Each subject returned on a separate day for the subsequent study. An arterial catheter was inserted into the radial artery of the nondominant arm using an aseptic technique. Spirometric measurements including FRC were measured as described above. In addition, measurements of Rint, minute ventilation (Ve), tidal volume (Vt), respiratory frequency (f), and the anatomic and physiologic dead spaces (VDan and VDphys, respectively) were made while the subject breathed through a one-way valve (Hans-Rudolph, model 1400; dead space 18 ml) on the apparatus shown in Figure 1. Measurements were not made until the subject was judged to be comfortable on the mouthpiece, adjusted to the apparatus, and breathing in a stable state; this usually required 3 to 5 min.
For ventilatory measurements, the flow signal from the pneumo-tachygraph/differential pressure transducer assembly (Hans-Ru-dolph, Inc, model 3800, and Validyne Corp, model MP45, respectively) on the inspiratory side of the valve was electronically integrated to volume and recorded on a four-channel direct pen writing recorder (Gould, Inc, model 2400) at a paper speed of 5 mm/s. From the recording, the minute ventilation (Ve), tidal volume (Vt), and frequency (f) were measured.
Measurements of pulmonary resistance (Rint) were made by the interrupter technique: during inspiration, inspiratory flow was completely occluded by means of the electronically operated shutter at a flow rate of approximately 0.5 L/s; pressure at the mouth was measured via a pressure transducer (Validyne Corp, model MP45), and the mouth pressure and inspiratory flow signals were recorded at a paper speed of 50 mm/s. From the record, Rint was measured as described by Jackson et al. On each occasion, at least seven measurements of Rint were obtained.
The anatomic dead space was measured by a technique described in detail previously. Simultaneous recordings of the expired gas volume and expired CO, concentration were made at paper speed of 25 mm/s. These were digitized (Summagraphics Corp, Digitizer model ID-1-20) using a computer (Zenith Data Systems Corp, model Z-150), and the resultant CO* concentration-volume relationship was displayed on an X-Y plotter (Houston Instruments, Inc). The instrument and sampling delay for CO* was measured before each experiment as described previously. From the CO/volume plot, another computer digitizer routine was used to measure the anatomic dead space. On each occasion, at least five tidal volume breaths were analyzed for measurement of VDan. website
The physiologic dead space (VDphys) was measured by the Enghoff modification of the Bohr technique. Mixed expired Pco2 (PeCOj) was measured, from the distal end of a mixing chamber (Fig 1), simultaneously with the withdrawal of blood from the arterial catheter over a 90-s period. The blood sample was placed on ice and analyzed for Po2, Pco2, and pH in duplicate, within 20 min of sampling, using a calibrated blood gas analyzer (IL, Lexington, MA, model Micro 13). From these data the VDphys was calculated. The measurements of VDan and VDphys were made simultaneously.
The sequence of measurements consisted of baseline measurements of spirometry and FRC, after which the subject breathed on the apparatus, and the resting ventilation and Rint were measured, followed by measurements of resting VDan and VDphys. The subject was then given the predetermined dose of histamine by inhalation and the measurements were repeated at 5,10, and 20 min following the histamine inhalation. Statistical analysis of the data was made by one-way analysis of variance by Newman-Keuls pairwise comparison.
Figure 1. Schematic of apparatus.