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Implications of chronic heart failure on peripheral vasculature and skeletal muscle before and after exercise training

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Abstract

 The pathophysiology of chronic heart failure (CHF) is typically conceptualized in terms of cardiac dysfunction. However, alterations in peripheral blood flow and intrinsic skeletal muscle properties are also now recognized as mechanisms for exercise intolerance that can be modified by therapeutic exercise. This overview focuses on blood delivery, oxygen extraction and utilization that result from heart failure. Related features of inflammation, changes in skeletal muscle signaling pathways, and vulnerability to skeletal muscle atrophy are discussed. Specific focus is given to the ways in which perfusion and skeletal muscle properties affect exercise intolerance and how peripheral improvements following exercise training increase aerobic capacity. We also identify gaps in the literature that may constitute priorities for further investigation.

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References

  1. Pina IL, Apstein CS, Balady GJ, Belardinelli R, Chaitman BR, Duscha BD, Fletcher BJ, Fleg JL, Myers JN, Sullivan MJ (2003) Exercise and heart failure: a statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation 107:1210–1225

    PubMed  Google Scholar 

  2. Higginbotham MB, Morris KG, Conn EH, Coleman RE, Cobb FR (1983) Determinants of variable exercise performance among patients with severe left ventricular dysfunction. Am J Cardiol 51:52–60

    PubMed  CAS  Google Scholar 

  3. Szlachcic J, Massie BM, Kramer BL, Topic N, Tubau J (1985) Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 55:1037–1042

    PubMed  CAS  Google Scholar 

  4. Franciosa JA, Park M, Levine TB (1981) Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 47:33–39

    PubMed  CAS  Google Scholar 

  5. Maskin CS, Forman R, Sonnenblick EH, Frishman WH, LeJemtel TH (1983) Failure of dobutamine to increase exercise capacity despite hemodynamic improvement in severe chronic heart failure. Am J Cardiol 51:177–182

    PubMed  CAS  Google Scholar 

  6. Wilson JR, Martin JL, Ferraro N, Weber KT (1983) Effect of hydralazine on perfusion and metabolism in the leg during upright bicycle exercise in patients with heart failure. Circulation 68:425–432

    PubMed  CAS  Google Scholar 

  7. Wilson JR, Martin JL, Ferraro N (1984) Impaired skeletal muscle nutritive flow during exercise in patients with congestive heart failure: role of cardiac pump dysfunction as determined by the effect of dobutamine. Am J Cardiol 53:1308–1315

    PubMed  CAS  Google Scholar 

  8. Sullivan MJ, Higginbotham MB, Cobb FR (1988) Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation 77:552–559

    PubMed  CAS  Google Scholar 

  9. Wiener DH, Fink LI, Maris J, Jones RA, Chance B, Wilson JR (1986) Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow. Circulation 73:1127–1136

    PubMed  CAS  Google Scholar 

  10. Massie B, Conway M, Yonge R, Frostick S, Ledingham J, Sleight P, Radda G, Rajagopalan B (1987) Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow. Circulation 76:1009–1019

    PubMed  CAS  Google Scholar 

  11. Massie BM, Conway M, Rajagopalan B, Yonge R, Frostick S, Ledingham J, Sleight P, Radda G (1988) Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow. Circulation 78:320–326

    PubMed  CAS  Google Scholar 

  12. Wilson JR, Mancini DM, Dunkman WB (1993) Exertional fatigue due to skeletal muscle dysfunction in patients with heart failure. Circulation 87:470–475

    PubMed  CAS  Google Scholar 

  13. Duscha BD, Annex BH, Green HJ, Pippen AM, Kraus WE (2002) Deconditioning fails to explain peripheral skeletal muscle alterations in men with chronic heart failure. J Am Coll Cardiol 39:1170–1174

    PubMed  Google Scholar 

  14. Vescovo G, Serafini F, Facchin L, Tenderini P, Carraro U, Dalla Libera L, Catani C, Ambrosio GB (1996) Specific changes in skeletal muscle myosin heavy chain composition in cardiac failure: differences compared with disuse atrophy as assessed on microbiopsies by high resolution electrophoresis. Heart 76:337–343

    PubMed  CAS  Google Scholar 

  15. Simonini A, Long CS, Dudley GA, Yue P, McElhinny J, Massie BM (1996) Heart failure in rats causes changes in skeletal muscle morphology and gene expression that are not explained by reduced activity. Circ Res 79:128–136

    PubMed  CAS  Google Scholar 

  16. Knight DR, Poole DC, Schaffartzik W, Guy HJ, Prediletto R, Hogan MC, Wagner PD (1992) Relationship between body and leg VO2 during maximal cycle ergometry. J Appl Physiol 73:1114–1121

