Structured Exercise Regimen in Pulmonary Hypertension-Right Ventricular Failure in an Ovine Model

Right heart failure (RHF) is a significant cause of morbidity and mortality from pulmonary hypertension (PH). To better understand the pathophysiology and implications of exercise-induced stress, we implemented an exercise regimen to further characterize this disease using our previously developed ovine model of chronic pulmonary hypertension-right ventricular failure (PH-RVF). To this end, eight Dorset cross sheep underwent the PH-RVF model via ligation of the left pulmonary artery (LPA) and progressive occlusion of the main pulmonary artery (MPA) with an inflatable cuff. The cuff and right ventricle (RV) pressure lines were subcutaneously tunneled to a port for access. Over eight weeks, each sheep underwent a weekly exercise regimen and cuff check (CC). The exercise regimen consisted of working speeds and recovery speeds for 10 min each. During exercise, we accessed both ports to transduce cuff pressure, hemodynamics, and take RV blood gases. At exercise conclusion, the PA cuff was inflated by 150-200 mmHg to increase RV afterload. A CC and RV blood gas were performed a few days after inflation to confirm cuff pressure and ensure compensation. Over the course of eight weeks, the SvO2 remained relatively stable at maximum intensity at week 1 vs week 8: 62.7 ± 4.5% vs 69.8 ± 4.0% despite the RVSP increasing from week 1 to week 8: 78 ± 8 mmHg vs 96 ± 8 mmHg. Additionally, the distance traveled increased from week 1 to week 8: 1390 ± 297 m vs 1834 ± 189 m, despite the PA cuff pressure at week 8 being increased to 777 ± 98 mmHg. This suggests that despite increased RV afterload, exercise may aid in an adaptive response and compensation to exercise in the setting of PH-RVF. This exercise regimen provides novel information about the effects of exercise in PH-RVF and enables complex studies of exercise physiology in a large animal model of PH-RVF.