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

Volatile anesthetics have a direct relaxant effect on airway smooth muscle, but it is not known whether this effect is similar throughout the bronchial tree. We studied the direct relaxation effect of isoflurane 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 their optimum length. A dose-response curve was obtained for each airway ring with log increments of acetylcholine. Maximum contraction was reached with 10(-2) mol/L of acetylcholine for the proximal airway smooth 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 calculated (1.26 +/- 0.37 x 10(-4) mol/L for proximal airway smooth muscle; 2.12 +/- 1.14 x 10(-5) mol/L for distal airway smooth muscle) and administered to each tissue bath, after which the stabilized response was recorded. A randomly selected dose of isoflurane (1, 2, or 2.6 dog minimum alveolar anesthetic concentration [MAC]) was then administered to each bath and the relaxant responses were recorded. The proximal and distal airways relaxed with increased doses of isoflurane in a dose-related manner. The average distal airway relaxation was three times greater than the proximal airway relaxation at all isoflurane levels. The mechanism 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.