Investigation of Beraprost Sodium on Cardiac Function and Hemodynamics in Canine Models of Chronic Pulmonary Hypertension

Abstract

Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by increased pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. No study has evaluated the utility of Beraprost sodium (BPS) in dogs with PH. This study aimed to evaluate the effect of BPS on cardiac function and hemodynamics and examine the optimal dose of BPS in canine models of chronic embolic PH. In this prospective crossover study, three doses of BPS (5, 15, and 25 μg/kg, twice a day) were examined in eight canine models of chronic embolic PH. All model dogs underwent invasive PAP measurement, echocardiography, and non-invasive systemic blood pressure measurement before and after continuous administration of oral BPS for 1 week. No side effects of BPS were observed in any dog during the study. All doses of BPS significantly decreased systolic PAP and pulmonary vascular impedance. Additionally, systemic vascular impedance significantly decreased with 15 and 25 μg/kg of BPS. The right ventricular stroke volume and longitudinal strain significantly decreased with all doses of BPS. The left ventricular stroke volume and circumferential strain decreased with 15 μg/kg BPS. BPS was well-tolerated in this study. A dose-dependent vasodilating effect on pulmonary vessels was observed in canine models of chronic PH. Additionally, 15 μg/kg BPS showed a balanced vasodilating effect on systemic and pulmonary vessels. Furthermore, with a decrease in systemic and pulmonary vascular impedance, the left and right ventricular functions were significantly improved. Our results suggest that BPS may be useful in the treatment of canine PH.

Keywords: dog; myocardial function; pulmonary vascular resistance; pulmonary vasodilator; right ventricular strain; speckle tracking echocardiography; systemic vascular resistance.

Figure 1

Changes in pulmonary and systemic vascular impedance by three doses of beraprost sodium administration (5, 15, and 25 μg/kg). Values are the means ± standard deviations.

Figure 2

Representative data of two-dimensional speckle tracking echocardiography-derived myocardial strain before and after 15 μg/kg beraprost sodium (BPS) administration: left ventricular longitudinal strain [LV-SL (A)], left ventricular circumferential strain [LV-SC (B)], right ventricular longitudinal strain obtained from only right ventricular free wall analysis and right ventricular global analysis [RV-SL_3seg (C) and RV-SL_6seg (D), respectively]. For each variable, the left figure represents the myocardial strain before BPS administration, and the right represents that after BPS administration.