The wasting continuum in heart failure: From sarcopenia to cachexia

Proceedings of the Nutrition Society

Volumn 74, Issue 4, 2015, Pages 367-377

  Von Haehling, Stephan ^a,b  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Cachexia; Fat tissue; Heart failure; Muscle; Sarcopenia; Wasting

Indexed keywords

APPETITE STIMULANT; CYTOCHROME C; ESPINDOLOL; PROTEIN KINASE B; SOMATOMEDIN C; TREVOGRUMAB; UNCLASSIFIED DRUG; ESSENTIAL AMINO ACID; HORMONE;

CACHEXIA; CONFERENCE PAPER; ENZYME PHOSPHORYLATION; FAT MASS; GRIP STRENGTH; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; INCIDENCE; LEAN BODY WEIGHT; MUSCLE MASS; MUSCLE STRENGTH; NONHUMAN; NUTRITIONAL SUPPORT; PHASE 2 CLINICAL TRIAL (TOPIC); PREVALENCE; PROTEIN EXPRESSION; PROTEIN SECRETION; QUALITY OF LIFE; SARCOPENIA; TREADMILL EXERCISE; ADIPOSE TISSUE; APPETITE; COMPLICATION; EXERCISE; METABOLISM; SKELETAL MUSCLE;

ADIPOSE TISSUE; AMINO ACIDS, ESSENTIAL; APPETITE; CACHEXIA; EXERCISE; HEART FAILURE; HORMONES; HUMANS; MUSCLE STRENGTH; MUSCLE, SKELETAL; SARCOPENIA;

EID: 84948380889     PISSN: 00296651     EISSN: 14752719     Source Type: Journal    
DOI: 10.1017/S0029665115002438     Document Type: Conference Paper

References (123)

1. Morley JE, von Haehling S, Anker SD, et al. (2014). From sarcopenia to frailty: a road less traveled. J Cachexia Sarcopenia Muscle. 5, 5-8.
2. Janssen I, Heymsfield SB, Wang ZM, et al. (2000). Skeletal muscle mass, and distribution in 468 men, and women aged 18-88 yr. J Appl Physiol. 89, 81-88.
3. Morley JE, Anker SD, & von Haehling S. (2014). Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology-update 2014. J Cachexia Sarcopenia Muscle. 5, 253-259.
4. Rosenberg IH. (2011). Sarcopenia: origins, and clinical relevance. Clin Geriatr Med. 27, 337-339.
5. Anker SD, Ponikowski P, Varney S, et al. (1997). Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 349, 1050-1053.
6. Doehner W, & Anker SD. (2002). Cardiac cachexia in early literature: a review of research prior to Medline. Int J Cardiol. 85, 7-14.
7. von Haehling S, Morley JE, & Anker SD. (2010). An overview of sarcopenia: facts, and numbers on prevalence, and clinical impact. J Cachexia Sarcopenia Muscle. 1, 129-133.
8. AlchinDR(2014) Sarcopenia: describing rather than defining a condition. J Cachexia SarcopeniaMuscle 5, 265-268.
9. Roubenoff R, Heymsfield SB, Kehayias JJ, et al. (1997). Cannon JG, Rosenberg IH. Standardization of nomenclature of body composition in weight loss. Am J Clin Nutr. 66, 192-196.
10. Narici MV & Maffulli N. (2010). Sarcopenia: characteristics, mechanisms, and functional significance. Br Med Bull. 95, 139-159.
11. Barbat-Artigas S, Plouffe S, Pion CH, et al. (2013). Toward a sex-specific relationship between muscle strength, and appendicular lean body mass index?. J Cachexia Sarcopenia Muscle. 4, 137-144.
12. Goodman MJ, Ghate SR, Mavros P, et al. (2013). Development of a practical screening tool to predict low muscle mass using NHANES 1999-2004. J Cachexia Sarcopenia Muscle 4, 187-197.
13. Villani AM, Miller MD, Cameron ID, et al. (2013). Development, and relative validity of a new field instrument for detection of geriatric cachexia: preliminary analysis in hip fracture patients. J Cachexia Sarcopenia Muscle. 4, 209-216.
