TEMPORAL DYNAMICS OF ACUTE ISOVOLUME BRONCHOCONSTRICTION IN THE RAT

The time course of lung impedance changes after intravenous injection of bronchial agonist have produced significant insights into the mecha nisms of bronchoconstriction in the dog (J. H. T. Bates, A.-M. Lauzon, G. S. Dechman, G. N. Maksym, and T. F. Shuessler. J. Appl. Physiol. 7 6: 616-626, 1994). We studied the time course of acute induced broncho constriction in five anesthetized paralyzed open-chest rats injected i ntravenously with a bolus of methacholine. For the 16 s immediately af ter injection, we held the lung volume constant while applying small-a mplitude flow oscillations at 1.48, 5.45, and 19.69 Hz simultaneously, which provided us with continuous estimates of lung resistance (RL) a nd elastance (EL) at each frequency. This procedure was repeated at in itial lung inflation pressures of 0.2, 0.4, and 0.6 kPa. Both RL and E L increased progressively after methacholine administration; however, the rate of change of EL increased dramatically as frequency was incre ased, whereas RL remained relatively independent of frequency. We inte rpret these findings in terms of a three-compartment model of the rat lung, featuring two parallel alveolar compartments feeding into a cent ral airway compartment. Model simulations support the notions that bot h central airway shunting and regional ventilation inhomogeneity devel oped to a significant degree in our constricted rats. We also found th at the rates of increase in both RL and EL were greatly enhanced as th e initial lung inflation pressure was reduced, in accord with the noti on that parenchymal tethering is an important mechanism limiting the e xtent to which airways can narrow when their smooth muscle is stimulat ed to contract.