Pneumotoxicity and thrombocytopenia after single injection of monocrotaline

Abstract

Adult Sprague-Dawley rats were treated once with 105 mg/kg monocrotaline (MCT) s.c. or an equivalent volume of isotonic saline and examined 2, 5, 10 and 14 days later. The earliest changes observed were in the platelet count, which was decreased in the MCT animals at 2, 5 and 10 days postinjection. Clearance of perfused 5-hydroxytryptamine, a function of pulmonary vascular endothelium, was unaltered in isolated lungs of treated rats until 5 days after dosing, but decreased progressively thereafter in the MCT animals and was 24% less than controls by 14 days. The magnitude of this effect was dose related. Inflow perfusion pressure was elevated in perfused lungs of MCT-treated animals at day 14. Right heart hypertrophy, measured as an increase in the ratio of right ventricle to left ventricle plus septum weights, was not evident until 14 days after treatment. A larger dose of MCT (130 mg/kg) resulted in significant mortality; a lower dose (60 mg/kg) did not result in right ventricular hypertrophy 2 wk after treatment. The treatment regimen had advantage over administration of MCT by ingestion and may prove suitable for investigations of the mechanism by which MCT results in pulmonary hypertension.