    PubMed  CAS  Google Scholar 

  17. Saltin B, Henriksson J, Nygaard E, Andersen P, Jansson E (1977) Fiber types and metabolic potentials of skeletal muscles in sedentary man and endurance runners. Ann NY Acad Sci 301:3–29

    PubMed  CAS  Google Scholar 

  18. Wilson JR, Martin JL, Schwartz D, Ferraro N (1984) Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation 69:1079–1087

    PubMed  CAS  Google Scholar 

  19. Sullivan MJ, Knight JD, Higginbotham MB, Cobb FR (1989) Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 80:769–781

    PubMed  CAS  Google Scholar 

  20. LeJemtel TH, Maskin CS, Lucido D, Chadwick BJ (1986) Failure to augment maximal limb blood flow in response to one-leg versus two-leg exercise in patients with severe heart failure. Circulation 74:245–251

    PubMed  CAS  Google Scholar 

  21. Zelis R, Longhurst J, Capone RJ, Mason DT (1974) A comparison of regional blood flow and oxygen utilization during dynamic forearm exercise in normal subjects and patients with congestive heart failure. Circulation 50:137–143

    PubMed  CAS  Google Scholar 

  22. Sullivan MJ, Cobb FR (1991) Dynamic regulation of leg vasomotor tone in patients with chronic heart failure. J Appl Physiol 71:1070–1075

    PubMed  CAS  Google Scholar 

  23. Zelis R, Mason DT, Braunwald E (1968) A comparison of the effects of vasodilator stimuli on peripheral resistance vessels in normal subjects and in patients with congestive heart failure. J Clin Invest 47:960–970

    PubMed  CAS  Google Scholar 

  24. Hornig B, Maier V, Drexler H (1996) Physical training improves endothelial function in patients with chronic heart failure. Circulation 93:210–214

    PubMed  CAS  Google Scholar 

  25. Hambrecht R, Niebauer J, Fiehn E, Kalberer B, Offner B, Hauer K, Riede U, Schlierf G, Kubler W, Schuler G (1995) Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. J Am Coll Cardiol 25:1239–1249

    PubMed  CAS  Google Scholar 

  26. Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 250:H1145–H1149

    PubMed  CAS  Google Scholar 

  27. Katz SD, Biasucci L, Sabba C, Strom JA, Jondeau G, Galvao M, Solomon S, Nikolic SD, Forman R, LeJemtel TH (1992) Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol 19:918–925

    PubMed  CAS  Google Scholar 

  28. Kubo SH, Rector TS, Bank AJ, Williams RE, Heifetz SM (1991) Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation 84:1589–1596

    PubMed  CAS  Google Scholar 

  29. Katz SD (1995) The role of endothelium-derived vasoactive substances in the pathophysiology of exercise intolerance in patients with congestive heart failure. Prog Cardiovasc Dis 38:23–50

    PubMed  CAS  Google Scholar 

  30. Drexler H, Hornig B (1999) Endothelial dysfunction in human disease. J Mol Cell Cardiol 31:51–60

    PubMed  CAS  Google Scholar 

  31. Kiowski W, Luscher TF, Linder L, Buhler FR (1991) Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation 83:469–475

    PubMed  CAS  Google Scholar 

  32. Haynes WG, Webb DJ (1998) Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 16:1081–1098

    PubMed  CAS  Google Scholar 

  33. Sullivan MJ, Green HJ, Cobb FR (1990) Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure. Circulation 81:518–527

    PubMed  CAS  Google Scholar 

  34. Weber KT, Janicki JS (1985) Lactate production during maximal and submaximal exercise in patients with chronic heart failure. J Am Coll Cardiol 6:717–724

    PubMed  CAS  Google Scholar 

  35. Jeserich M, Munzel T, Pape L, Fischer C, Drexler H, Just H (1995) Absence of vascular tolerance in conductance vessels after 48 hours of intravenous nitroglycerin in patients with coronary artery disease. J Am Coll Cardiol 26:50–56

    PubMed  CAS  Google Scholar 

  36. Drexler H, Banhardt U, Meinertz T, Wollschlager H, Lehmann M, Just H (1989) Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. A double-blind, placebo-controlled trial. Circulation 79:491–502

    PubMed  CAS  Google Scholar 

  37. Duscha BD, Kraus WE, Keteyian SJ, Sullivan MJ, Green HJ, Schachat FH, Pippen AM, Brawner CA, Blank JM, Annex BH (1999) 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 33:1956–1963

    PubMed  CAS  Google Scholar 

  38. Magnusson G, Kaijser L, Rong H, Isberg B, Sylven C, Saltin B (1996) Exercise capacity in heart failure patients: relative importance of heart and skeletal muscle. Clin Physiol 16:183–195

