LAUSR

Objectives: PAH induced by relatively high dose of monocrotaline (MCT) in animal is a subacute process, with a short survival period less than 1 month. The aim of this study was to establish an animal model of chronic PAH. Methods: 108 male Sprague-Dawley rats were randomly divided into three groups, including normal control, conventional, and novel. In conventional, a single dose of 40 mg/kg MCT was given intraperitoneally to induce PAH. Animals in the novel received twice intraperitoneal injection of 20 mg/kg MCT in a week. Mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling (the percentage of total wall thickness to external diameters of pulmonary arterioles diameter [WT%] and the percentage of wall area to the total area of vessels [WA%]) were assessed on the day 7, 14, 21 and 28 after first MCT administration. The numbers of survival rats were recorded till day 28. Results: 28 days after first MCT injection, mPAP (conventional 34.48 ± 2.36 mmHg, novel 31.58 ± 2.69 mmHg vs. control 17.30 ± 3.10 mmHg; P < 0.05), RVHI (conventional 53.68 ± 5.70%, novel 45.07 ± 11.21% vs. control 25.73 ± 6.04%), WA% (conventional 80.57 ± 3.92, novel 80.49 ± 7.63 vs. control 47.03 ± 6.95) and WT% (conventional 58.50 ± 3.27, novel 56.33 ± 6.87 vs. control 28.21 ± 3.94; P < 0.05) in conventional and novel were higher than control. Compared to conventional, mPAP and RVHI were lower in novel (P < 0.05). On the day 28 after first MCT injection, survival percentage in novel were higher than that in conventional (78.57 vs. 57.14%; P = 0.027; n = 22). Conclusion: Novel use of twice intraperitoneal injection of 20 mg/kg MCT could successfully induce chronic PAH and increase survival percentage compared with single injection of 40 mg/kg MCT in rats.