Abstract 14275: Improvement of Skeletal Muscle Function and Oxidative Capacity, Systemic Inflammation and Growth Hormone/Insulin-Like Growth Factor-1 Signaling in Patients With Advanced Heart Failure Following Ventricular Assist Device Implantation
Background: Impaired skeletal muscle function and metabolism in patients (pts) with heart failure (HF) have been linked to inflammation and growth hormone (GH)/insulin-like growth factor (IGF)-1 axis dysfunction. We hypothesized that hemodynamic improvement following ventricular assist device (VAD) implantation will correct GH/IGF-1 signaling, oxidative metabolism and muscle function in HF.
Methods: Clinical data were obtained from institutional medical records. Blood was collected from controls (46±4 yrs, BMI 26.5±5.3 kg/m2) and pts with HF (55±13 yrs, BMI 27.5±3.3 kg/m2) at VAD implantation and at explantation. Rectus muscle tissue was obtained during VAD implantation and explantation. Serum levels of GH, IGF-1 and TNFα were measured by ELISA. Muscle mRNA expression was analyzed by RT-PCR. Grip strength measurements were performed serially after VAD implantation using a hand dynamometer. Cross-sections of rectus muscle were used for immunostaining for fiber typing and cross-sectional area (CSA) analysis.
Results: GH increased (647±382 pg/ml vs 1371±254 pg/ml in HF; p=0.15) and IGF-1 decreased in HF (5868±1299 pg/ml vs 786±369 pg/ml in HF, p<0.05). After VAD implantation (mean duration 177±146 days), IGF-1 increased 4-fold (2678±751 pg/ml after VAD; p<0.05) but no change was found in levels of GH while muscle mRNA expression of IGF-1 increased 10-fold (p<0.05). Levels of the proinflammatory cytokine TNFα decreased after VAD (4.6±0.9 vs. 2.3±0.4 pg/ml; p<0.05). Grip strength improved by 16.5% at 3 months (p<0.05) after VAD implantation. Increased expression of fatty acid oxidation genes (CD36, CPT1 and PGC1α) was accompanied by a switch towards more oxidative type 1 muscle fibers (38% vs. 52% post-VAD; p<0.05) and increased muscle fiber CSA (+27±8%; p<0.001) compared to pre-VAD.
Conclusion: Our data demonstrate that hemodynamic improvement after VAD implantation corrects GH/IGF-1 signaling, reduces inflammation, increases muscle fiber oxidative capacity and reverses skeletal muscle atrophy and dysfunction in pts with advanced HF. These findings implicate impaired hemodynamics and low cardiac output as central mechanisms contributing to inflammation and muscle dysfunction in advanced HF.
- © 2011 by American Heart Association, Inc.