TREATMENT

Treating canine pulmonary hypertension should be approached with several goals in mind. First and foremost, treatment should be aimed at decreasing clinical signs: improving exercise intolerance, dyspnea, and cough and decreasing syncopal events. In addition, treatment should also be instituted to decrease the patient's hospitalization time, improve quality of life, and increase survival time. These goals can be accomplished by identifying and treating the underlying cause of pulmonary hypertension and, often, by using medications to help decrease pulmonary arterial pressure and the workload of the right ventricle.

Based on recommendations from our human counterparts, therapy should be started in any patients with functional class III or IV disease, with the goal of reassigning them to class I or II.²⁰

Prostacyclin is a known vasodilator and platelet inhibitor and also has antiproliferative effects.^8,13 Prostacyclin analogues include epoprostenol, treprostinil, and iloprost. Epoprostenol and treprostinil are given intravenously. Treprostinil can be given subcutaneously, and iloprost is given as an inhalant. In people, these medications improve symptoms and survival. Side effects include anemia, thrombocytopenia, hypotension, and gastrointestinal symptoms.⁸

Prostacyclin analogues have been found to be experimentally effective in treating canine pulmonary hypertension, but there are no published clinical trials. Prostacyclin analogues improve cardiac output, vasodilation, and right ventricular performance.^21,22 Unfortunately, prostacyclin analogues are exorbitantly expensive and are not practical for administration in veterinary patients.

Endothelin antagonists

As discussed previously in Part 1 of this article series, endothelin-1 causes vasoconstriction, smooth muscle proliferation, and vascular remodeling. By antagonizing the actions of endothelin-1, pulmonary arterial pressure can be decreased. The most common endothelin antagonists include bosentan, sitaxsentan, and ambrisentan. These oral medications have been shown to improve exercise intolerance, pulmonary arterial pressure, and even pulmonary vascular resistance in people.^8,23 Side effects in people include dose-dependent hepatotoxicosis, anemia, and birth defects.⁸

Bosentan has been assessed in dogs in experimental settings. In these patients, bosentan was effective and was been found to decrease vascular remodeling in induced pulmonary hypertension, improve myocardial function, and decrease ventricular remodeling.^24,25 Unfortunately, there are no clinical trials of endothelin antagonists in dogs with naturally occurring disease. Endothelin antagonists, while less expensive than prostacyclin analogues, are considered cost-prohibitive in veterinary patients.

Nitric oxide and nitrates

Nitric oxide is an inhaled vasodilator, while isosorbide dinitrate and isosorbide mononitrate are oral vasodilators. Nitrates are given to people for their antianginal effects but have limited application for treating pulmonary hypertension. These medications are not commonly used in veterinary medicine because of potentially severe side effects.

L-arginine, the precursor to nitric oxide, has been administered to people with pulmonary hypertension. This drug is given orally and may improve nitric oxide concentrations and cause vasodilation. In people, this drug is questionably effective, but there are no studies in dogs.²⁶