14. von Haehling S, Steinbeck L, Doehner W, et al. (2013). Muscle wasting in heart failure: an overview. Int J Biochem Cell Biol. 45, 2257-2265.
15. Anker SD, Coats AJ, Morley JE, et al. (2014). Muscle wasting disease: a proposal for a new disease classification. J Cachexia Sarcopenia Muscle. 5, 1-3.
16. Abellan van Kan G. (2009). Epidemiology, and consequences of sarcopenia. J Nutr Health Aging. 13, 708-712.
17. Doherty TJ. (2003). Invited review: aging, and sarcopenia. J Appl Physiol. 95, 1717-1727.
18. Morley JE, Kim MJ, Haren MT, et al. (2005). Frailty, and the aging male. Aging Male. 8, 135-140.
19. Fearon K, Evans WJ, & Anker SD. (2011). Myopenia-A new universal term for muscle wasting. J Cachexia Sarcopenia Muscle 2, 1-3.
20. Fülster S, Tacke M, Sandek A, et al. (2013). Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Eur Heart J. 34, 512-519.
21. Anker SD, Ponikowski PP, Clark AL, et al. (1999). Cytokines, and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J. 20, 683-693.
22. Farkas J, von Haehling S, Kalantar-Zadeh K, et al. (2013). Cachexia as a major public health problem: frequent, costly, and deadly. J Cachexia Sarcopenia Muscle. 4, 173-178.
23. Ebner N, Elsner S, Springer J, et al. (2013). Molecular mechanisms, and treatment targets of muscle wasting, and cachexia in heart failure: an overview. Curr Opin Support Palliat Care. 8, 15-24.
24. Hopkinson JB. (2014). Psychosocial impact of cancer cachexia. J Cachexia Sarcopenia Muscle 5, 89-94.
25. Wanger T, Foster NR, Nguyen PL, et al. (2014). Patients'rationale for declining participation in a cancer-Associated weight loss study. J Cachexia Sarcopenia Muscle. 5, 121-125.
26. Vaughan VC, Martin P, & Lewandowski PA. (2013). Cancer cachexia: impact, mechanisms, and emerging treatments. J Cachexia Sarcopenia Muscle. 4, 95-109.
27. Argilès JM, Fontes-Oliveira CC, Toledo M, et al. (2014). Cachexia: a problem of energetic inefficiency. J Cachexia Sarcopenia Muscle. 5, 279-286.
28. Yoshida T, & Delafontaine P. (2015). Mechanisms of cachexia in chronic disease states. Am J Med Sci (In the Press
29. Dirks AJ, & Leeuwenburgh C. (2005). The role of apoptosis in age-related skeletal muscle atrophy. Sports Med. 35, 473-483.
30. Malmstrom TK, Miller DK, Herning MM, et al. (2013). Low appendicular skeletal muscle mass (ASM) with limited mobility, and poor health outcomes in middle-Aged African Americans. J Cachexia Sarcopenia Muscle. 4, 179-186.
31. Janssen HC, Samson MM, Meeuwsen IB, et al. (2004). Strength, mobility, and falling in women referred to a geriatric outpatient clinic. Aging Clin Exp Res. 16, 122-125.
32. Janssen I, Baumgartner RN, Ross R, et al. (2004). Skeletal muscle cutpoints associated with elevated physical disability risk in older men, and women. Am J Epidemiol. 159, 413-421.
33. Muiller-Hocker J. (1988). Morphologie, Cytochemie und Immunhistochemie des Cytochrom-c-oxidase-Mangels. Verh Dtsch Ges Pathol. 72, 552-565.
34. Ranvier L. (1873). Proprietès et structures diffèrentes des muscles rouges et des muscles blancs chez les lapins et chez les raies. Cr Acad Sci Paris. 77, 1030-1034.
35. Hultman E. (1995). Fuel selection, muscle fibre. Proc Nutr Soc. 54, 107-121.
36. Daugaard JR, & Richter EA. (2001). Relationship between muscle fibre composition, glucose transporter protein 4, and exercise training: possible consequences in non-insulindependent diabetes mellitus. Acta Physiol Scand. 171, 267-276.
37. Lexell J, Taylor CC, & SjöströmM(1988) What is the cause of the ageing atrophy?. Total number, size, and proportion of different fiber types studied in whole vastus lateralis muscle from 15- To 83-year-old men. J Neurol Sci. 84, 275-294.
