Exercise Does Not Attenuate Disease Progression in a Rat Model of Progressive Pulmonary Arterial Hypertensionстатья из журнала
Аннотация: PURPOSE: We previously demonstrated exercise training (ExT) could attenuate functional decline in a rat model of mild, stable pulmonary arterial hypertension (PAH) without worsening right ventricle (RV) maladaptive remodeling. The present work examines efficacy and safety of similar training in a rat model of more severe, progressive PAH. METHODS: Male SD rats (∼200g) received 60 mg/kg (s.q) of either monocrotaline (MCT) to induce PAH (PAH, n=14), or saline (CON, n=10). At 2 wks post-injection a 6-wk treadmill (TM) ExT program (60 min, 5x/wk) was initiated for a subset of PAH (PAH-ExT, n=7) and CON (CON-ExT, n=5). The balance in each group remained sedentary (PAH-SED n=7, and CON-SED n=5). VO2max was assessed pre-injection, and pre- and post-training via analysis of expired gases during incremental TM running. Individualized workloads for ExT were established relative to pre-training VO2max, at 50%VO2maxR). Other measures were performed following the 6 wk Ext/SED period. Values are mean±SE. RESULTS: Mortality plots were slightly worse for PAH-ExT (1 death at 34 days, 1 death at 40 days) vs PAH-SED (1 death at 40 days, 1 death at 58 days). Post-training VO2max was significantly lower (p<0.05) for the surviving PAH-ExT (33.6±4.8) vs PAH-SED (47.7±3.2, ml/kg/min). MCT-induced elevation in RV systolic pressure (RVSP; mmHg, normalized by mean BP) and RV hypertrophy (RVH; as RV/LV+septum) were higher (p<0.05) as expected in PAH but not different between PAH-ExT (RVSP =0.77±0.2, RVH=0.61±0.1) vs PAH-SED (RVSP =0.65±0.0, RVH=0.56±0.0). Echocardiographic parameters, while consistent with that expected for PAH vs CON, were also unaffected by ExT (p>0.05). Additionally, assay of caspase 3 activity indicated no difference (p>0.05) between PAH-ExT (0.023±0.007) vs PAH-SED (0.016±0.003) for RV apoptosis. However, trichrome+ staining was lower (p<0.05) in PAH-ExT (11.62±1.8) vs PAH-SED (23.23±4.3, % of area) indicating less myocardial fibrosis for the trained. As expected, RVSP, RVH, RV fibrosis, and RV apoptosis were normal in CON and not different between CON-ExT (0.27±0.0, 0.25±0.0, 5.28±0.9, and 0.013±0.007, respectively) vs CON-SED (0.31±0.0, 0.24±0.0, 9.86±1.5, and 0.010±0.007, respectively). CONCLUSION: For a rat model of severe, progressive PAH, functional decline is accelerated by mild intensity exercise training and is unexplained by effects on hemodynamic and RV parameters. Funding: American Heart Assoc. (Brown).
Год издания: 2015
Авторы: Mary Beth Brown, Tsungai J. Chingombe, Ronald M. Harper, Joshua Weyer, Brent Bremer, Sean J. Cooney, Amanda Fisher, Anthony Cucci, Robert G. Presson, Irina Petrache, Tim Lahm
Издательство: Lippincott Williams & Wilkins
Источник: Medicine & Science in Sports & Exercise
Ключевые слова: Pulmonary Hypertension Research and Treatments, Cardiovascular Effects of Exercise
Открытый доступ: closed
Том: 47
Выпуск: 5S
Страницы: 688–688