    PubMed  CAS  Google Scholar 

  39. Williams AD, Selig S, Hare DL, Hayes A, Krum H, Patterson J, Geerling RH, Toia D, Carey MF (2004) Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity. J Card Fail 10:141–148

    PubMed  CAS  Google Scholar 

  40. Drexler H, Riede U, Munzel T, Konig H, Funke E, Just H (1992) Alterations of skeletal muscle in chronic heart failure. Circulation 85:1751–1759

    PubMed  CAS  Google Scholar 

  41. Schaufelberger M, Eriksson BO, Grimby G, Held P, Swedberg K (1995) Skeletal muscle fiber composition and capillarization in patients with chronic heart failure: relation to exercise capacity and central hemodynamics. J Card Fail 1:267–272

    PubMed  CAS  Google Scholar 

  42. Mancini DM, Coyle E, Coggan A, Beltz J, Ferraro N, Montain S, Wilson JR (1989) Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. Circulation 80:1338–1346

    PubMed  CAS  Google Scholar 

  43. Koike A, Wasserman K, Taniguchi K, Hiroe M, Marumo F (1994) Critical capillary oxygen partial pressure and lactate threshold in patients with cardiovascular disease. J Am Coll Cardiol 23:1644–1650

    PubMed  CAS  Google Scholar 

  44. Andersen P, Saltin B (1985) Maximal perfusion of skeletal muscle in man. J Physiol 366:233–249

    PubMed  CAS  Google Scholar 

  45. Saltin B, Kiens B, Savard G, Pedersen PK (1986) Role of hemoglobin and capillarization for oxygen delivery and extraction in muscular exercise. Acta Physiol Scand Suppl 556:21–32

    PubMed  CAS  Google Scholar 

  46. Annex BH, Torgan CE, Lin P, Taylor DA, Thompson MA, Peters KG, Kraus WE (1998) Induction and maintenance of increased VEGF protein by chronic motor nerve stimulation in skeletal muscle. Am J Physiol 274:H860–H867

    PubMed  CAS  Google Scholar 

  47. Folkman J (1995) Seminars in medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 333:1757–1763

    PubMed  CAS  Google Scholar 

  48. Gustafsson T, Bodin K, Sylven C, Gordon A, Tyni-Lenne R, Jansson E (2001) Increased expression of VEGF following exercise training in patients with heart failure. Eur J Clin Invest 31:362–366

    PubMed  CAS  Google Scholar 

  49. Namiki A, Brogi E, Kearney M, Kim EA, Wu T, Couffinhal T, Varticovski L, Isner JM (1995) Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J Biol Chem 270:31189–31195

    PubMed  CAS  Google Scholar 

  50. Houston ME, Bentzen H, Larsen H (1979) Interrelationships between skeletal muscle adaptations and performance as studied by detraining and retraining. Acta Physiol Scand 105:163–170

    Article  PubMed  CAS  Google Scholar 

  51. Hoppeler H, Luthi P, Claassen H, Weibel ER, Howald H (1973) The ultrastructure of the normal human skeletal muscle. A morphometric analysis on untrained men, women and well-trained orienteers. Pflugers Arch 344:217–232

    PubMed  CAS  Google Scholar 

  52. Kiessling KH, Pilstrom L, Bylund AC, Saltin B, Piehl K (1974) Enzyme activities and morphometry in skeletal muscle of middle-aged men after training. Scand J Clin Lab Invest 33:63–69

    PubMed  CAS  Google Scholar 

  53. Kemp GJ, Thompson CH, Stratton JR, Brunotte F, Conway M, Adamopoulos S, Arnolda L, Radda GK, Rajagopalan B (1996) Abnormalities in exercising skeletal muscle in congestive heart failure can be explained in terms of decreased mitochondrial ATP synthesis, reduced metabolic efficiency, and increased glycogenolysis. Heart 76:35–41

    PubMed  CAS  Google Scholar 

  54. Okita K, Yonezawa K, Nishijima H, Hanada A, Nagai T, Murakami T, Kitabatake A (2001) Muscle high-energy metabolites and metabolic capacity in patients with heart failure. Med Sci Sports Exerc 33:442–448

    PubMed  CAS  Google Scholar 

  55. Chati Z, Zannad F, Robin-Lherbier B, Escanye JM, Jeandel C, Robert J, Aliot E (1994) Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study. Am Heart J 128:781–792

    PubMed  CAS  Google Scholar 

  56. Mancini DM, Wilson JR, Bolinger L, Li H, Kendrick K, Chance B, Leigh JS (1994) In vivo magnetic resonance spectroscopy measurement of deoxymyoglobin during exercise in patients with heart failure. Demonstration of abnormal muscle metabolism despite adequate oxygenation. Circulation 90:500–508

