Effects of drug-induced pulmonary phospholipidosis on lung mechanics in rats.
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)
Camus
P
P
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Joshi
U M
UM
Lockard
V G
VG
Petrini
M F
MF
Lentz
D L
DL
Mehendale
H M
HM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002745:Chlorphentermine / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008170:Lung Compliance; D008176:Lung Volume Measurements; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010645:Phentermine / Q000031:analogs & derivatives*; D010743:Phospholipids / Q000032:analysis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012129:Respiratory Function Tests
D010743:Phospholipids; D010645:Phentermine; D002745:Chlorphentermine