Temporal dynamics of pulmonary response to intravenous histamine in dogs: effects of dose and lung volume

Abstract

We measured tracheal pressure (Ptr) and tracheal flow (V) in open-chest anesthetized paralyzed dogs. The lungs were maintained at a fixed volume (initial positive end-expiratory pressure 0.5 kPa) for 80 s while small-amplitude oscillations in V at 1 and 6 Hz were applied simultaneously at the tracheal opening. A bolus of histamine was given intravenously at the start of the oscillation period. The time course of lung elastic recoil pressure (Pel) was obtained by passing a running average over Ptr to smooth out its oscillations. The oscillations themselves were separated into their 1- and 6-Hz components, as were those in V. By fitting models to the 1- and 6-Hz components of Ptr and V by recursive least squares, we obtained time courses of lung resistance at 6 Hz (RL6), dynamic lung elastance at 1 Hz (EL1), and the difference between dynamic lung resistance at 1 and 6 Hz (RL1-RL6). In four dogs we studied the effects of histamine doses of 0.05, 1.0, and 20 mg. We found that Pel increased quickly and plateaued, RL6 continued to increase throughout the oscillation period, and EL1 exhibited features of both Pel and RL6. Furthermore, the ratio of RL1-RL6 to EL1 was qualitatively similar in time course to Pel. We explain these varied time courses in terms of the development of regional ventilation inhomogeneity throughout the lung as the reaction to histamine develops. In four dogs we also studied the effects of reducing the initial positive end-expiratory pressure by 0.25 kPa and found that the changes in RL6, EL1, and RL1-RL6 were greatly magnified, presumably because of the reduced forces of parenchymal interdependence.