Ventricular assist device implantation improves skeletal muscle function, oxidative capacity, and growth hormone/insulin‐like growth factor‐1 axis signaling in patients with advanced heart failure

Journal of Cachexia, Sarcopenia and Muscle

Khawaja Tuba¹  Chokshi Aalap¹  Ji Ruiping¹  Kato Tomoko S.¹  Xu Katherine¹  Zizola Cynthia¹  Wu Christina¹  Forman Daniel E.¹  Ota Takeyoshi²  Kennel Peter¹  Takayama Hiroo¹  Naka Yoshifumi¹  George Isaac¹  Mancini Donna¹ 

[1] Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology, Columbia University Medical Center, New York, NY;Department of Surgery, Division of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY

关键词: Skeletal muscle;    Heart failure;    Cardiovascular surgery;    Metabolism;    Growth factors;   

DOI  :  10.1007/s13539-014-0155-9

来源: Wiley

【 摘 要 】

Abstract

Background

Skeletal muscle dysfunction in patients with heart failure (HF) has been linked to impaired growth hormone (GH)/insulin-like growth factor (IGF)-1 signaling. We hypothesized that ventricular assist device (VAD) implantation reverses GH/IGF-1 axis dysfunction and improves muscle metabolism in HF.

Methods

Blood and rectus abdominis muscle samples were collected during VAD implantation and explantation from patients with HF and controls. Clinical data were obtained from medical records, biomarkers measured by enzyme-linked immunosorbent assay (ELISA), and gene expression analyzed by reverse transcription and real-time polymerase chain reaction (RT-PCR). Grip strength was assessed by dynamometry. Oxidative capacity was measured using oleate oxidation rates. Muscle fiber type and size were assessed by histology.

Results

Elevated GH (0.27 ± 0.27 versus 3.6 ± 7.7 ng/ml in HF; p = 0.0002) and lower IGF-1 and insulin-like growth factor binding protein (IGFBP)-3 were found in HF (IGF-1, 144 ± 41 versus 74 ± 45 ng/ml in HF, p < 0.05; and IGFBP-3, 3,880 ± 934 versus 1,935 ± 862 ng/ml in HF, p = 0.05). The GH/IGF-1 ratio, a marker of GH resistance, was elevated in HF (0.002 ± 0.002 versus 0.048 ± 0.1 pre-VAD; p < 0.0039). After VAD support, skeletal muscle expression of IGF-1 and IGFBP-3 increased (10-fold and 5-fold, respectively; p < 0.05) accompanied by enhanced oxidative gene expression (CD36, CPT1, and PGC1α) and increased oxidation rates (+1.37-fold; p < 0.05). Further, VAD implantation increased the oxidative muscle fiber proportion (38 versus 54 %, p = 0.031), fiber cross-sectional area (CSA) (1,005 ± 668 versus 1,240 ± 670 μm², p < 0.001), and Akt phosphorylation state in skeletal muscle. Finally, hand grip strength increased 26.5 ± 27.5 % at 180 days on-VAD (p < 0.05 versus baseline).

Conclusion

Our data demonstrate that VAD implantation corrects GH/IGF-1 signaling, improves muscle structure and function, and enhances oxidative muscle metabolism in patients with advanced HF.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.