Solute movement across the alveolar-capillary membrane after intratracheally administered bleomycin in rats.
The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Jordana
M
M
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Dolovich
M
M
Irving
L B
LB
Tomioka
M
M
Befus
D
D
Gauldie
J
J
Newhouse
M T
MT
D000042:Absorption; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D007322:Instillation, Drug; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000493:pharmacokinetics; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000378:metabolism; D016284:Technetium Tc 99m Pentetate; D013997:Time Factors; D014132:Trachea
D009942:Organometallic Compounds; D012709:Serum Albumin; D001761:Bleomycin; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate