Abstract 3196: Regular Physical Exercise Training Induces Neovascularization in the Skeletal Muscle in Patients with Severe Chronic Heart Hailure
Patients (pts) with chronic heart failure (CHF) are limited in their exercise capacity, in particular due to peripheral alterations. Inflammatory activation in advanced stages of the disease was recently shown to contribute to a loss of capillary density in the skeletal muscle. Given that bone marrow-derived stem cells promote endogenous tissue regeneration, aim of the present study was to determine, whether physical exercise training influences capillary density in the skeletal muscle through activation of circulating endothelial progenitor cells (EPCs) in pts with CHF and whether this impacts on exercise capacity.
Methods: 37 pts with CHF (LVEF24 ±2 %, NYHA class IIIb) were randomized to 6 months of exercise training (30 min bicycle ergometer training daily at 50 – 60% of maximal work load) or sedentary lifestyle (control). At begin, after 3 and 6 months, blood samples and a biopsy of the vastus lateralis muscle were obtained, and a spiroergometry was performed. The number of circulating CD34/KDR+ EPCs was counted using FACS analysis. Capillary density and number of CD34+ cells in skeletal muscle were quantified by immunohistochemistry.
Results: In the training group the number of CD34/KDR+ EPCs in the blood increased by 83% after 3 months and by 79% after 6 months (p<0.05 for Δ after 3 and 6 months versus begin and control). This was associated with an augmentation in capillary density by 14% after 3 months and 15% after 6 months (p<0.05 for 3 and 6 months versus begin and control), which was partially the result of an enhanced homing of CD34+ cells in skeletal muscle (from 5.8 ± 0.34 at begin to 7.3 ± 0.32 after 3 months and 7.6 ± 0.33 cells per high-power field, p<0.05 vs. control for the change). This was accompanied by an improvement in peak oxygen uptake by 16% after 3 months (from 15.3±0.8 to 17.8±0.8 ml/min/kg) and by 24% after 6 months (to 19.0±0.7 ml/min/kg; p<0.05 for 3 and 6 months versus begin and control). All above mentioned parameters remained unchanged in the control group.
Conclusion: In pts with severe CHF, regular exercise training leads to a neovascularization of the skeletal muscle. This training-induced improvement of muscle vascularization might be partially the result of an increase in number of EPCs and is associated with an improvement in exercise capacity.