PROLONGED METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN DOGS

We studied the effect of prolonged airways obstruction induced by extended cholinergic stimulation in five anesthetized, mechanically ventilated dogs. A continuous intravenous methacholine infusion was utilized to maintain pulmonary resistance (RL) at 200-1500% preinfusion levels for 13-23 h. At maximum RL (18.86±7.74 vs. 2.09±0.18 (mean±SD) cm H2O/ (l/s) preinfusion; P<0.01), dynamic lung compliance (Cdyn) fell from 67.5±14.6 to 32.7±11.6 ml/cm H2O (P<0.005) and arterial partial pressure of oxygen (paO2) fell modestly from 95.8±6.1 Torr preinfusion to 83.2±12.7 Torr (P<0.05). Tachyphylaxis to methacholine developed, requiring increases in infusion rates to maintain elevated RL. Abnormalities in lung function resolved promptly upon termination of the infusion. Two similarly instrumental control animals ventilated for 19 and 25 h without methacholine infusion had no change in RL, Cdyn, or PaO2. Histological examination of the lungs revealed no differences between infused and control animals. In spite of marked increases in RL, prolonged cholinergic stimulation produced only mild changes in gas exchange and no sustained changes in lung function or structure.