    PubMed  CAS  Google Scholar 

  57. Toussaint JF, Koelling TM, Schmidt CJ, Kwong KK, LaRaia PJ, Kantor HL (1998) Local relation between oxidative metabolism and perfusion in leg muscles of patients with heart failure studied by magnetic resonance imaging and spectroscopy. J Heart Lung Transplant 17:892–900

    PubMed  CAS  Google Scholar 

  58. Ohtsubo M, Yonezawa K, Nishijima H, Okita K, Hanada A, Kohya T, Murakami T, Kitabatake A (1997) Metabolic abnormality of calf skeletal muscle is improved by localised muscle training without changes in blood flow in chronic heart failure. Heart 78:437–443

    PubMed  CAS  Google Scholar 

  59. Adamopoulos S, Coats AJ, Brunotte F, Arnolda L, Meyer T, Thompson CH, Dunn JF, Stratton J, Kemp GJ, Radda GK et al (1993) Physical training improves skeletal muscle metabolism in patients with chronic heart failure. J Am Coll Cardiol 21:1101–1106

    Article  PubMed  CAS  Google Scholar 

  60. Larsen AI, Lindal S, Aukrust P, Toft I, Aarsland T, Dickstein K (2002) Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity. Int J Cardiol 83:25–32

    PubMed  Google Scholar 

  61. Vescovo G, Serafini F, Dalla Libera L, Leprotti C, Facchin L, Tenderini P, Ambrosio GB (1998) Skeletal muscle myosin heavy chains in heart failure: correlation between magnitude of the isozyme shift, exercise capacity, and gas exchange measurements. Am Heart J 135:130–137

    PubMed  CAS  Google Scholar 

  62. Sullivan MJ, Duscha BD, Klitgaard H, Kraus WE, Cobb FR, Saltin B (1997) Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure. Med Sci Sports Exerc 29:860–866

    PubMed  CAS  Google Scholar 

  63. Schaufelberger M, Andersson G, Eriksson BO, Grimby G, Held P, Swedberg K (1996) Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril. Eur Heart J 17:1678–1685

    PubMed  CAS  Google Scholar 

  64. Ralston MA, Merola AJ, Leier CV (1991) Depressed aerobic enzyme activity of skeletal muscle in severe chronic heart failure. J Lab Clin Med 117:370–372

    PubMed  CAS  Google Scholar 

  65. Sullivan MJ, Green HJ, Cobb FR (1991) Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity. Circulation 84:1597–1607

    PubMed  CAS  Google Scholar 

  66. Pu CT, Johnson MT, Forman DE, Hausdorff JM, Roubenoff R, Foldvari M, Fielding RA, Singh MA (2001) Randomized trial of progressive resistance training to counteract the myopathy of chronic heart failure. J Appl Physiol 90:2341–2350

    PubMed  CAS  Google Scholar 

  67. Saltin B, Rowell LB (1980) Functional adaptations to physical activity and inactivity. Fed Proc 39:1506–1513

    PubMed  CAS  Google Scholar 

  68. Holloszy JO, Coyle EF (1984) Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56:831–838

    PubMed  CAS  Google Scholar 

  69. Adams V, Jiang H, Yu J, Mobius-Winkler S, Fiehn E, Linke A, Weigl C, Schuler G, Hambrecht R (1999) Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. J Am Coll Cardiol 33:959–965

    PubMed  CAS  Google Scholar 

  70. Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, Poole-Wilson PA, Coats AJ (1997) Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation 96:526–534

    PubMed  CAS  Google Scholar 

  71. Levine B, Kalman J, Mayer L, Fillit HM, Packer M (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323:236–241

    Article  PubMed  CAS  Google Scholar 

  72. Adams V, Nehrhoff B, Spate U, Linke A, Schulze PC, Baur A, Gielen S, Hambrecht R, Schuler G (2002) Induction of iNOS expression in skeletal muscle by IL-1beta and NFkappaB activation: an in vitro and in vivo study. Cardiovasc Res 54:95–104

    PubMed  CAS  Google Scholar 

  73. Oral H, Dorn GW 2nd, Mann DL (1997) Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte. J Biol Chem 272:4836–4842

    PubMed  CAS  Google Scholar 

  74. Adams V, Spate U, Krankel N, Schulze PC, Linke A, Schuler G, Hambrecht R (2003) Nuclear factor-kappa B activation in skeletal muscle of patients with chronic heart failure: correlation with the expression of inducible nitric oxide synthase. Eur J Cardiovasc Prev Rehabil 10:273–277

