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

Abstract

BackgroundNew 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.MethodsSurvival 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.ResultsMonocrotaline 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.ConclusionMonocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.

Schistosomiasis-Induced Experimental Pulmonary Hypertension

“…In a distinct mouse model of Th-2-driven inflammation, inhaled aspergillus also resulted in RELM-␣ up-regulation and vascular remodeling with no evidence of chronic PH, yet mild increases in right ventricular pressures were revealed only when sensitized lungs were challenged with acute hypoxia. 25 Our finding of PH in S. mansoni-infected mice lacking IL-13Ra2 suggests that enhanced IL-13 signaling is sufficient to cause PH in this model. This up-regulation occurred in the absence of a significant increase in total lung IL-13 levels as compared with wild-type mice with a less pronounced phenotype.…”

Aspirin Attenuates Pulmonary Arterial Hypertension in Rats by Reducing Plasma 5-Hydroxytryptamine Levels

“…The model of pulmonary hypertension in MCT-injected rats reproduced the neointimal proliferation and vascular occlusion by smooth muscle cells that occurs in human PAH. MCT undergoes hepatic metabolism in rats into monocrotaline pyrrole, which causes endothelial injury in the pulmonary vasculature with subsequent remodeling of the precapillary vessels, progressive pulmonary hypertension, and compensatory right-heart hypertrophy [19]. We successfully created the model by inducing PAH with MCT (50 mg/kg, i.p.).…”

The monocrotaline model of pulmonary hypertension in perspective

“…However, plexiform-like vascular lesions have not been described after a "single hit" of MCT alone, while other pathological changes have been reported as a consequence of MCT exposure. MCT not only injures the pulmonary arteries but also induces alveolar edema, alveolar septal cell hyperplasia, and occlusion of pulmonary veins (20,37). MCT-induced interstitial pulmonary fibrosis has also been described in mice (with variable doses and time points) (20,29).…”

“…MCT not only injures the pulmonary arteries but also induces alveolar edema, alveolar septal cell hyperplasia, and occlusion of pulmonary veins (20,37). MCT-induced interstitial pulmonary fibrosis has also been described in mice (with variable doses and time points) (20,29). Electron micrographs of MCT-treated animals revealed degeneration of both lung endothelial and type I epithelial cells, as well as marked interstitial hypercellularity and fibrosis (43,44).…”