Effect of Exercise on Experimental Pulmonary Hypertension: A Focus on Right Ventricular Biomechanics

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Presenter Information(s)

Tristan Cobb

Abstract or Description

Introduction. Pulmonary Hypertension (PH) is a disease in which elevated pulmonary pressures lead to right ventricle (RV) failure and death. Previous preclinical studies showed that high intensity interval training (HIIT) in a rat model of mild monocrotaline PH improved RV function and decreased fibrosis. We hypothesize that implementing HIIT in rats with severe experimental PH would prevent development of RV fibrosis resulting in decreased RV stiffness.

Methods. Male and female adult rats were induced with Sugen hypoxia PH (SuHx) with injection of Sugen (SU5416, inhibitor of vascular endothelial growth factor (VEGF)) followed by whole body hypoxia for 3 weeks, plus 3 weeks of normoxia. Rats were randomized to undergo HIIT 4 days a week for 5 weeks or remain sedentary. After 6 weeks, rats underwent invasive RV and LV 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) to assess tissue stiffness.

Results. SuHx animals developed severe PH, however HIIT had no effect on severity of PH, contractility, or cardiac output, but resulted in decreased RV/PA coupling (the ratio of end-systolic elastance to arterial elastance). AFM analysis showed no statistically significant differences in RV stiffness across conditions. Collagen analysis showed a trend in increase of collagen/fibrosis within SuHx which decreased with HIIT, however this was not statistically significant.

Conclusion. HIIT does not significantly reduce RV fibrosis or stiffness in animals with SuHX-PH. This may be attributed to the severity of the PH in this model. A future direction will involve exercise experiments with healthy mice and rats to observe the effects of exercise on the RV without the presence of severe disease.

Mentor

Dr. Brisa Peña Castellanos