Abstract 17790: Death in Experimental Pulmonary Hypertension Induced by Monocrotaline: It's Not From Pressure Overload
Background: The most frequently used animal model of pulmonary hypertension is the rat injected with the alkaloid phytotoxin monocrotaline (MCT). The high mortalitity rate in this model is usually attributed to pressure overload induced right ventricular (RV) failure. We hypothesize, however, that pressure overload is not responsible for the death of MCT rats.
Methods: Pulmonary vascular remodeling was induced in 6 week old male Sprague-Dawley rats by MCT, or by exposing them to the VEGF-R blocker SU5416 and hypoxia (SuHx).
Results: Mortality rates in MCT-exposed rats were 25% at 4 weeks and 75% at 5 weeks, whereas there were no deaths observed in SuHx rats within the first three months after SU5416/hypoxia exposure. At the 5 week time-point, there was a higher degree of pressure overload in the SuHx model (see figure), whereas echocardiographically determined parameters of RV function were not different. Left ventricular dysfunction was frequently seen by echocardiography in MCT rats, but not in SuHx rats. RV fibrosis and capillary rarefaction were more severe in the SuHx model.
Conclusions: Despite a relatively mild degree of pressure overload, RV dysfunction and RV remodeling, there is a high mortality after MCT injection. This data suggests that death in MCT rats is unrelated to pressure-overload induced RV failure. Biventricular failure, hypoxemia and veno-occlusive disease of the liver could be alternative explanations for the high mortality rates of MCT rats.
- © 2010 by American Heart Association, Inc.