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Simple Summary: Pulmonary hypertension is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol, a prostacyclin analog, is an intravenous pulmonary vasodilator used for treating pulmonary hypertension in humans; however, it has not been used in veterinary medicine. This study aimed to investigate the effects of epoprostenol on cardiac function and hemodynamics in canine models of chronic pulmonary hypertension. Six laboratory-owned dogs with chronic embolic pulmonary hypertension were anesthetized and underwent right heart catheterization and echocardiography before and after administering epoprostenol, dobutamine, dopamine, and pimobendan. In this study, high doses of epoprostenol significantly decreased pulmonary and systemic vascular resistance and increased left and right ventricular function. In contrast, dobutamine and dopamine significantly increased pulmonary arterial pressure and left and right ventricular function. Pimobendan significantly increased left and right ventricular function without increasing pulmonary arterial pressure. Our results indicate that high doses of epoprostenol might help effectively treat canine pulmonary hypertension through pulmonic and systemic vasodilating effects. Catecholamines improve left and right ventricular function; however, they might worsen the pathophysiology of pulmonary hypertension. Pimobendan also improved left and right ventricular function without worsening pulmonary hypertension pathophysiology; however, a stronger vasodilating effect was observed with epoprostenol. Pulmonary hypertension (PH) is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol is an intravenous pulmonary vasodilator used to treat PH in humans; however, its efficacy in dogs remains unknown. We investigated the cardiovascular effects of epoprostenol and several cardiac agents for acute heart failure in canine models of chronic PH. Six dogs with chronic PH were anesthetized and underwent right heart catheterization and echocardiography before and after infusion of epoprostenol, dobutamine, dopamine and pimobendane. (The drug administration order was the same for all dogs). High-dose epoprostenol (15–20 ng/kg/min) tended to decrease pulmonary arterial pressure (PAP) while significantly decreasing pulmonary and systemic vascular resistance and increasing left and right ventricular (LV and RV, respectively) function. Pimobendan significantly increased LV and RV functions without increasing PAP. Conversely, dobutamine and dopamine significantly increased LV and RV function as well as PAP. This study revealed the efficacy of epoprostenol in treating canine PH through its pulmonary and systemic vasodilating effects. Although catecholamines improve LV and RV function, they might worsen PH pathophysiology, and careful monitoring may be necessary when using these drugs. Pimobendan improved LV and RV function without increasing PAP; however, a stronger vasodilating effect was observed with epoprostenol. [ABSTRACT FROM AUTHOR]