AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
High-Intensity Exercise Fails to Improve Right Ventricular Biomechanics in Severe Experimental Pulmonary Hypertension
By Cobb T, Kumar M, Abdel-Hafiz M et al.
Introduction: Pulmonary Hypertension (PH) is a rare disease in which elevated pulmonary pressure leads to right ventricle (RV) failure and death. Previous studies showed that high intensity interval training (HIIT) exercise in a rat model of mild monocrotaline PH improved RV function and decreased fibrosis. We hypothesize that HIIT exercise in animals during development of severe experimental PH would prevent development of RV fibrosis in a sexually dimorphic manner, resulting in decreased RV stiffness. Methods: After treadmill acclimatization, rats were randomized to undergo HIIT or remain sedentary. PH was induced through injection of Sugen (SU5416, inhibitor of vascular endothelial growth factor (VEGF)) followed by whole body hypoxia for 3 weeks, with additional 3 weeks of normoxia (SuHx). The exercise protocol consisted of a two-minute warm-up followed by five-minute cycles of HIIT four days a week for 5 weeks. Critical speed testing for endurance was conducted prior to the first week and during the 6 th week of the study. A HIIT cycle was defined as two minutes at 85% of CST, followed by three minutes at 50% of CST. After 6 weeks, rats underwent invasive hemodynamics under anesthesia. The RV was harvested, embedded in OCT, and sliced at 5-micron thickness and placed on glass slides. Slides were stained for collagen with picrosirius red, and the percent collagen was calculated using a propriety code in MatLab. Atomic Force Microscopy (AFM) was performed to assess tissue stiffness. Results: SuHx animals developed severe PH. HIIT did not alter PH severity, RV contractility, or RV-pulmonary artery coupling but resulted in a reduced cardiac index in females only. AFM analysis revealed no significant differences in RV stiffness among control, SuHx, and SuHx+HIIT groups. However, both male and female animals undergoing HIIT without PH induction exhibited significant changes in RV stiffness. The average RV stiffness of both males and females reduced 54.2% and 52.5% respectively. Collagen analysis showed a trend toward increased fibrosis in male SuHx animals, with a significant difference between males and female SuHx sedentary animals. SuHx sedentary males had an average collagen percentage of 8.96%,while females had an average of 3.07%. These values were reduced with HIIT, though this did not reach statistical significance. Conclusion: HIIT did not reduce RV fibrosis or stiffness in male or female animals with SuHX-PH but worsened cardiac index in females only. These findings suggest that in this model of severe PH, the RV is vulnerable to decompensation, and additional hemodynamic stress from high-intensity exercise may exacerbate dysfunction rather than conferring benefit. A future direction will include an analysis of left ventricular biomechanics, along with an analysis of estrogen receptor alpha and mutant rats.