Abstract 15989: Exercise Training Improves Aerobic Capacity and Right Ventricular Function in a Rat Model of Chronic Pulmonary Embolism

Abstract

Introduction: Right ventricular (RV) dysfunction worsens outcome after pulmonary embolism. This study investigated whether aerobic exercise training may induce salutary RV adaptations to improve RV contractility and exercise capacity in a rat model of chronic PE (CPE). Methods: Male Sprague-Dawley rats (350-400g) received a single dose of polystyrene microspheres (221.000/100g, 85 μm, jugular vein) and SU 5416 (20mg/kg, s.c.) to produce CPE with pulmonary hypertension (CPE, n=6), or vehicle (Sham, n=4). A subgroup of Sham and CPE (Sham+EXE and CPE+EXE, n=4-6) underwent 6 weeks of treadmill training at mild relative intensity (50% of VO 2 max), 60 min, 5x/wk. Sedentary counterparts were placed on a stationary treadmill (Sham+SED and CPE+SED, n=4-6). VO 2 max was assessed via analysis of expired gases at three time points: pre-CPE, 3 days and 6 weeks after CPE induction. Echocardiography and in-vivo RV cannulation were performed during the 6 th week. Hearts were extirpated and perfused via the aorta using Langendorff’s technique. Results: CPE+SED had lower (p<0.05) VO 2 max (in ml/kg/hr) at 3 days (2491±250), and 6 weeks (2791±121) post-CPE, vs. Sham+SED (3 days: 3407±151; 6 weeks: 3876±68). Exercise training attenuated CPE-induced decrement in VO 2 max (CPE+EXE, 3087±93 ml/kg/hr, p<0.05 vs. CPE+SED). Echocardiography indicated increased RV wall thickness and RV/LV ratio, and reduced RV fractional shortening, following CPE (CPE+SED vs. SHAM+SED, p<0.05), the last two were improved by exercise training (CPE+EXE vs. CPE+SED, p<0.05). In vivo measures of RV systolic pressure and dP/dtmax increased following CPE (85±10 mmHg and 3317±599 mmHg/s for CPE+SED vs 24±01 mmHg and 1312±68 mmHg/s for SHAM+SED, p<0.05), and were not affected by exercise (p>0.05 vs. CPE+EXE). When adjusted for RV mass, RV contractile function decreased significantly post-CPE, CPE+SED (100±7.7 mm Hg/g) vs SHAM+SED (322±19, p<0.05) and tended to be improved by exercise (CPE+EXE 137±5.5, p>0.05). Conclusion: In rats with CPE and severe pulmonary hypertension, mild exercise training improved aerobic capacity coincident with a trend toward improved RV contractility. These data suggest salutary effects of exercise in chronic thromboembolic pulmonary hypertension.