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


CONCLUSIONS
Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.
Dumitrascu
Rio
R
University of Giessen Lung Center, Giessen, Germany. rio.dumitrascu@uglc.de
Koebrich
Silke
S
Dony
Eva
E
Weissmann
Norbert
N
Savai
Rajkumar
R
Pullamsetti
Soni S
SS
Ghofrani
Hossein A
HA
Samidurai
Arun
A
Traupe
Horst
H
Seeger
Werner
W
Grimminger
Friedrich
F
Schermuly
Ralph T
RT
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008170:Lung Compliance; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016686:Monocrotaline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000633:toxicity; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
C014114:monocrotaline pyrrole; D016686:Monocrotaline