Cui Yong, Nie Hongguang, Ma Hong, Chen Lei, Zhang Lin, Wang Junke, Ji Honglong
Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
J Biomed Biotechnol. 2011;2011:460596. doi: 10.1155/2011/460596. Epub 2011 Oct 3.
Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker), fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity) in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.
氯胺酮是一种广泛用于镇痛镇静的麻醉剂。越来越多的临床证据表明，氯胺酮会导致肺水肿，但其机制尚不清楚。我们在体外测量了氯胺酮对人肺叶肺泡液体清除率的影响。我们的结果表明，气管内滴注氯胺酮显著降低了5%牛血清白蛋白灌洗液的重吸收。在存在氨氯吡咪（一种特异性上皮钠通道阻滞剂）的情况下，液体清除率没有进一步降低，这表明氯胺酮可能会降低与上皮钠通道相关的氨氯吡咪敏感的肺泡液体清除率部分。此外，我们使用全细胞膜片钳模式测量了氯胺酮对A549细胞中氨氯吡咪敏感电流的调节作用。我们的结果表明，氯胺酮以剂量依赖的方式降低了氨氯吡咪敏感的钠离子电流（上皮钠通道活性）。这些数据表明，氯胺酮给药后肺上皮钠通道活性和肺液体清除率的降低可能是导致肺水肿发病机制的关键步骤。
