How mode of stimulus affects the relative contribution of elastance and hysteresivity to changes in lung tissue resistance

Challenges with high concentrations of constrictor agonist delivered by intravenous vs. aerosol result in different modifications of the mechanical properties of lung tissues. We questioned whether low doses of a smooth muscle agonist administered via different routes (aerosol, iv bolus, iv continuous infusion) or an increase in positive end-expiratory pressure (PEEP) would result in different mechanical perturbations of lung tissues. Tracheal and alveolar pressures and flow were measured in open-chest mechanically ventilated (frequency 1 Hz, tidal volume 10 ml/kg, PEEP 4 cmH₂O) rats under baseline conditions and after administration of low doses of methacholine or after increases in PEEP. We calculated lung elastance (EL), lung resistance, and tissue resistance (Rti) by fitting the equation of motion to changes in tracheal and alveolar pressures. Airway resistance and hysteresivity (η) were derived from the above measurements. For comparable increases in Rti, the aerosol and PEEP groups showed large increases in EL with a decrease in η, whereas the two intravenous groups showed large increases in η with smaller increases in EL. The largest contribution of η to the overall increase in Rti was seen in the intravenous bolus group. When induced changes in EL vs. induced changes in η were plotted, different relationships were found for the four groups. We conclude that despite similar increases in Rti a different kind of mechanical perturbation occurred in the lung tissues that depended on the nature of the stimulus.