Morphological features in dynamics of monocrotaline-induced pulmonary arterial hypertension in vivo

Abstract

Objective. To investigate the dynamics of pathomorphological changes in lung and right ventricular tissues in rats following injections of 60 mg/kg monocrotaline for 8 weeks. Methods. The study was performed on white mongrel male rats treated with monocrotaline 60 mg/kg, s.c. Samples of lung and heart tissues were collected for morphological studies every two weeks following the monocrotaline treatment. Results. In the first four weeks of the experiment, initial signs of structural remodeling were observed in the lungs and myocardium. These signs were evident as medial hypertrophy of pulmonary arteries with preserved lumen and minor perivascular infiltrates; increased apoptosis of endothelial cells; and segmental injury of cardiomyocytes with right ventricular hypertrophy. Irreversible, progressive pathology was observed in studied tissues by the end of experiment, which included occlusion of the vascular lumen in pulmonary arteries due to intimal fibrosis and medial hypertrophy in the lung tissue affected by perivascular inflammation. Plexiform arteriopathy was established in some samples at 8 weeks. Right ventricular cardiomyocytes showed aseptic necrosis with transformation into reactive fibrosis and right heart dilatation. Conclusion. This in vivo study established the time windows for reversibility of morphological alterations in lung and myocardial tissues characteristic of pulmonary arterial hypertension.