Anabolic effects of interval exercise training on skeletal muscle of patients with chronic heart failure

Abstract

Purpose: Heart failure (HF) is associated with exercise intolerance and significant skeletal muscle abnormalities. Insulin-like growth factor 1 (IGF-1) is a significant regulator of skeletal muscle mass that promotes muscle hypertrophy. IGF-1 expression is reduced in skeletal muscle of HF patients. Three different IGF-1 isoforms are expressed in humans, namely IGF-1Ea, IGF-1Eb and IGF-1Ec, showing a differential expression pattern in skeletal muscle. Aim of this study was to evaluate the anabolic effect of high intensity interval exercise training program on skeletal muscle and fiber-type distribution of HF patients. Methods: This randomized controlled 2-group study consisted of 9 stable heart failure patients (males, age: 56±13 yrs, BMI: 27±4 kg/m2) who participated in a high intensity interval training rehabilitation program [with (n=5) or without (n=4) the addition of strength training] of 36 sessions, 3 times per week. All patients performed a symptom-limited cardiopulmonary exercise test before and after the completion of the program. At the same time they underwent percutaneous needle biopsies of the vastus lateralis muscle. Pathology measurements included the skeletal muscle fiber type distribution and cross sectional area (CSA) that were determined by adenosine triphosphatase staining. The mRNA expression of IGF-1Ea, IGF-1Eb, IGF-IEc and IGF-1R was investigated by quantitative real-time PCR. Results: After 3 months of exercise training all patients significantly improved their exercise capacity. A significant increase of the CSA of type I fibers from 4519±1071 to 4856±1076 μm2 (p=0.001) and of type II fibers from 4420±1057 to 4925±1049 μm2 (p=0.001) was found and there was a significant reshift to aerobic fibers from 45±9% to 53±7% (p=0.006). An increased expression of the IGF-1Ea, IGF-1Eb and IGF-1Ec transcripts was found following the exercise training compared with the pre-exercise expression levels [1.8±0.9 (p=0.02), 1.7±0.8 (p=0.03) and 2.1±1.4 (p=0.04) fold changes, respectively]. IGF-1R expression levels showed no changes. The percentage increase of CSA found to be correlated with the increase of IGF-1Eb (r=0.72, p=0.03). No significant changes between the two types of exercise were found. Conclusions: The results indicate that high intensity interval exercise training can improve aerobic capacity and may have an anabolic effect by increasing the cross sectional area of muscle fibers in HF patients, possibly via IGF-1 isoform-specific actions. There is also evidence that the pathologic shif to anaerobic fiber phenotype present in HF patients may be reversed by this intervention.