Establishment of exercise induced pulmonary hypertension rat model induced by monocrotaline and early intervention effect of tadalafil

Abstract:

Objective：To establish exercise induced pulmonary hypertension（EiPH） rats model，diagnose in the early phase and treat as soon as possible，so as to assess the pulmonary hypertension（PH） progression，pulmonary artery remodeling and survival rate. Methods：Sixty male Sprague Dawely（SD） rats，with weight 200 to 220 g，were intraperitoneally injected with monocrotaline（MCT，60 mg/kg）. After injecting MCT，the mean pulmonary artery pressure（mPAP） under resting and exercising condition and maximum mPAP（mPAPmax） under exercising condition on the 1st，3rd，5th，7th and 9th day were measured. Rats with resting mPAP<25 mmHg and exercising mPAPmax>30 mmHg were classified into EiPH group；rats with resting mPAP≥25 mmHg were randomly divided into resting PH（rPH） group and PH group；rats with injection of saline were classified into control group. Rats in the EiPH and the rPH group were given same dose tadalafil（T） by gavage for two weeks. Echocardiography was performed at the end of experiment，right heart catheter was improved to measure the pulmonary artery pres－sure and the cardiopulmonary tissue was taken and kept. Results：On the 7th day after MCT injection，the exercising mPAPmax in the MCT group was higher than that in the control group[（38.5 ± 2.7） mmHg vs. （27.24 ± 0.46） mmHg，P=0.000]. On the 35th day after MCT injection，resting mPAP in the rPH+T group was increased[（26.67 ± 0.11） mmHg vs. （35.23 ± 0.47） mmHg，P=0.000]，right ventricular hypertrophy index was raised（0.34 ± 0.01 vs. 0.46 ± 0.02，P=0.004） and the percentage of pulmonary artery wall thickness（44.4% vs. 55.6%，P=0.008） was magnified. Conclusion：The EiPH rat model was successfully established. According to tadalafil intervention experiment，effectiveness of lowering blood pressure and inhibiting pulmonary vessel remodeling in the early phase is better than treating with a same dose drugs in the late phase.