The effect of sildenafil on pulmonary haemodynamics in a canine model of chronic embolic pulmonary hypertension

• Published in: Research in veterinary science 2020-12, Vol.133, p.106-110
• Main Authors: Akabane, Ryota, Sakatani, Atsushi, Ogawa, Mizuki, Nagakawa, Masayoshi, Miyakawa, Hirosumi, Miyagawa, Yuichi, Takemura, Naoyuki
• Format: Article
• Language: English
• Subjects: Administration, Oral; Anesthesia; Animals; Blood pressure; Carbon monoxide; Cardiac output; Cardiovascular disease; Catheters; Dog; Dog Diseases - drug therapy; Dogs; Dose-Response Relationship, Drug; Drug dosages; Female; Heart; Hemodynamics; Hemodynamics - drug effects; Hypertension; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - veterinary; Hypoxia; Laboratory animals; Lung - drug effects; Lung - physiopathology; Medical instruments; Microspheres; Oral administration; Pulmonary arteries; Pulmonary artery; Pulmonary hypertension; Right heart catheterisation; Sildenafil; Sildenafil Citrate - therapeutic use; Statistical analysis; Vascular Resistance - drug effects; Vasodilator Agents - therapeutic use; Veins & arteries; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2020.08.019

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. •The effects of different doses of oral sildenafil in a canine model of pulmonary hypertension (PH) were evaluated.•A PH model was created by repeatedly injecting microspheres into the pulmonary arteries.•1, 2 and 4 mg/kg of oral sildenafil in a canine model of PH decreased pulmonary artery pressure in a dose-dependent manner.•Sildenafil decreased pulmonary vascular resistance without notable changes in systemic vascular resistance.