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Effect of Treadmill Running on Cardiac and Skeletal Muscle Metabolism and Right Ventricular Inflammation in Rats with Monocrotaline-induced Pulmonary Arterial Hypertension (PAH)

Mary Beth Brown

J Reddy

Tsungai Chingombe

A. J. Fisher

Robert Presson

Tim Lahm

I Petrache


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Conference: 2012 International PHA Conference and Scientific Sessions

Release Date: 06.22.2012

Presentation Type: Abstracts

BACKGROUND: A shift from oxidative to non-oxidative (glycolytic) metabolism promotes right ventricular (RV) and skeletal muscle dysfunction in patients with PAH, thereby contributing to reduced exercise tolerance. As seen in other cardiopulmonary diseases, exercise training may also ameliorate this glycolytic switch in PAH. However, if too vigorous, exercise-induced cardiac stress in PAH may also promote detrimental RV inflammation. The purpose of this study was to evaluate the effect of chronic treadmill exercise followed by 45 minutes of acute exercise at a prescribed moderate intensity on RV and skeletal muscle glycolytic metabolism in rats with stable PAH. Further, we hypothesized that 45 minutes of acute exercise at a prescribed moderate intensity will not promote greater RV inflammation in PAH rats.

METHODS: RV systolic pressure (RVSP; via Millar catheter) and RV hypertrophy (RVH; expressed as RV/LV+septum) were measured. Tissues were obtained from rats with monocrotaline (MCT)-induced PAH (40 mg/kg i.p.) and healthy control rats immediately following a 45 min treadmill run (standardized at 75% VO2max) that concluded a 4 week treadmill familiarization/ progressive running program (15-45 min, 4x/wk). A group of unexercised PAH and healthy rats served as sedentary controls. Immunofluorescent staining (IF) for inflammatory marker CD45 in cryofixed RV sections was used to evaluate 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.

RESULTS: MCT administration resulted in a moderate elevation in RVSP (mean±SE 36.7±2.3 vs 29±0.6 mmHg) and RVH (0.37±0.02 vs 0.24±0.01). Interestingly, we observed higher expression of Glut1 and lower capillarization in both RV and soleus of PAH rats, indicative of a shift toward greater dependency on non-oxidative metabolism. Importantly, no greater acute exercise-induced RV inflammation was observed in PAH rats compared to healthy rats. RV and soleus capillarization, but not Glut1 expression, was greater in exercised vs. sedentary PAH rats.

CONCLUSION: Chronic exercise increases RV and soleus capillarization. A single exercise bout at 75% VO2max does not increase RV inflammation in rats with moderate PAH. 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 may potentially be confounded by the acute exercise effect. The effect of chronic exercise training (without an acute bout) on RV and soleus inflammation and metabolism is currently under investigation.

FUNDING: T-32 HL091816