Research article

Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury

Rio Dumitrascu¹ , Silke Koebrich¹ , Eva Dony¹ , Norbert Weissmann¹ , Rajkumar Savai^1,3 , Soni S Pullamsetti^1,3 , Hossein A Ghofrani¹ , Arun Samidurai¹ , Horst Traupe² , Werner Seeger^1,3 , Friedrich Grimminger¹ and Ralph T Schermuly^1,3

¹University of Giessen Lung Center (UGLC), Giessen, Germany

²Department of Neuroradiology, Justus-Liebig-University of Giessen, Germany

³Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany

author email corresponding author email

BMC Pulmonary Medicine 2008, 8:25doi:10.1186/1471-2466-8-25

Published:	17 December 2008

Abstract

Background

New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole.

Methods

Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole.

Results

Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight). At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension.

Conclusion

Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.