Induction of Right Ventricular Hypertrophy in Neonatal Guinea Pigs by Monocrotaline

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Abstract
The purpose of this study was to develop an experimental model of neonatal right ventricular hypertrophy which was similar to human congenital heart disease associated with pulmonary hypertension. Monocrotaline (200 mg/kg), a pyrrolizidine alkaloid, was injected into neonatal Hartley guinea pigs on the day of delivery. The occurrence of pulmonary hypertension and right ventricular hypertrophy was confirmed by pressure studies and a determination of the right ventricular wet weight and myocyte diameter on the seventh day after delivery. Right ventricular systolic pressure was significantly increased at 7 days after monocrotaline treatment compared with the untreated control group. The ratio of right ventricular systolic pressure to left ventricular systolic pressure, an indicator of pulmonary hypertension, was significantly elevated from 0.32 +/- 0.02 in the controls to 0.59 +/- 0.03 in the monocrotaline group. Right ventricular wet weight was also significantly increased, indicating right ventricular hypertrophy. The diameter of cardiac myocytes was significantly increased in the right ventricle, and was decreased in the left ventricle and interventricular septum in the monocrotaline group. Neonatal guinea pigs developed pulmonary hypertension and marked right ventricular hypertrophy within 1 week after treatment with monocrotaline. This simple experimental model may have features similar to those of human congenital heart disease associated with pulmonary hypertension.