Browsing by Subject "skeletal muscle dysfunction"

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    EFFECT OF TREADMILL RUNNING ON CARDIAC AND SKELETAL MUSCLE METABOLISM AND RIGHT VENTRICLE INFLAMMATION IN RATS WITH PULMONARY ARTERIAL HYPERTENSION
    (Office of the Vice Chancellor for Research, 2012-04-13) Chingombe, Tsungai J.; Lahm, Tim; Reddy, Jag; Fisher, Amanda; Petrache, Irina; Brown, Mary Beth
    It has been suggested that a shift from oxidative to non-oxidative (glycolytic) metabolism promotes a right ventricle (RV) and skeletal muscle dysfunction in patients with pulmonary arterial hypertension (PAH), contributing to their reduced exercise tolerance. Exercise training may ameliorate this glycolytic switch in PAH as it does for other cardiopulmonary diseases. However, whether exercise-induced cardiac stress also promotes detrimental RV inflammation in PAH has not yet been thoroughly examined. We hypothesized that exercise training will promote a shift back towards the more efficient oxidative metabolism in cardiac and skeletal muscle of PAH rats and that 45 minutes of exercise at a prescribed moderate intensity will not promote greater RV inflammation in PAH rats. Tissues were obtained from monocrotaline-induced PAH and healthy control rats immediately following a 45 min treadmill run (75% VO2max) that concluded a 4 week treadmill familiarization/running program (15-45 min, 4x/wk). A group of unexercised PAH and healthy rats served as sedentary controls. Immunofluorescent staining (IF) for inflammatory markers CD45 (lymphocytes) and CD68 (macrophages) in cryofixed RV sections were used to assess the acute inflammatory response to exercise. In fixed soleus and RV sections, IF for the glucose transporter Glut1, and for capillary marker CD31, were used as indicators of glycolytic metabolism and tissue capillarization, respectively. Data thus far indicates no greater acute exercise-induced RV inflammation in PAH rats compared to healthy rats. We observed higher expression of Glut1 and lower capillarization in the RV and soleus of PAH rats, indicative of a shift toward greater dependency on non-oxidative metabolism. However, since Glut1 levels for exercised rats were measured in tissue harvested immediately following a run bout, evaluation of a chronic training effect on Glut1 expression is potentially confounded by the acute exercise effect and therefore remains to be investigated in a follow-up study.
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    Exercise Training Improves Cardiac and Skeletal Muscle Metabolism in Rats with Pulmonary Arterial Hypertension
    (Office of the Vice Chancellor for Research, 2013-04-05) Gaidoo, Richard G.; Crist, Jacob; Little, Nathaniel; Chingombe, Tsungai J.; Fisher, Amanda; Presson, Robert G.; Lahm, Tim; Petrache, Irina; Brown, Mary Beth
    In patients with pulmonary arterial hypertension (PAH), a shift from oxidative to glycolytic metabolism promotes right ventricular (RV) and skeletal muscle dysfunction that contributes to reduced exercise tolerance. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this glycolytic switch in PAH and improve exercise capacity. The purpose of this research is to investigate ExT in a rat model of PAH on markers of glycolytic and oxidative metabolism in RV and skeletal muscle. Male Sprague-Dawley rats received monocrotaline (MCT, 40 mg/kg, s.q.) to induce PAH (n= 13), or saline, for healthy controls (n=5). After 2 wks, with MCT-induced PAH established, 6 wks of treadmill (TM) ExT was initiated for a subset of PAH animals (PAH-ExT, n= 6) and healthy controls (CON-ExT, n=3). ExT runs progressed up to 60 min at mild relative intensity, 50% of maximal aerobic capacity (VO2max). VO2max was assessed at baseline, in pre-training and post-training TM testing via analysis of expired gases. Abundance of Glut-1, a marker of glycolytic metabolism, was evaluated in cryosections of RV and soleus with immunofluorescent (IF) staining and quantification. Data are presented as mean±SE. MCT-ExT rats maintained aerobic capacity over 6 wks better than sedentary counterparts (MCT-SED)(VO2max= -134±109 vs. -521±129 ml/kg/hr, p=0.04) and was not different than CON-ExT (-201±31 ml/kg/hr, p=0.82). A lower abundance of Glut-1 was observed in both RV and soleus myocytes of PAH-ExT rats (MPI= 10.9 ±0.9 for RV; 13.7±0.8 for soleus) compared to PAH-SED rats (15.7±2.4, p=0.05, for RV; 17.4±1.4, p=0.04, for soleus) and was similar to CON-ExT rats (13.0±2.2, p=0.33, for RV; 9.0±2.3, p=0.26, for soleus), indicative of a shift toward greater dependency on oxidative metabolism. Exercise training attenuates functional decline following MCT administration in rats. Preservation of aerobic capacity may be explained by promotion of more efficient RV and skeletal muscle mitochondrial substrate utilization.