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

详细信息    查看全文

• 作者：Tuba Khawaja (1)
  Aalap Chokshi (1)
  Ruiping Ji (1)
  Tomoko S. Kato (1)
  Katherine Xu (1)
  Cynthia Zizola (1)
  Christina Wu (1)
  Daniel E. Forman (1) (3)
  Takeyoshi Ota (2)
  Peter Kennel (1)
  Hiroo Takayama (1) (2)
  Yoshifumi Naka (1) (2)
  Isaac George (1) (2)
  Donna Mancini (1)
  Christian P. Schulze (1)
  
• 关键词：Skeletal muscle ; Heart failure ; Cardiovascular surgery ; Metabolism ; Growth factors
• 刊名：Journal of Cachexia, Sarcopenia and Muscle
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：5
• 期：4
• 页码：297-305
• 全文大小：609 KB
• 参考文献：1. Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation. 1997;96:526-4. CrossRef
  2. Schulze PC, Kratzsch J, Linke A, Schoene N, Adams V, Gielen S, et al. Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. Eur J Heart Fail. 2003;5(1):33-0. CrossRef
  3. Schulze PC, Biolo A, Gopal D, Shahzad K, Balog J, Fish M, et al. Dynamics in insulin resistance and plasma levels of adipokines in patients with acute decompensated and chronic stable heart failure. J Card Fail. 2011;17(12):1004-1. CrossRef
  4. Duscha BD, Schulze PC, Robbins JL, Forman DE. Implications of chronic heart failure on peripheral vasculature and skeletal muscle before and after exercise training. Heart Fail Rev. 2008;13(1):21-7. CrossRef
  5. Drexler H, Riede U, Munzel T, Konig H, Funke E, Just H. Alterations of skeletal muscle in chronic heart failure. Circulation. 1992;85(5):1751-. CrossRef
  6. Habedank D, Meyer FJ, Hetzer R, Anker SD, Ewert R. Relation of respiratory muscle strength, cachexia and survival in severe chronic heart failure. J Cachex Sarcopenia Muscle. 2013;4(4):277-5. CrossRef
  7. Tsutsui H, Ide T, Hayashidani S, Suematsu N, Shiomi T, Wen J, et al. Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure. Circulation. 2001;104(2):134-. CrossRef
  8. Simonini A, Chang K, Yue P, Long CS, Massie BM. Expression of skeletal muscle sarcoplasmic reticulum calcium-ATPase is reduced in rats with postinfarction heart failure. Heart. 1999;81(3):303-. CrossRef
  9. Duscha BD, Kraus WE, Keteyian SJ, Sullivan MJ, Green HJ, Schachat FH, et al. Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations. J Am Coll Cardiol. 1999;33(7):1956-3. CrossRef
  10. Junnila RK, List EO, Berryman DE, Murrey JW, Kopchick JJ. The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol. 2013;9(6):366-6. CrossRef
  11. Anker SD, Volterrani M, Pflaum CD, Strasburger CJ, Osterziel KJ, Doehner W, et al. Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone. J Am Coll Cardiol. 2001;38(2):443-2. CrossRef
  12. Hambrecht R, Schulze PC, Gielen S, Linke A, Mobius-Winkler S, Yu J, et al. Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure. J Am Coll Cardiol. 2002;39(7):1175-1. CrossRef
  13. Song YH, Li Y, Du J, Mitch WE, Rosenthal N, Delafontaine P. Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting. J Clin Invest. 2005;115(2):451-. CrossRef
  14. Osterziel KJ, Strohm O, Schuler J, Friedrich M, Hanlein D, Willenbrock R, et al. Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet. 1998;351(9111):1233-. CrossRef
  15. Hambrecht R, Schulze PC, Gielen S, Linke A, Mobius-Wink
• 作者单位：Tuba Khawaja (1)
  Aalap Chokshi (1)
  Ruiping Ji (1)
  Tomoko S. Kato (1)
  Katherine Xu (1)
  Cynthia Zizola (1)
  Christina Wu (1)
  Daniel E. Forman (1) (3)
  Takeyoshi Ota (2)
  Peter Kennel (1)
  Hiroo Takayama (1) (2)
  Yoshifumi Naka (1) (2)
  Isaac George (1) (2)
  Donna Mancini (1)
  Christian P. Schulze (1)
  
  1. Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology, Columbia University Medical Center, 622 West 168th Street, PH 10, Room 203, New York, NY, 10032, USA
  3. Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  2. Department of Surgery, Division of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY, USA
  
• ISSN：2190-6009

文摘

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?±-.27 versus 3.6?±-.7?ng/ml in HF; p--.0002) and lower IGF-1 and insulin-like growth factor binding protein (IGFBP)-3 were found in HF (IGF-1, 144?±-1 versus 74?±-5?ng/ml in HF, p--.05; and IGFBP-3, 3,880?±-34 versus 1,935?±-62?ng/ml in HF, p--.05). The GH/IGF-1 ratio, a marker of GH resistance, was elevated in HF (0.002?±-.002 versus 0.048?±-.1 pre-VAD; p--.0039). After VAD support, skeletal muscle expression of IGF-1 and IGFBP-3 increased (10-fold and 5-fold, respectively; p--.05) accompanied by enhanced oxidative gene expression (CD36, CPT1, and PGC1α) and increased oxidation rates (+1.37-fold; p--.05). Further, VAD implantation increased the oxidative muscle fiber proportion (38 versus 54?%, p--.031), fiber cross-sectional area (CSA) (1,005?±-68 versus 1,240?±-70?μm2, p--.001), and Akt phosphorylation state in skeletal muscle. Finally, hand grip strength increased 26.5?±-7.5?% at 180?days on-VAD (p--.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.