Short-Term Moderate Aerobic Exercise Training Improves the Endothelium-Dependent Vasorelaxation in Chronic Heart Failure: Role of Extracellular Superoxide Dismutase.

Moderate aerobic exercise training (ET) has been shown to improve endothelial dysfunction in chronic heart failure (CHF). However, it is unclear whether this beneficial effect is related to reduced oxidative degradation of nitric oxide. The aim of the study was to demonstrate whether extracellular superoxide dismutase (ec-SOD)- the major antioxidant enzyme system of the vessel wall- may be improved after exercise training, and whether this effect may be associated with enhanced endothelium-dependent vasorelaxation in CHF. We studied 72 patients with NYHA class II and III CHF patients (mean age 65 ± 9 years) due to ischemic cardiomyopathy (ejection fraction 38 ± 8%). Inclusion criteria were clinical stability in the last 3 months and ability to exercise. Patients were randomized into 2 matched groups. A group (T, n = 40) underwent a supervised ET at 70% of peak VO2, 3 times a week for 8 weeks. A group (NT, n = 32) was not exercised. Medications were not changed during the study. On study entry and at 8 weeks all patients underwent a symptom-limited cardiopulmonary exercise testing, brachial artery endothelium-dependent (ED) vasomotor response, and measurement of endothelium-bound ec-SOD activity, released in plasma upon heparin bolus injection. Of 72 patients, 58 completed the study. Peak VO2 and VE/VCO2 slope were significantly improved in trained patients (from 15.9 ± 3 mL/kg/min to 18.1 ± 3.2 mL/kg/min, and from 43 ± 9 to 36 ± 10, respectively, P < 0.001 vs NT for both). No changes were observed in untrained controls. In trained patients, flow-mediated dilation (FMD) improved significantly (from 4.6 ± 3% to 6.3 ± 3.2%, P < 0.01 vs NT), and ec-SOD activity improved as well (from 16.8 ± 10 USOD mL/min to 20.9 ± 12 USOD mL/min, P < 0.001 vs NT). Changes in ec-SOD activity was correlated with both changes in flow-mediated dilation (r = 0.61,P < 0.001) and changes in peak VO2 (r = 0.48,P < 0.05). Patients with ec-SOD levels <200 USOD mL/min at baseline had greater improvements in FMD after ET than patients with ec-SOD levels > 200. In conclusion, moderate aerobic ET improves ec-SOD activity in CHF patients. This effect is related to both enhanced endothelium-dependent vasorelaxation and functional capacity.