Retrospective Evaluation of Sildenafil Citrate as a Therapy for Pulmonary Hypertension in Dogs

Abstract

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPs) > or = 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPs, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPs was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPs was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPs and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

“…It has been reported in multiple studies that not only is the magnitude of response to PDE5A inhibitors, such as sildenafil citrate, weak and often unsuccessful in the treatment of canine PH, but it also is apparently variable on an individual dog basis 15, 16, 17. With the exception of few pharmacogenomics discovery reports, the concept of individualized medicine is quite new for veterinary health care, but may elucidate the physiologic mechanism for these observations 2, 3, 4.…”

“…Although it occurs secondary to multiple inciting causes and several classification schemes have been described, the overall prognosis and response to therapy are poor in dogs with the severe form of the disease 15. In one study, median survival time was only 91 days 16. In many cases of severe PH, dogs are euthanized because of failure to respond to therapy and progressive respiratory distress 15, 16, 17.…”

“…In many cases of severe PH, dogs are euthanized because of failure to respond to therapy and progressive respiratory distress 15, 16, 17. Phosphodiesterase type V inhibitors (PDE5‐I) are commonly prescribed for PH because they increase pulmonary vascular concentrations of cGMP, which in turn promote endogenous nitric oxide concentrations and resultant vasodilatation 15, 16, 17…”

A Case of Long-Term Sildenafil Therapy in a Young Dog with Pulmonary Hypertension

“…The selective phosphodiesterase type 5 (PDE5) inhibitor sildenafil citrate is a potent pulmonary vasodilator that causes the concentration of cyclic guanosine monophosphate to increase, which subsequently result in nitric oxidemediated vasodilation [2,4,11,12,17]. Sildenafil decreases pulmonary artery pressure and pulmonary vascular resistance, and increases cardiac output without decreasing systemic blood pressure or increasing wedge pressure in humans [9].…”

“…Sildenafil decreases pulmonary artery pressure and pulmonary vascular resistance, and increases cardiac output without decreasing systemic blood pressure or increasing wedge pressure in humans [9]. Additionally, sildenafil might also affect vascular remodeling [2]. Sildenafil has been used to successfully treat pulmonary artery hypertension (PH) in both children and adults [1,4,8,15].…”