Efficacy of Exercise and Testosterone to Mitigate Atrophic Cardiovascular Remodeling

Purpose Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. This randomized controlled trial was designed 1) to characterize the time course of unloading-induced morphofunctional remodeling and 2) to examine the effects of exercise with and without low-dose testosterone supplementation on cardiac biomarker, structural, and functional parameters during unloading. Methods Twenty-six subjects completed 70 d of head-down tilt bed rest (BR): 9 were randomized to exercise training (Ex), 8 to EX and low-dose testosterone (ExT), and 9 remained sedentary (CONT). Exercise consisted of high-intensity, continuous, and resistance exercise. Cardiac morphology (left ventricular mass [LVM]) and mechanics (longitudinal, radial, and circumferential strain and twist), cardiovascular biomarkers, and cardiorespiratory fitness (VO_2peak) were assessed before, during, and after BR. Results Sedentary BR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain in CONT, whereas Ex and ExT mitigated decreases in LVM and function. Twist was increased throughout BR in sedentary BR, whereas after an initial increase at BR7, there were no further changes in twist in Ex and ExT. HDL cholesterol was significantly decreased in all groups compared with pre-BR (P < 0.007). There were no significant changes in other cardiovascular biomarkers. Change in twist was significantly related to change in VO_2max (R = 0.68, P < 0.01). Conclusion An integrated approach with evaluation of cardiac morphology, mechanics, VO_2peak, and biomarkers provides extensive phenotyping of cardiovascular atrophic remodeling. Exercise training and exercise training with low-dose testosterone supplementation abrogates atrophic remodeling.