The effects of different doses of orally administered sildenafil on pulmonary haemodynamics in dogs with pulmonary hypertension (PH) have not been documented in an invasive and quantitative manner. In this study, we examined the effects of oral sildenafil using a canine model of chronic embolic PH (CEPH). This CEPH model was created by repeatedly injecting microspheres through a catheter into the pulmonary artery under general anaesthesia at regular weekly intervals over several months. The CEPH dogs received 1, 2 or 4 mg/kg of sildenafil orally twice a day for seven days. Then, haemodynamic measurements including pulmonary artery pressure (PAP), systemic artery pressure (SAP), pulmonary artery wedge pressure (PAWP), right atrial pressure (RAP) and cardiac output (CO) were obtained after seven days of sildenafil administration via right heart catheterisation and oscillometric blood pressure measurements.

Sildenafil was well tolerated in this study. Sildenafil administered at doses of 2 and 4 mg/kg significantly decreased systolic PAP compared with before administration. In addition, all doses of sildenafil significantly decreased the mean and diastolic PAP. Furthermore, 4 mg/kg of sildenafil significantly decreased PAP compared with 1 mg/kg. Sildenafil also significantly decreased pulmonary vascular resistance without notable changes in SAP or systemic vascular resistance. The PAWP, RAP and CO did not increase significantly at any doses. In conclusion, the oral administration of sildenafil to CEPH models decreased PAP in a dose-dependent manner.

尚未以侵袭性和定量的方式证明不同剂量的口服西地那非对肺动脉高压狗的肺血流动力学的影响。在这项研究中，我们使用慢性栓塞性PH（CEPH）犬模型检查了口服西地那非的作用。此CEPH模型是通过在全身麻醉下于几个月内每周定期将微球通过导管反复注射到肺动脉中而创建的。CEPH犬每天两次口服1、2或4 mg / kg西地那非，连续7天。然后，进行血液动力学测量，包括肺动脉压（PAP），全身动脉压（SAP），肺动脉楔压（PAWP），

西地那非在这项研究中耐受良好。与给药前相比，西地那非以2和4 mg / kg的剂量给药可显着降低收缩期PAP。另外，所有剂量的西地那非均显着降低了平均PAP和舒张PAP。此外，与1 mg / kg相比，西地那非4 mg / kg显着降低了PAP。西地那非还可以显着降低肺血管阻力，而SAP或全身血管阻力无明显变化。在任何剂量下，PAWP，RAP和CO均未显着增加。总之，西地那非对CEPH模型的口服给药以剂量依赖的方式降低了PAP。