Research article
Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury
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* Corresponding author: Ralph T Schermuly Ralph.Schermuly@innere.med.uni-giessen.de
1 University of Giessen Lung Center (UGLC), Giessen, Germany
2 Department of Neuroradiology, Justus-Liebig-University of Giessen, Germany
3 Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany
BMC Pulmonary Medicine 2008, 8:25 doi:10.1186/1471-2466-8-25
Published: 17 December 2008Abstract
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.