Conference: 2014 International PHA Conference and Scientific Sessions
Release Date: 06.22.2014
Presentation Type: Abstracts
File Download: 2014 Conference Abstract - Mary Brown
Download Adobe Acrobat
: In pulmonary hypertension, a shift from oxidative to non-oxidative (glycolytic) metabolism promotes right ventricular (RV) and skeletal muscle (SkM) dysfunction that contributes to reduced exercise tolerance.
Background: In pulmonary hypertension, a shift from oxidative to non-oxidative (glycolytic) metabolism promotes right ventricular (RV) and skeletal muscle (SkM) dysfunction that contributes to reduced exercise tolerance. In a hypoxic pulmonary hypertension (HPH) rat model, we tested the hypothesis that exercise training (ExT) at moderate relative intensity will improve aerobic capacity by inhibiting the switch to glycolytic metabolism in RV and SkM without accelerating adverse RV remodeling.
Methods: A 6 wk treadmill (TM) running program (5 sessions/wk @ 75% of VO2max reserve) in normoxia was initiated for male Sprague-Dawley (180-200g) rats (ExT, n=9), progressed up to 60 min/session. Sedentary counterparts (SED, n=7) were placed on a stationary TM on a matched schedule. After 3 wks, housing for a subgroup of ExT (HPH-ExT, n=6) and SED (HPH-SED, n=4) rats was relocated to hypobaric hypoxia (Patm=362 mmHg; 10% FiO2) for the remaining 3 wks of the training program. VO2max was assessed at 3 timepoints via analysis of expired gases: pre-ExT, pre-hypoxia, and post-ExT. At the conclusion of the 6wk ExT program, echocardiographic parameters, RV systolic pressure (RVSP; via Millar catheter) and cardiac output (CO, flow probe) were measured, and tissues were harvested. Membrane glucose transporter Glut-1, a marker of glycolytic metabolism, was evaluated in RV and SkM (soleus) cryosections by immunofluorescence. Data are presented as mean±SE.
Results: HPH-ExT rats maintained aerobic capacity over the 6 wk period significantly better (p<0.05) vs. HPH-SED (ΔVO2max= 88±82 vs. -315±96 ml/kg/hr) and were similar (p>0.05) to normoxic ExT rats (ΔVO2max= 13±263 ml/kg/hr). Neither the higher RVSP, lower CO, nor RV hypertrophy induced by hypoxia (p<0.01) were significantly affected by ExT (p>0.05). Echocardiographic parameters were also unaffected by ExT (p>0.05). SkM hypertrophy was observed as expected with ExT (soleus wt/body wt = 0.45±0.0 in HPH-ExT vs. 0.38±0.0 in HPH-SED, p=0.03, but SkM Glut-1 expression was not different (p>0.05) between groups. A marked reduction in RV Glut-1 was observed in HPH-ExT (MPI= 16.9±1.7) vs. HPH-SED (25.7±1.7, p<0.01), and was similar (p>0.05) to that in normoxic ExT rats (14.0±1.2), indicative of greater RV dependency on oxidative metabolism.
Conclusions: Exercise training attenuates HPH-induced functional decline in rats without accelerating adverse RV hypertrophy. Improved aerobic capacity despite unaltered pulmonary hemodynamics may be explained, in part, by promotion of more efficient RV mitochondrial substrate utilization. Funding: Indiana University Research Support Funds Grant.
Type: Basic Science