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

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.

• Authors: Rio Dumitrascu, Silke Koebrich, Eva Dony, Norbert Weissmann, Rajkumar Savai, Soni S Pullamsetti, Hossein A Ghofrani, Arun Samidurai, Horst Traupe, Werner Seeger, Friedrich Grimminger, Ralph T Schermuly
• Journal: BMC pulmonary medicine (BMC Pulm Med) Vol. 8 Pg. 25 (Dec 17 2008) ISSN: 1471-2466 [Electronic] England
• PMID: 19087359 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• monocrotaline pyrrole
• Monocrotaline

Topics

• Acute Lung Injury (chemically induced, pathology, physiopathology)
• Animals
• Blood Gas Analysis
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hypertension, Pulmonary (chemically induced, pathology, physiopathology)
• Injections, Subcutaneous
• Lung (pathology, physiopathology)
• Lung Compliance
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Monocrotaline (administration & dosage, adverse effects, analogs & derivatives, toxicity)
• Neutrophils (pathology)
• Rats
• Rats, Sprague-Dawley
• Survival Rate