Journal of Applied Physiology, Vol 66, Issue 5 2437-2445, Copyright © 1989 by American Physiological Society
Effects of drug-induced pulmonary phospholipidosis on lung mechanics in rats
P. Camus, U. M. Joshi, V. G. Lockard, M. F. Petrini, D. L. Lentz and H. M. Mehendale
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Chronic administration of amphiphilic drugs to rats induces pulmonary
phospholipidosis (P), a disease characterized by accumulation of
phospholipids and large foamy macrophages in alveolar spaces. We
investigated whether P induced by chlorphentermine (CPH) causes changes in
lung volumes and mechanics in this species. Groups of rats were fed CPH (50
mg.kg-1.day-1) for 1, 2, 3, 5, 9, and 14 wk. After each treatment period,
lung volumes and mechanics were studied in the anesthetized, paralyzed,
supine rat. Partial pressure-volume (PV) curves were developed at 3 and 6
ml above functional residual capacity (FRC; PV3, PV6), followed by maximal
[up to total lung capacity (TLC)] PV curves. FRC was determined by saline
displacement. Lungs were then fixed for histopathological examination. A
subgroup of animals was allowed a recovery period of 6 wk, after the 9 wk
of CPH administration. Pair-fed rats served as controls (CTR) at each time
point. Lung weight increased in CPH-treated (CPH-T) rats from 1.5 +/- 0.2
(SD) g at week 1 to 5.8 +/- 1.4 g at week 14, reflecting the development of
P. TLC, FRC, transpulmonary pressure at FRC, the shape of maximal PV
curves, and static expiratory lung compliance computed from maximal PV data
points did not change in CPH-T rats. However, partial PV curves of CPH-T
lungs (particularly PV3) were shifted downward and to the right of those of
CTR at 2, 3, 5, and 9 wk, indicating increased recoil pressure in
phospholipidotic lungs at these time points.(ABSTRACT TRUNCATED AT 250
WORDS)