    PubMed  Google Scholar 

  75. Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119:285–298

    PubMed  CAS  Google Scholar 

  76. Gielen S, Adams V, Linke A, Erbs S, Mobius-Winkler S, Schubert A, Schuler G, Hambrecht R (2005) Exercise training in chronic heart failure: correlation between reduced local inflammation and improved oxidative capacity in the skeletal muscle. Eur J Cardiovasc Prev Rehabil 12:393–400

    PubMed  Google Scholar 

  77. Ng EH, Rock CS, Lazarus DD, Stiaino-Coico L, Moldawer LL, Lowry SF (1992) Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia. Am J Physiol 262:R426–R431

    PubMed  CAS  Google Scholar 

  78. Douglas RG, Gluckman PD, Breier BH, McCall JL, Parry B, Shaw JH (1991) Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs. Am J Physiol 261:E606–E612

    PubMed  CAS  Google Scholar 

  79. Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, Poole-Wilson PA, Coats AJ (1997) Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation 96:526–534

    PubMed  CAS  Google Scholar 

  80. Levine B, Kalman J, Mayer L, Fillit HM, Packer MP (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323:236–241

    Article  PubMed  CAS  Google Scholar 

  81. Niebauer J, Pflaum CD, Clark AL, Strasburger CJ, Hooper J, Poole-Wilson PA, Coats AJ, Anker SD (1998) Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. J Am Coll Cardiol 32:393–397

    PubMed  CAS  Google Scholar 

  82. Hambrecht R, Schulze PC, Gielen S, Linke A, Mobius-Winkler S, Yu J, Kratzsch JJ, Baldauf G, Busse MW, Schubert A, Adams V, Schuler G (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

    PubMed  CAS  Google Scholar 

  83. Schulze PC, Gielen S, Adams V, Linke A, Mobius-Winkler S, Erbs S, Kratzsch J, Hambrecht R, Schuler G (2003) Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulin-like growth factor-I in chronic heart failure. Basic Res Cardiol 98:267–274

    PubMed  CAS  Google Scholar 

  84. Vescovo G, Ambrosio GB, Dalla Libera L (2001) Apoptosis and changes in contractile protein pattern in the skeletal muscle in heart failure. Acta Physiol Scand 171:305–310

    PubMed  CAS  Google Scholar 

  85. Dalla LL, Sabbadini R, Renken C, Ravara B, Sandri M, Betto R, Angelini A, Vescovo G (2001) Apoptosis in the skeletal muscle of rats with heart failure is associated with increased serum levels of TNF-alpha and sphingosine. J Mol Cell Cardiol 33:1871–1878

    Google Scholar 

  86. Gosselin LE, Barkley JE, Spencer MJ, McCormick KM, Farkas GA (2003) Ventilatory dysfunction in mdx mice: impact of tumor necrosis factor-alpha deletion. Muscle Nerve 28:336–343

    PubMed  CAS  Google Scholar 

  87. Ferrari R, Bachetti T, Agnoletti L, Comini L, Curello S (1998) Endothelial function and dysfunction in heart failure. Eur Heart J 19(Suppl G):G41–G47

    PubMed  CAS  Google Scholar 

  88. Agnoletti L, Curello S, Bachetti T, Malacarne F, Gaia G, Comini L, Volterrani M, Bonetti P, Parrinello G, Cadei M, Grigolato PG, Ferrari R (1999) Serum from patients with severe heart failure downregulates eNOS and is proapoptotic: role of tumor necrosis factor-alpha. Circulation 100:1983–1991

    PubMed  CAS  Google Scholar 

  89. Powers SK, Criswell D, Lawler J, Martin D, Lieu FK, Ji LL, Herb RA (1993) Rigorous exercise training increases superoxide dismutase activity in ventricular myocardium. Am J Physiol 265:H2094–H2098

    PubMed  CAS  Google Scholar 

  90. McMurray J, McLay J, Chopra M, Bridges A, Belch JJ (1990) Evidence for enhanced free radical activity in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 65:1261–1262

    PubMed  CAS  Google Scholar 

  91. Mancini DM, Walter G, Reichek N, Lenkinski R, McCully KK, Mullen JL, Wilson JR (1992) Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation 85:1364–1373

    PubMed  CAS  Google Scholar 

  92. Minotti JR, Pillay P, Oka R, Wells L, Christoph I, Massie BM (1993) Skeletal muscle size: relationship to muscle function in heart failure. J Appl Physiol 75:373–381

    PubMed  CAS  Google Scholar 

  93. Massie BM, Simonini A, Sahgal P, Wells L, Dudley GA (1996) Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol 27:140–145

