Acute Effects of Sildenafil on Ventricular Functions in Heart Failure Dogs Induced by Rapid Ventricular Pacing
Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
Heart failure (HF) is a rising clinical cardiovascular problem in geriatric small-breed dogs. Currently, effective medical therapy is not available to prevent cardiac remodeling. Sildenafil citrate is a selective phosphodiesterase-5 inhibitor that is widely used for treatment of pulmonary hypertension in dogs. Recent clinical studies of sildenafil in patients and rats with HF have reported improved cardiac functions. However, its effect in dogs with HF is not elucidated.
This study aimed to assess acute effects of sildenafil on LV functions by using echocardiography in heart failure dogs induced by rapid right ventricular pacing.
Four dogs implanted with right ventricular pacing led to induced HF by pacing at increasing rate (180-, 200-, 220-, 240-bpm/weeks). Once HF developed, the pacing rate was maintained at 180 bpm. Five weeks after increasing the rate of the pacemaker, physical examination, ECG, echocardiogram, blood pressure and NT-proBNP were obtained. Echocardiography, ECG and BP were performed at baseline (30 min after turning off pacemaker) and 1 h after sildenafil administration.
After 5 weeks of pacing, the EF and SF were 32.0 and 15.1%, respectively (p < 0.01). The NT-proBNP level was also significantly increased 56.0% from before pacing (p < 0.01). After oral sildenafil, the EF and SF were increased significantly (43.0% and 20.7%, respectively; p < 0.05). The diastolic functions (E/A ratio and IVRT) were also improved significantly, as suggested by shortened IVRT 20.2% and reduced E/A ratio 3.5% (p < 0.05).
This data suggested that acute oral sildenafil improved systolic and diastolic dysfunction in HF dogs.