Anesthesiology
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Treatment of postsurgical pain is a major use of analgesics, particularly after abdominal surgery. Analgesics display a number of limiting side effects, including sedation, cognitive impairment, and ileus. Although several postoperative rodent models have been developed, these models do not address these concerns. ⋯ The current model is consistent with behavioral aspects of postoperative pain seen clinically. The effects of morphine and ketorolac alone and in combination were consistent with the reported analgesic efficacy and occurrence of side effects found with these agents clinically.
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Although it does not suppress movement in response to noxious stimuli, the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also known as 2N) does cause amnesia and seizures. These occur at 0.48 and 1.3 times, respectively, the concentrations that are predicted from its lipid solubility to cause immobility. The molecular and cellular basis of these effects is not known. The ionotropic gamma-aminobutyric acid type A (GABAA) receptor is modulated strongly by anesthetics, and it plays an important role in many seizure models. Also, the hippocampus is a structure central to the formation of memory and is susceptible to seizure generation. The authors therefore investigated the effect of F6 on GABAA receptor- mediated inhibition in hippocampal neurons. ⋯ At concentrations that bracket the in vivo amnestic and seizure-inducing range, F6 has no discernible effect on fast synaptic GABAA receptors in hippocampal CA1 pyramidal neurons. Synaptic GABAA receptors sharply discriminate between volatile anesthetics and a prototype nonimmobilizer. Similar in vivo effects of anesthetics and nonimmobilizers may be mediated by different cellular mechanisms.
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The effect of nitric oxide synthase inhibitor on acute lung injury remains controversial. The current study was designed to examine effects of a newly synthesized and selective inducible nitric oxide synthase inhibitor, ONO1714, on endotoxin-induced lung injury in unanesthetized sheep. ⋯ These findings suggest that nitric oxide release by the inducible nitric oxide synthase pathway partially contributes to the increased permeability of pulmonary edema and decreased oxygenation during endotoxemia in sheep.