Abstract 16202: Early Intervention in a Novel Early-Phase Pulmonary Hypertension Animal Model, Exercise-Induced Pulmonary Arterial Hypertension in Rat.

Introduction: The patients with pulmonary arterial hypertension (PAH) are commonly diagnosed at late stage with right heart failure, results in poor prognosis. Invasive cardiopulmonary exercise test is utilized to diagnose pulmonary vascular dysfunction in early stage, according to increased mean pulmonary arterial pressure (mPAP), but the pathologic changes of pulmonary artery and the effects of early intervention are unknown. Methods: Male Sprague-Dawley rats were administrated with monocrotaline (MCT, 60mg/kg) or vehicle by intraperitoneal injection. MPAP was measured via right heart catheter at rest and exercise on a treadmill every other day after MCT injection. Rats were divided into exercise-induced PAH group (EiPAH, mPAP < 25 mmHg at rest and > 30 mmHg at peak exercise), rest PAH group (rPAH, mPAP >25 mmHg at rest), treated with Tadanafil 9mg/kg by gavage for 14 days when diagnosed by RHC, respectively.Lung tissue was stained with Hematoxylin-Eosin, medial wall index of pulmonary artery was analyzed by Image-Pro. Results: The elevated peak mPAP during exercise test was presented at the day 7 (38.5 ± 2.7 mmHg versus vehicle 27.24 ± 0.46 mmHg, P <0.0001, Figure 1.a), rPAH was determined at the day 21 after MCT injection (34.7 ± 1.2 mmHg). Decreased mPAP was observed in the EiPAH group compared with the rPAH group (26.67 ± 0.11 mmHg versus 35.23 ± 0.47 mmHg, P <0.0001, Figure 1.b) after 14 days treatment with Tadanafil. Medial wall index of small pulmonary artery was 44.4% in EiPAH group and 61.2% in rPAH group (P =0.0003, Figure 1.c, pathology image Figure 2. a,b,c,d). Survival rate did not differ (P =0.427, Figure 1.d). Conclusion: This present study validates an exercise-induced rat model of pulmonary hypertension, early diagnosis and intervention decreases the mPAP and relieves the pulmonary vascular remodeling, which may offer a new avenue for testing potential mechanisms and clearing an early diagnosis and intervention for pulmonary hypertension. [ABSTRACT FROM AUTHOR]