38. Lexell J. (1995). Human aging, muscle mass, and fiber type composition. J Gerontol A, Biol Sci Med Sci. 50, 11-16.
39. Campbell MJ, McComas AJ, Petito F, et al. (1973). Physiological changes in ageing muscles. J Neurol Neurosurg Psychiatry. 36, 174-182.
40. Borkan GA, Hults DE, Gerzof SG, et al. (1983). Age changes in body composition revealed by computed tomography. J Gerontol. 38, 673-677.
41. Overend TJ, Cunningham DA, Paterson DH, et al. (1992). Thigh composition in young, and elderly men determined by computed tomography. Clin Physiol. 12, 629-640.
42. Taaffe DR, Henwood TR, Nalls MA, et al. (2009). Alterations in muscle attenuation following detraining, and retraining in resistance-Trained older adults. Gerontology. 55, 217-223.
43. Cadenas E, & Davies KJ. (2000). Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 29, 222-230.
44. PollackM& Leeuwenburgh C. (2001). Apoptosis, and aging: role of the mitochondria. J Gerontol A, Biol Sci Med Sci. 56, B475-B482.
45. Drew B, Phaneuf S, Dirks A, et al. (2003). Effects of aging, and caloric restriction on mitochondrial energy production in gastrocnemius muscle, and heart. Am J Physiol Regul Integr Comp Physiol. 284, R474-R480.
46. von Haehling S, Genth-Zotz S, Anker SD, et al. (2002). Cachexia: a therapeutic approach beyond cytokine antagonism. Int J Cardiol. 85, 173-183.
47. Barton-Davis ER, Shoturma DI, & Sweeney HL. (1999). Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle. Acta Physiol Scand. 167, 301-305.
48. Murton AJ, Constantin D, & Greenhaff PL. (2008). The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling, and atrophy. Biochim Biophys Acta 1782, 730-743.
49. Loncar G, Fülster S, von Haehling S, et al. (2013). Metabolism, and the heart: an overview of muscle, fat, and bone metabolism in heart failure. Int J Cardiol. 162, 77-85.
50. Tacke M, Ebner N, Boschmann M, et al. (2013). Resting energy expenditure, and the effects of muscle wasting in patients with chronic heart failure: results from the Studies Investigating Comorbidities Aggravating Heart Failure (SICA-HF). J Am Med Dir Assoc. 14, 837-841.
51. Cicoira M, Zanolla L, Franceschini L, et al. (2001). Skeletal muscle mass independently predicts peak oxygen consumption, and ventilatory response during exercise in noncachectic patients with chronic heart failure. J Am Coll Cardiol. 37, 2080-2085.
52. Coats AJS. (1996). The "muscle hypothesis" of chronic heart failure. J Mol Cell Cardiol. 28, 2255-2262.
53. Sullivan MJ, Green HJ, & Cobb FR. (1990). Skeletal muscle biochemistry, and histology in ambulatory patients with long-Term heart failure. Circulation. 81, 518-527.
54. Mancini DM, Walter G, Reichek N, et al. (1992). Contribution of skeletal muscle atrophy to exercise intolerance, and altered muscle metabolism in heart failure. Circulation. 85, 1364-1373.
55. Drexler H, Riede U, Münzel T, et al. (1992). Alterations of skeletal muscle in chronic heart failure. Circulation. 85, 1751-1759.
56. Lipkin DP, Jones DA, Round JM, et al. (1988). Abnormalities of skeletal muscle in patients with chronic heart failure. Int J Cardiol. 18, 187-195.
57. Vescovo G, & Dalla Libera L. (2006). Skeletal muscle apoptosis in experimental heart failure: the only link between inflammation, and skeletal muscle wastage?. Curr Opin Clin Nutr Metab Care 9, 416-422.
58. Adams V, Jiang H, Yu J, et al. (1999). Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. J Am Coll Cardiol. 33, 959-965.
59. Harrington D, Anker SD, Chua TP, et al. (1997). Skeletal muscle function, and its relation to exercise tolerance in chronic heart failure. J Am Coll Cardiol. 30, 1758-1764.
