Direct effects of meconium on rat tracheal smooth muscle tension in vitro

Increased airway resistance is a component of the meconium aspiration syndrome. Experiments were done to determine whether meconium can have a direct affect on tracheal smooth muscle tension. Tracheal segments (4-5 mm long) were isolated from male Sprague-Dawley rats and suspended in organ baths with physiologic salt solution at 37 degrees C gassed with 95% O2-5% CO2. Each segment was attached to a fixed glass rod on one side and to a force displacement transducer on the other side to measure transverse tension. The segments were stretched to 1.5 g of tension and equilibrated for 2-5 h. Human meconium was diluted in physiologic salt solution (20 g/100 mL) and filtered through gauze. Tension was generated in the segments by adding acetylcholine (10(-6) M) to the tissue bath. Addition of meconium to the organ bath (0.1-5 mg/mL) caused tracheal smooth muscle relaxation in 44% of tracheal segments tested. Contraction occurred in 8% of tested segments, but only at the intermediate and low doses. The amount of relaxation increased significantly in a concentration-dependent manner. These responses were not affected by pretreating segments with indomethacin, removing the tracheal epithelium, using KCl to generate tone, or by heating meconium above 60 degrees C for 1 h. Addition of oleic acid to the organ bath (3.5 x 10(-6) to 3.5 x 10(-4) M) caused concentration-dependent tracheal smooth muscle responses (with relaxation predominating at 3.5 x 10(-4) M and contraction predominating at 3.5 x 10(-6) M). These results suggest that meconium can cause tracheal smooth muscle relaxation by a mechanism that does not appear to be mediated by cyclooxygenase products, by the tracheal epithelium, or a protein. The direct action of meconium on tracheal smooth muscle, which may in part be mediated by a fatty acid, does not appear to contribute significantly to the increased airway tone associated with the meconium aspiration syndrome.