Biomaterial Database

Amiodarone-induced pulmonary fibrosis in Fischer 344 rats. 1996

P G Reinhart, and Y L Lai, and C G Gairola

Graduate Center for Toxicology, University of Kentucky, Lexington 40546, USA.

Amiodarone is a potent antiarrhythmic agent with a number of side-effects, the most serious being the development of pulmonary toxicity. The purpose of the study was to determine if a single intratracheal instillation of amiodarone would induce pulmonary fibrosis and associated functional changes in rats. Female Fischer 344 rats were given a single intratracheal instillation of 200 microliters containing 1.25 mg amiodarone (n = 9) while the control group received an equivalent volume of sterile water (n = 8). After 6 weeks, pulmonary function tests, lung hydroxyproline measurements and lung histology were performed. The amiodarone-treated animals showed a significant reduction in the coefficient of diffusion (kCO) and a significant increase in lung hydroxyproline levels as compared to the control group. The treated group had abnormal histology including areas of septal thickening with cellular infiltration of the interstitial and alveolar spaces, whereas the control group had normal histology. These observations suggest that the intratracheal instillation route of amiodarone treatment produces a fibrotic response in rats that can be measured physiologically, biochemically and histologically. This model may aid in the elucidation of the mechanism of amiodarone-induced pulmonary toxicity (AIPT)./ABS.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D010991	Plethysmography	Recording of change in the size of a part as modified by the circulation in it.	Plethysmographies
D011650	Pulmonary Alveoli	Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place.	Alveoli, Pulmonary,Alveolus, Pulmonary,Pulmonary Alveolus
D011658	Pulmonary Fibrosis	A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.	Alveolitis, Fibrosing,Idiopathic Diffuse Interstitial Pulmonary Fibrosis,Fibroses, Pulmonary,Fibrosis, Pulmonary,Pulmonary Fibroses,Alveolitides, Fibrosing,Fibrosing Alveolitides,Fibrosing Alveolitis
D011916	Rats, Inbred F344	An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes.	Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D012129	Respiratory Function Tests	Measurement of the various processes involved in the act of respiration: inspiration, expiration, oxygen and carbon dioxide exchange, lung volume and compliance, etc.	Lung Function Tests,Pulmonary Function Tests,Function Test, Pulmonary,Function Tests, Pulmonary,Pulmonary Function Test,Test, Pulmonary Function,Tests, Pulmonary Function,Function Test, Lung,Function Test, Respiratory,Function Tests, Lung,Function Tests, Respiratory,Lung Function Test,Respiratory Function Test,Test, Lung Function,Test, Respiratory Function,Tests, Lung Function,Tests, Respiratory Function
D002248	Carbon Monoxide	Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)	Monoxide, Carbon
D004058	Diffusion	The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT.	Diffusions
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260	Female		Females