Lung

, Volume 182, Issue 2, pp 119–134

Bronchiolitis Obliterans Induced by Intratracheal Papaverine: A Novel Animal Model

Article

DOI: 10.1007/s00408-003-1049-3

Cite this article as:
Svetlecic, J., Molteni, A. & Herndon, B. Lung (2004) 182: 119. doi:10.1007/s00408-003-1049-3

Abstract

Constrictive bronchiolitis obliterans (CBO), a highly fatal syndrome seen following toxicant exposure and lung transplantation, is in need of mechanistic study. This report creates an animal model of toxicant induced CBO, validates its pathology and suggests a physiologic mechanism for its origin. Papaverine, the alkaloid in Sauropus plants and responsible for human toxicant-induced CBO, was used to create the rat model. A mini-osmotic pump delivered papaverine intratracheally for up to 28 days (0.25 µL/hr, totaling 6.4 mg). Bronchoalveolar lavage (BAL) was measured. Lung tissue was evaluated for signs of CBO (H&E and Trichrome staining). Cytokines deregulated in human CBO were also measured (TGF-β and eNOS). Peribronchial inflammation, extensive denudation and destruction of bronchial mucosa, as well as increased peribronchial collagen (all classic signs of CBO) were observed as early as 7 days in papaverine treated animals, with more extensive damage after 28 days. Significant elevations of TGF-β and eNOS were seen in lung homogenates. Our toxicant induced model of CBO via a novel delivery method of intratracheal papaverine accurately reproduces pathology and cytokine profiles of human CBO. Papaverine has potential for producing CBO by multiple routes. This model introduces a vehicle for both understanding and development of innovative treatment for CBO.

Keywords

Bronchiolitis obliterans Animal model Toxicant-induced Sauropus TGF-β eNOS Lung 

Copyright information

© Springer-Verlag New York Inc. 2004

Authors and Affiliations

  1. 1.Pulmonary Research Laboratory, Gold 5 Lab of Pulmonary ResearchUniversity of Missouri-Kansas City School of Medicine, M5-210, 2411 Holmes St., Kansas City, Missouri 64108USA
  2. 2.Department of PathologyUniversity of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64108USA