title: Ketamine inhibits lung fluid clearance through reducing alveolar sodium transport.
abstract: 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.
authors: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. cynhg@sina.com
authors: Yong
authors: Y
authors: Cui
authors: Hongguang
authors: H
authors: Nie
authors: Hong
authors: H
authors: Ma
authors: Lei
authors: L
authors: Chen
authors: Lin
authors: L
authors: Zhang
authors: Junke
authors: J
authors: Wang
authors: Honglong
authors: H
authors: Ji
mesh_terms: D000042:Absorption; D000368:Aged; D000584:Amiloride / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: D000778:Anesthetics, Dissociative; D026941:Sodium Channel Blockers; D012710:Serum Albumin, Bovine; D007649:Ketamine; D000584:Amiloride; D012964:Sodium