60. Gielen S, Sandri M, Kozarez I, et al. (2012). Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig Exercise Intervention in Chronic Heart Failure, and Aging catabolism study. Circulation. 125, 2716-2727.
61. Hambrecht R, Schulze PC, Gielen S, et al. (2002). Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure. J Am Coll Cardiol. 39, 1175-1181.
62. Toth MJ, Ward K, van der Velden J, et al. (2011). Chronic heart failure reduces Akt phosphorylation in human skeletal muscle: relationship to muscle size, and function. J Appl Physiol. 110, 892-900.
63. Cicoira M, Kalra PR, & Anker SD. (2003). Growth hormone resistance in chronic heart failure, and its therapeutic implications. J Card Fail. 9, 219-226.
64. Anker SD, & von Haehling S. (2004). Inflammatory mediators in chronic heart failure: an overview. Heart. 90, 464-470.
65. Ferrari R, Bachetti T, Confortini R, et al. (1995). Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation. 92, 1479-1486.
66. Rauchhaus M, Doehner W, Francis DP, et al. (2000). Plasma cytokine parameters, and mortality in patients with chronic heart failure. Circulation. 102, 3060-3067.
67. Khawaja T, Chokshi A, Ji R, et al. (2014). 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. J Cachexia Sarcopenia Muscle. 5, 297-305.
68. Melenovsky V, Kotrc M, Borlaug BA, et al. (2013). Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol. 62, 1660-1670.
69. Christensen HM, Kistorp C, Schou M, et al. (2014). Cross-Talk between the heart, and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: a prospective study. Metabolism. 63, 141-149.
70. Szabò T, Postrach E, Mähler A, et al. (2013). Increased catabolic activity in adipose tissue of patients with chronic heart failure. Eur J Heart Fail. 15, 1131-1137.
71. Tanaka T, Tsutamoto T, Sakai H, et al. (2008). Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail. 10, 360-366.
72. Lyon CJ, Law RE, & Hsueh WA. (2003). Minireview: adiposity, inflammation, and atherogenesis. Endocrinology. 144, 2195-2200.
73. Arita Y, Kihara S, Ouchi N, et al. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 257, 79-83.
74. Lavie CJ, Osman AF, Milani RV, et al. (2003). Body composition, and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol. 91, 891-894.
75. Lenk K, Erbs S, Höllriegel R, et al. (2012). Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Prev Cardiol. 19, 404-411.
76. Cunha TF, Bacurau AV, Moreira JB, et al. (2012). Exercise training prevents oxidative stress, and ubiquitin-proteasome system overactivity, and reverse skeletal muscle atrophy in heart failure. PLoS ONE. 7, e41701.
77. Smart NA, & SteeleM(2011) The effect of physical training on systemic proinflammatory cytokine expression in heart failure patients: a systematic review. Congest Heart Fail. 17, 110-114.
78. Gould DW, Lahart I, Carmichael AR, et al. (2013). Cancer cachexia prevention via physical exercise: molecular mechanisms. J Cachexia Sarcopenia Muscle. 4, 111-124.
79. Sasso JP, Eves ND, Christensen JF, et al. (2015) A framework for prescription in exercise-oncology research. J Cachexia Sarcopenia Muscle 6, 115-124.
80. McMurray JJ, Adamopoulos S, Anker SD, et al. (2012). ESC Guidelines for the diagnosis, and treatment of acute, and chronic heart failure 2012: the Task Force for the Diagnosis, and Treatment of Acute, and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 14, 803-869.
81. O'Connor CM, Whellan DJ, Lee KL, et al. (2009). Efficacy, and safety of exercise training in patients with chronic heart failure: HFACTION randomized controlled trial. J Am Med Assoc. 301, 1439-1450.
82. Piepoli MF, Conraads V, Corrà U, et al. (2011). Exercise training in heart failure: from theory to practice A consensus document of the Heart Failure Association, and the European Association for Cardiovascular Prevention, and Rehabilitation. Eur J Heart Fail. 13, 347-357.
83. Ebner N, Elsner S, Springer J, et al. (2014). Molecular mechanisms, and treatment targets of muscle wasting, and cachexia in heart failure: an overview. Curr Opin Support Palliat Care. 8, 15-24.
