Physiologic Responses of Sheep to Two Different Methods of Papain Exposure

Abstract

Human emphysema is a progressive, destructive lung disease that produces morphologic and functional heterogeneity throughout its course. Consequently, the mature form of the disease is described by a broad range of anatomic, radiological, and physiologic patterns. This report describes the development and characterization of a sheep model of emphysema that represents many of the essential features of both homogeneous and heterogeneous emphysema. Emphysema was produced by two different techniques of papain exposure: (1) aerosol (75 IU/kg) given weekly for 4 treatments (HM) or (2) aerosol (75 IU/kg) weekly for 3 treatments following subsegmental intrabronchial instillations, 75 IU (in 10 saline) per lobe in 6 lobes (HT). Dexamethasone (0.06 mg/kg iv) was administered prior intrabronchial instillations only. On computed tomography, the HM group had homogeneous emphysema, the HT group gross nonuniformity of disease and bullae formation. Both groups demonstrated a significant (p < 0.05) increase in residual volume (HM, +38%; HT, +30%). There was a significant increase (p = 0.002) in total lung capacity per kilogram for the HM group. Emphysema had no effect on active or passive chest wall compliances. Diffusion capacity was significantly (p < 0.05) reduced in both groups. Both elastic (p = 0.066) and resistive (p = 0.025) components of impedance were increased in the HT, and airway resistance increased significantly in the HM groups. The HM model demonstrated gas trapping, a characteristic feature of emphysema, but failed to replicate the alterations in lung dynamics observed in the human form of this disease. The HT model demonstrated less static hyperinflation but significant frequency dependence and hence appeared to better represent the dynamic characteristics of human emphysema.

Improvements and additions to the Multiple Path Particle Dosimetry model

“…3a to estimate body weights increases from 0.04647 for the study means regression to 0.069843 when the individual sheep data from Hoffman et al (2003) are added. In contrast, the slope remains relatively the same if body weights are estimated using Stahl (1967) to develop the inverse prediction given by Eq.…”

“…In studies to examine physiologic responses of sheep, FRC and TLC were determined pre-and post-papain exposure in two groups of sheep. One group received papain in a manner designed to produce homogeneous emphysema and the other group was to develop heterogeneous emphysema (Hoffman et al, 2003). However, body weights were not reported.…”

“…Since we are most interested in developing an equation that relates FRC to body weight, we combined the data contained in Mundie et al (1992) and Hoffman et al (2003) and used two different methods to estimate body weight when a value for this variable was not provided. For the first method, Panel A of Mundie et al (1992) was used to estimate the slope of the linear regression and then inverse prediction was used to develop Equation 3a.…”

“…Equations 3a and 3b were also used to estimate the individual body weights for the papain pre-exposure groups of sheep studied by Hoffman et al (2003). As can be seen by the estimated body weight values given in Table 7, the values obtained using Eq.…”

“…A summary of the regression results is given in Table 8. While one would expect the R to increase when more data are used in the regression as reflected by comparing the R for the study means regression to the one for the study means plus the individual values reported by Hoffman et al (2003), a significant change in the slope should not occur if the body weight estimates are accurate. However, Table 8 reveals that the slope using the Mundie et al (1992) data reflected in Eq.…”