Pulmonary hypertension and ECG changes from monocrotaline pyrrole in the rat

Abstract

Chemically synthesized monocrotaline pyrrole (MCTP) was administered to adult male rats at a dose of 5 mg/kg in the tail vein. Controls received an equivalent volume of dimethylformamide vehicle. Rats were killed at 3, 5, 7, 10, and 14 days after treatment. Bronchopulmonary lavage fluid lactate dehydrogenase activity and lung weight were significantly elevated at 4 and 7 days, respectively, after MCTP, indicating that pulmonary damage had occurred. White blood cell count was elevated 7 days after treatment. Mean pulmonary arterial pressure was also first elevated in treated (22 +/- 3 mmHg) compared with control (16 +/- 1 mmHg) animals 7 days after treatment. Right ventricle-to-left ventricle plus septum weight ratios were significantly increased in treated (0.429 +/- 0.015) vs. control (0.320 +/- 0.015) animals 14 days after treatment. Development of right heart enlargement correlated with a shift in the QRS complex mean electrical axis in the frontal plane of the electrocardiogram. These results indicate that MCTP produces effects similar to that caused by monocrotaline, that pulmonary arterial pressure increases from control levels between 5 and 7 days after treatment, and that measurement of mean electrical axis of the electrocardiogram may be a useful, noninvasive method to monitor MCTP-induced cardiac changes in vivo.