84. Anker MS, von Haehling S, Springer J, et al. (2013). Highlights of the mechanistic, and therapeutic cachexia, and sarcopenia research 2010 to 2012, and their relevance for cardiology. Int J Cardiol. 162, 73-76.
85. Wakabayashi H, & Sakuma K. (2014). Rehabilitation nutrition for sarcopenia with disability: a combination of both rehabilitation, and nutrition care management. J Cachexia Sarcopenia Muscle. 5, 269-277.
86. Osterziel KJ, Strohm O, Schuler J, et al. (1998). Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet. 351, 1233-1237.
87. Ryall JG, & Lynch GS. (2008). The potential, and the pitfalls of beta-Adrenoceptor agonists for the management of skeletal muscle wasting. Pharmacol Ther. 120, 219-232.
88. Busquets S, Toledo M, Penna F, et al. (2014). Complete reversal on muscle wasting in an animal model of cancer cachexia: additive effects of myostatin inhibition, and beta-2 agonist treatment. J Cachexia Sarcopenia Muscle. 5, 35-78 (Abstract
89. Toledo M, Springer J, Busquets S, et al. (2014). Formoterol in the treatment of experimental cancer cachexia: effects on heart function. J Cachexia Sarcopenia Muscle 5, 315-320.
90. Aquilani R, Opasich C, Gualco A, et al. (2008). Adequate energy-protein intake is not enough to improve nutritional, and metabolic status in muscle-depleted patients with chronic heart failure. Eur J Heart Fail. 10, 112711-112735.
91. Banerjee P, Caulfield B, Crowe L, et al. (2009). Prolonged electrical muscle stimulation exercise improves strength, peak VO2, and exercise capacity in patients with stable chronic heart failure. J Card Fail. 15, 319-326.
92. Volterrani M, Rosano G, & Iellamo F. (2012). Testosterone, and heart failure. Endocrine. 42, 272-277.
93. Josiak K, Jankowska EA, Piepoli MF, et al. (2014). Skeletal myopathy in patients with chronic heart failure: significance of anabolic-Androgenic hormones. J Cachexia Sarcopenia Muscle. 5, 287-296.
94. Jankowska EA, Biel B, Majda J, et al. (2006). Anabolic deficiency in men with chronic heart failure: prevalence, and detrimental impact on survival. Circulation. 114, 1829-1837.
95. Caminiti G, Volterrani M, Iellamo F, et al. (2009). Effect of long-Acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 54, 919-927.
96. Iellamo F, Volterrani M, Caminiti G, et al. (2010). Testosterone therapy in women with chronic heart failure: a pilot double-blind, randomized, placebo-controlled study. J Am Coll Cardiol. 56, 1310-1316.
97. Takagi KI, Horie K, Fujita E, et al. (2013). Anabolic effect of A Novel Long-Acting SARM in Rat ORX model. J Cachexia Sarcopenia Muscle. 4, 295-343 (Abstract
98. Dobs AS, Boccia RV, Croot CC, et al. (2013). Effects of enobosarm on muscle wasting, and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 14, 335-345.
99. Basaria S, Collins L, Dillon EL, et al. (2013). The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A, Biol SciMed Sci. 68, 87-95.
100. Papanicolaou DA, Ather SN, Zhu H, et al. (2013) A phase IIA randomized, placebo-controlled clinical trial to study the efficacy, and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J Nutr Health Aging. 17, 533-543.
101. Crawford J, Dalton JT, Hancock ML, et al. (2014). Enobosarm, a selective androgen receptor modulator (SARM), increases lean body mass (LBM) in advanced non-small cell lung cancer patients in two pivotal, international Phase 3 trials. J Cachexia Sarcopenia Muscle. 5, 35-78 (Abstract
102. von Haehling S, Lainscak M, Springer J, et al. (2009). Cardiac cachexia: a systematic overview. Pharmacol Ther. 121, 227-252.
103. von Haehling S, Anker SD. (2014). Prevalence, incidence, and clinical impact of cachexia: facts, and numbers-update 2014. J Cachexia Sarcopenia Muscle 5, 261-263.
104. Rozentryt P, von Haehling S, Lainscak M, et al. (2010). The effects of a high-caloric protein-rich oral nutritional supplement in patients with chronic heart failure, and cachexia on quality of life, body composition, and inflammation markers: a randomized, double-blind pilot study. J Cachexia Sarcopenia Muscle. 1, 35-42.
