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 suspende d in organ baths with physiologic salt solution at 37 degrees C gassed with 95% O-2-5% CO2. Each segment was attached to a fixed glass rod o n 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 t ension and equilibrated for 2-5 h. Human meconium was diluted in physi ologic salt solution (20 g/100 mt) and filtered through gauze. Tension was generated in the segments by adding acetylcholine (10(-6) M) to t he tissue bath. Addition of meconium to the or sn bath (0.1-5 mg/mL) c aused tracheal smooth muscle relaxation in 44% of tracheal segments te sted. Contraction occurred in 8% of tested segments, but only at the i ntermediate and low doses. The amount of relaxation increased signific antly in a concentration-dependent manner. These responses were not af tracheal epithelium, using KCI to generate tone, or by heating meconiu m 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 trach eal 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 prod ucts, by the tracheal epithelium, or a protein. The direct action of m econium on tracheal smooth muscle, which may in part be mediated by a fatty acid, does not appear to contribute significantly to the increas ed airway tone associated with the meconium aspiration syndrome.