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Pneumotoxicity and thrombocytopenia after single injection of monocrotaline
Abstract:
Adult Sprague-Dawley rats were treated once with 105 mg/kg monocrotaline (MCT) subcutaneously 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, whereas a lower dose (60 mg/kg) did not result in right ventricular hypertrophy 2 wk after treatment. The treatment regimen described has advantages over administration of MCT by ingestion and may prove suitable for investigations of the mechanism by which MCT results in pulmonary hypertension.
Insights
Monocrotaline (MCT) injection in rats causes early platelet count decrease and later pulmonary vascular endothelial dysfunction. These changes precede right heart hypertrophy, indicating a progressive model for pulmonary hypertension research.
Area of Science:
- Pulmonary Hypertension Research
- Toxicology
- Cardiovascular Physiology
Background:
- Monocrotaline (MCT) is a known toxin that can induce pulmonary hypertension.
- Understanding the temporal progression of MCT-induced pulmonary hypertension is crucial for developing effective treatments.
Purpose of the Study:
- To characterize the early and late effects of a single subcutaneous dose of MCT on rat pulmonary vasculature and cardiac function.
- To establish a reliable animal model for studying the mechanisms of MCT-induced pulmonary hypertension.
Main Methods:
- Adult Sprague-Dawley rats received a single subcutaneous injection of MCT (105 mg/kg) or saline.
- Animals were assessed at 2, 5, 10, and 14 days post-injection.
- Measurements included platelet count, 5-hydroxytryptamine clearance, pulmonary inflow perfusion pressure, and right heart hypertrophy.
Main Results:
- MCT treatment led to a decrease in platelet count by days 2-10.
- Pulmonary vascular endothelial function, assessed by 5-hydroxytryptamine clearance, decreased progressively from day 5 onwards.
- Elevated inflow perfusion pressure and right heart hypertrophy were observed by day 14.
- Dose-dependency was noted, with higher MCT doses causing mortality and lower doses not inducing hypertrophy within 2 weeks.
Conclusions:
- Subcutaneous MCT administration provides a time-dependent model for pulmonary hypertension.
- Early indicators include platelet count changes and endothelial dysfunction, followed by hemodynamic alterations and cardiac remodeling.
- This model offers advantages for investigating the mechanisms underlying MCT-induced pulmonary hypertension.