105. Kojima M, Hosoda H, Date Y, et al. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 402, 656-660.
106. Date Y, Kojima M, Hosoda H, et al. (2000). Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats, and humans. Endocrinology. 141, 4255-4261.
107. Blum D, Oberholzer R, de Wolf-Linder S, et al. (2013). Individually dose-optimized Phase I-II study with natural ghrelin in advanced cancer patients with cachexia. J Cachexia Sarcopenia Muscle 4, 295-343 (Abstract
108. Nagaya N, Uematsu M, Kojima M, et al. (2001). Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin, and anabolic/catabolic factors. Circulation. 104, 2034-2038.
109. Nagaya N, Moriya J, Yasumura Y, et al. (2004). Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation. 110, 3674-3679.
110. Nagaya N, Uematsu M, Kojima M, et al. (2001). Chronic administration of ghrelin improves left ventricular dysfunction, and attenuates development of cardiac cachexia in rats with heart failure. Circulation. 104, 1430-1435.
111. Palus S, von Haehling S, Doehner W, et al. (2013). Effect of application route of the ghrelin analog BIM-28131 (RM-131) on body weight, and body composition in a rat heart failure model. Int J Cardiol. 168, 2369-2374.
112. Lenk K, Palus S, Schur R, et al. (2013). Effect of ghrelin, and its analogues, BIM-28131, and BIM-28125, on the expression of myostatin in a rat heart failure model. J Cachexia Sarcopenia Muscle. 4, 63-69.
113. Chen JA, Guillory B, Zhang G, et al. (2013). Ghrelin prevents cancer-related muscle wasting through GHSRindependent regulation of myostatin, and p38. J Cachexia Sarcopenia Muscle. 4, 295-343 (Abstract
114. Palus S, Schur R, Akashi YJ, et al. (2011). Ghrelin, and its analogues, BIM-28131, and BIM-28125, improve body weight, and regulate the expression of MuRF-1, and MAFbx in a rat heart failure model. PLoS ONE. 6, e26865.
115. Garcia JM, Friend J, & Allen S. (2013). Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support Care Cancer. 21, 129-237.
116. Garcia JM, Boccia RV, Graham CD, et al. (2015). Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebocontrolled, double-blind trials. Lancet Oncol. 16, 108-116.
117. Abernethy A, Temel J, Currow D, et al. (2013). Anamorelin HCl for the treatment of anorexia-cachexia in lung cancer: study design, and baseline characteristics of patients in the phase III clinical trial ROMANA 2 (HT-ANAM-302). J Cachexia Sarcopenia Muscle. 4, 295-343 (Abstract
118. Pietra C, Takeda Y, Tazawa-Ogata N, et al. (2014). Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile. J Cachexia Sarcopenia Muscle. 5, 329-337.
119. Bauerlein R, Pangilinan J, Salzler R, et al. (2013). Efficacy of REGN1033, a fully human anti-myostatin antagonist antibody, in rodent muscle function. J Cachexia Sarcopenia Muscle 4, 295-343 (Abstract
120. Stewart Coats AJ, Srinivasan V, Surendran J, et al. (2011). The ACT-ONE trial, a multicentre, randomised, doubleblind, placebo-controlled, dose-finding study of the anabolic/.catabolic transforming agent, MT-102 in subjects with cachexia related to stage III, and IV non-small cell lung cancer, and colorectal cancer: study design. J Cachexia Sarcopenia Muscle. 2, 201-207.
121. Stewart Coats AJ, Fuang HG, Prabbash K., et al. (2014). Espindolol for the treatment, and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer (ACT-ONE): randomised, double-blind, placebo-controlled, international multi-centre phase II study. J Cachexia SarcopeniaMuscle. 5, 35-78 (Abstract
122. Evans WJ, Morley JE, Argilès J, et al. (2008). Cachexia: a new definition. Clin Nutr. 27, 793-799.
123. Morley JE, Abbatecola AM, Argiles JM, et al. (2011). Society on Sarcopenia, Cachexia, and Wasting Disorders Trialist Workshop.Sarcopeniawith limitedmobility: an international consensus. J AmMed Dir Assoc. 12, 403-409.