blunted LPS-induced expression of iNOS in stomach, duodenum, jejunum, and colon. These data indicate that K/X attenuates LPS-induced upregulation of iNOS in a variety of tissues. Furthermore, in rat models studying the in vivo effects of endotoxin, especially those evaluating the gastrointestinal system, careful consideration needs to be given if the anesthetic combination of K/X is used, as it alters LPS-induced expression of iNOS, an important pathophysiologic mediator in endotoxemia.