Halothane inhibition of ion transport of the tracheal epithelium. A possible mechanism for anesthetic-induced impairment of mucociliary clearance.
Significant depression of mucociliary function occurs during general anesthesia. One possible mechanism to account for this effect is a change in ion and water transport across airway epithelium. To determine if anesthetics alter epithelial cell function, we used electrophysiologic techniques to measure the effects of halothane on ion transport of in vitro canine tracheal epithelial. Epithelial tissues were mounted in an Ussing chamber and the short-circuit current (Isc) (a measure of active ion transport) and transepithelial resistance were determined in the absence and presence of halothane. Halothane induced a rapid and reversible decrease in Isc that was dose-dependent. Four percent halothane reversibly decreased Isc from 90 +/- 11 to 39 +/- 6 microA/cm2 (n = 12; P = 0.001) and increased transepithelial resistance. Isoproterenol is a well-known activator of chloride secretion that acts via beta-adrenergic receptors and cyclic adenosine monophosphate (cAMP). Pretreatment with isoproterenol or dibutyryl cAMP (a cell permeable analogue of cAMP) increased the percent inhibition of Isc by 4% halothane. These effects are consistent with preferential inhibition of chloride secretion by halothane but rule out a primary action of halothane on the beta-adrenergic system. In the presence of indomethacin, which eliminates the contribution of chloride secretion to Isc, 4% halothane induced a much smaller but still significant inhibition. This suggests that sodium absorption is also affected. We conclude that halothane significantly decreases ion and water transport in canine epithelia and that impaired fluid secretion may contribute to decreased mucous clearance in the perioperative period.
Pizov
R
R
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Takahashi
M
M
Hirshman
C A
CA
Croxton
T
T
D000818:Animals; D003864:Depression, Chemical; D004285:Dogs; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D016623:Ion Pumps / Q000187:drug effects* / Q000502:physiology; D009079:Mucociliary Clearance / Q000187:drug effects* / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D016623:Ion Pumps; D006221:Halothane