    PubMed  CAS  Google Scholar 

  94. Harrington D, Anker SD, Chua TP, Webb-Peploe KM, Ponikowski PP, Poole-Wilson PA, Coats AJ (1997) Skeletal muscle function and its relation to exercise tolerance in chronic heart failure. J Am Coll Cardiol 30:1758–1764

    PubMed  CAS  Google Scholar 

  95. Buller NP, Jones D, Poole-Wilson PA (1991) Direct measurement of skeletal muscle fatigue in patients with chronic heart failure. Br Heart J 65:20–24

    PubMed  CAS  Google Scholar 

  96. Lang CC, Chomsky DB, Rayos G, Yeoh TK, Wilson JR (1997) Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure. J Appl Physiol 82:257–261

    PubMed  CAS  Google Scholar 

  97. Lipkin DP, Jones DA, Round JM, Poole-Wilson PA (1988) Abnormalities of skeletal muscle in patients with chronic heart failure. Int J Cardiol 18:187–195

    PubMed  CAS  Google Scholar 

  98. Libera LD, Vescovo G (2004) Muscle wastage in chronic heart failure, between apoptosis, catabolism and altered anabolism: a chimaeric view of inflammation? Curr Opin Clin Nutr Metab Care 7:435–441

    PubMed  Google Scholar 

  99. Vescovo G, Volterrani M, Zennaro R, Sandri M, Ceconi C, Lorusso R, Ferrari R, Ambrosio GB, Dalla Libera L (2000) Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes. Heart 84:431–437

    PubMed  CAS  Google Scholar 

  100. Adams V, Yu J, Mobius-Winkler S, Linke A, Weigl C, Hilbrich L, Schuler G, Hambrecht R (1997) Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure. Biochem Mol Med 61:152–160

    PubMed  CAS  Google Scholar 

  101. Messmer UK, Brune B (1996) Nitric oxide (NO) in apoptotic versus necrotic RAW 264.7 macrophage cell death: the role of NO-donor exposure, NAD+ content, and p53 accumulation. Arch Biochem Biophys 327:1–10

    PubMed  CAS  Google Scholar 

  102. Schulze PC, Spate U (2005) Insulin-like growth factor-1 and muscle wasting in chronic heart failure. Int J Biochem Cell Biol 37:2023–2035

    PubMed  CAS  Google Scholar 

  103. Song YH, Li Y, Du J, Mitch WE, Rosenthal N, Delafontaine P (2005) Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting. J Clin Invest 115:451–458

    PubMed  CAS  Google Scholar 

  104. Liu Z, Miers WR, Wei L, Barrett EJ (2000) The ubiquitin-proteasome proteolytic pathway in heart vs skeletal muscle: effects of acute diabetes. Biochem Biophys Res Commun 276:1255–1260

    PubMed  CAS  Google Scholar 

  105. Costelli P, Tullio RD, Baccino FM, Melloni E (2001) Activation of Ca(2+)-dependent proteolysis in skeletal muscle and heart in cancer cachexia. Br J Cancer 84:946–950

    PubMed  CAS  Google Scholar 

  106. Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH, Goldberg AL, Spiegelman BM (2006) PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci USA 103:16260–16265

    PubMed  CAS  Google Scholar 

  107. Jagoe RT, Lecker SH, Gomes M, Goldberg AL (2002) Patterns of gene expression in atrophying skeletal muscles: response to food deprivation. Faseb J 16:1697–1712

    PubMed  CAS  Google Scholar 

  108. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA 98:14440–14445

    PubMed  CAS  Google Scholar 

  109. Tiao G, Fagan JM, Samuels N, James JH, Hudson K, Lieberman M, Fischer JE, Hasselgren PO (1994) Sepsis stimulates nonlysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. J Clin Invest 94:2255–2264

    Article  PubMed  CAS  Google Scholar 

  110. Schulze PC, Fang J, Kassik KA, Gannon J, Cupesi M, MacGillivray C, Lee RT, Rosenthal N (2005) Transgenic overexpression of locally acting insulin-like growth factor-1 inhibits ubiquitin-mediated muscle atrophy in chronic left-ventricular dysfunction. Circ Res 97:418–426

    PubMed  CAS  Google Scholar 

  111. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708

    PubMed  CAS  Google Scholar 

  112. Spate U, Schulze PC (2004) Proinflammatory cytokines and skeletal muscle. Curr Opin Clin Nutr Metab Care 7:265–269

    PubMed  Google Scholar 

  113. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M, Yancopoulos GD, Glass DJ (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 14:395–403

    PubMed  CAS  Google Scholar 

  114. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117:399–412

    PubMed  CAS  Google Scholar 

  115. Dalla Libera L, Ravara B, Volterrani M, Gobbo V, Della Barbera M, Angelini A, Betto DD, Germinario E, Vescovo G (2004) Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure. Am J Physiol Cell Physiol 286:C138–C144

