TOPOGRAPHICAL DIFFERENCES IN THE DIRECT EFFECTS OF ISOFLURANE ON AIRWAY SMOOTH-MUSCLE

Volatile anesthetics have a direct relaxant effect on airway smooth mu scle, but it is not known whether this effect is similar throughout th e bronchial tree. We studied the direct relaxation effect of isofluran e on isolated proximal (outer diameter [OD] 4-6 mm) and distal (OD 0.7 -1.5 mm) canine airways precontracted with acetylcholine. Proximal and distal airway rings were suspended in tissue baths and stretched to t heir optimum length. A dose-response curve was obtained for each airwa y ring with log increments of acetylcholine. Maximum contraction was r eached with 10(-2) mol/L of acetylcholine for the proximal airway smoo th muscle (7.0 +/- 0.3 g of tension) and 10(-3) mol/L of acetylcholine for the distal airway smooth muscle (2.3 +/- 0.1 g of tension). Based on the dose-response curve, the ED(50) of acetylcholine was calculate d (1.26 +/- 0.37 x 10(-4) mol/L for proximal airway smooth muscle; 2.1 2 +/- 1.14 x 10(-5) mol/L for distal airway smooth muscle) and adminis tered to each tissue bath, after which the stabilized response was rec orded. A randomly selected dose of isoflurane (1, 2, or 2.6 dog minimu m alveolar anesthetic concentration [MAC]) was then administered to ea ch bath and the relaxant responses were recorded. The proximal and dis tal airways relaxed with increased doses of isoflurane in a dose-relat ed manner. The average distal airway relaxation was three times greate r than the proximal airway relaxation at all isoflurane levels. The me chanism of this differential response is not known, but may be due to an epithelium-dependent effect, sensitivity of contractile elements to Ca2+; and/or differences in ionic fluxes.