    PubMed  CAS  Google Scholar 

  116. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, Price SR, Mitch WE, Goldberg AL (2004) Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. Faseb J 18:39–51

    PubMed  CAS  Google Scholar 

  117. Furuyama T, Nakazawa T, Nakano I, Mori N (2000) Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues. Biochem J 349:629–634

    PubMed  CAS  Google Scholar 

  118. Tyni-Lenne R, Gordon A, Jansson E, Bermann G, Sylven C (1997) Skeletal muscle endurance training improves peripheral oxidative capacity, exercise tolerance, and health-related quality of life in women with chronic congestive heart failure secondary to either ischemic cardiomyopathy or idiopathic dilated cardiomyopathy. Am J Cardiol 80:1025–1029

    PubMed  CAS  Google Scholar 

  119. Tyni-Lenne R, Gordon A, Europe E, Jansson E, Sylven C (1998) Exercise-based rehabilitation improves skeletal muscle capacity, exercise tolerance, and quality of life in both women and men with chronic heart failure. J Card Fail 4:9–17

    PubMed  CAS  Google Scholar 

  120. Tyni-Lenne R, Jansson E, Sylven C (1999) Female-related skeletal muscle phenotype in patients with moderate chronic heart failure before and after dynamic exercise training. Cardiovasc Res 42:99–103

    PubMed  CAS  Google Scholar 

  121. Duscha BD, Annex BH, Keteyian SJ, Green HJ, Sullivan MJ, Samsa GP, Brawner CA, Schachat FH, Kraus WE (2001) Differences in skeletal muscle between men and women with chronic heart failure. J Appl Physiol 90:280–286

    PubMed  CAS  Google Scholar 

  122. Keteyian SJ, Duscha BD, Brawner CA, Green HJ, Marks CR, Schachat FH, Annex BH, Kraus WE (2003) Differential effects of exercise training in men and women with chronic heart failure. Am Heart J 145:912–918

    PubMed  Google Scholar 

  123. Hambrecht R, Fiehn E, Yu J, Niebauer J, Weigl C, Hilbrich L, Adams V, Riede U, Schuler G (1997) Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure. J Am Coll Cardiol 29:1067–1073

    PubMed  CAS  Google Scholar 

  124. Belardinelli R, Georgiou D, Scocco V, Barstow TJ, Purcaro A (1995) Low intensity exercise training in patients with chronic heart failure. J Am Coll Cardiol 26:975–982

    PubMed  CAS  Google Scholar 

  125. Magnusson G, Gordon A, Kaijser L, Sylven C, Isberg B, Karpakka J, Saltin B (1996) High intensity knee extensor training, in patients with chronic heart failure. Major skeletal muscle improvement. Eur Heart J 17:1048–1055

    PubMed  CAS  Google Scholar 

  126. Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, Kempf W, Schubert A, Schuler G, Hambrecht R (2003) Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 42:861–868

    PubMed  CAS  Google Scholar 

  127. Gordon A, Tyni-Lenne R, Jansson E, Kaijser L, Theodorsson-Norheim E, Sylven C (1997) Improved ventilation and decreased sympathetic stress in chronic heart failure patients following local endurance training with leg muscles. J Card Fail 3:3–12

    PubMed  CAS  Google Scholar 

  128. Hambrecht R, Fiehn E, Weigl C, Gielen S, Hamann C, Kaiser R, Yu J, Adams V, Niebauer J, Schuler G (1998) Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98:2709–2715

    PubMed  CAS  Google Scholar 

  129. Adamopoulos S, Parissis J, Karatzas D, Kroupis C, Georgiadis M, Karavolias G, Paraskevaidis J, Koniavitou K, Coats AJ, Kremastinos DT (2002) Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure. J Am Coll Cardiol 39:653–663

    PubMed  CAS  Google Scholar 

  130. Varin R, Mulder P, Richard V, Tamion F, Devaux C, Henry JP, Lallemand F, Lerebours G, Thuillez C (1999) Exercise improves flow-mediated vasodilatation of skeletal muscle arteries in rats with chronic heart failure. Role of nitric oxide, prostanoids, and oxidant stress. Circulation 99:2951–2957

    PubMed  CAS  Google Scholar 

  131. Green DJ, Maiorana A, O’Driscoll G, Taylor R (2004) Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 561:1–25

    PubMed  CAS  Google Scholar 

  132. McKoy G, Ashley W, Mander J, Yang SY, Williams N, Russell B, Goldspink G (1999) Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. J Physiol 516.2:583–592

    Google Scholar 

  133. Eliakim A, Moromisato M, Moromisato D, Brasel JA, Roberts C, Cooper DM (1997) Increase in muscle IGF-I protein but not IGF-I mRNA after 5 days of endurance training in young rats. Am J Physiol 273:R1557–R1561

    PubMed  CAS  Google Scholar 

  134. Schulze PC, Linke A, Gielen S, Moebius-Winkler S, Schoene N, Erbs S, Adams V, Hambrecht R (2001) Effects of exercise training on the local expression of insulin-like growth factor-I in the skeletal muscle of patients with chronic heart failure. Eur Heart J 22:503

    Google Scholar 

  135. Schulze PC, Gielen S, Schuler G, Hambrecht R (2002) Chronic heart failure and skeletal muscle catabolism: effects of exercise training. Int J Cardiol 85:141–149

    PubMed  Google Scholar 

  136. Hellsten Y, Hansson HA, Johnson L, Frandsen U, Sjodin B (1996) Increased expression of xanthine oxidase and insulin-like growth factor I (IGF-I) immunoreactivity in skeletal muscle after strenuous exercise in humans. Acta Physiol Scand 157:191–197

    PubMed  CAS  Google Scholar 

  137. Singh MA, Ding W, Manfredi TJ, Solares GS, O’Neill EF, Clements KM, Ryan ND, Kehayias JJ, Fielding RA, Evans WJ (1999) Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders. Am J Physiol 277:E135–E143

    PubMed  CAS  Google Scholar 

  138. Baldwin KM, Haddad F (2001) Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. J Appl Physiol 90:345–357

    PubMed  CAS  Google Scholar 

  139. Forman D, Hunt B, Santoro C, Bairos L, Levesque S, Roubenoff R, Cosmas A, Manfredi T (2000) Progressive resistance training safely improves aerobic metabolism clinical function, and underlying mitochodrial morphometry in elderly heart failure patients. Circulation 102:II:678 (3280)

    Google Scholar 

  140. Grosse T, Kreulich K, Naegele H (2001) Peripheral muscular strength training in patients with severe heart failure. Dtsch Z Sportmed 52:11–14

    Google Scholar 

  141. Williams AD, Carey MF, Selig S, Hayes A, Krum H, Patterson J, Toia D, Hare DL (2007) Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate—a randomized controlled trial. J Card Fail 13:79–85

    PubMed  CAS  Google Scholar 

  142. Hickson RC, Rosenkoetter MA, Brown MM (1980) Strength training effects on aerobic power and short-term endurance. Med Sci Sports Exerc 12:336–339

    PubMed  CAS  Google Scholar 

  143. Hare DL, Ryan TM, Selig SE, Pellizzer AM, Wrigley TV, Krum H (1999) Resistance exercise training increases muscle strength, endurance, and blood flow in patients with chronic heart failure. Am J Cardiol 83:1674–1677, A7

    PubMed  CAS  Google Scholar 

  144. Maiorana A, O’Driscoll G, Cheetham C, Collis J, Goodman C, Rankin S, Taylor R, Green D (2000) Combined aerobic and resistance exercise training improves functional capacity and strength in CHF. J Appl Physiol 88:1565–1570

    PubMed  CAS  Google Scholar 

  145. Delagardelle C, Feiereisen P, Krecke R, Essamri B, Beissel J (1999) Objective effects of a 6 months’ endurance and strength training program in outpatients with congestive heart failure. Med Sci Sports Exerc 31:1102–1107

    PubMed  CAS  Google Scholar 

  146. Selig SE, Carey MF, Menzies DG, Patterson J, Geerling RH, Williams AD, Bamroongsuk V, Toia D, Krum H, Hare DL (2004) Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow. J Card Fail 10:21–30

    PubMed  Google Scholar 

  147. Delagardelle C, Feiereisen P, Autier P, Shita R, Krecke R, Beissel J (2002) Strength/endurance training versus endurance training in congestive heart failure. Med Sci Sports Exerc 34:1868–1872

    PubMed  Google Scholar 

  148. Santoro C, Cosmas A, Forman D, Morghan A, Bairos L, Levesque S, Roubenoff R, Hennessey J, Lamont L, Manfredi T (2002) Exercise training alters skeletal muscle mitochondrial morphometry in heart failure patients. J Cardiovasc Risk 9:377–381

    PubMed  Google Scholar 

  149. Walker KS, Kambadur R, Sharma M, Smith HK (2004) Resistance training alters plasma myostatin but not IGF-1 in healthy men. Med Sci Sports Exerc 36:787–793

    PubMed  CAS  Google Scholar 

  150. Adamo ML, Farrar RP (2006) Resistance training, and IGF involvement in the maintenance of muscle mass during the aging process. Ageing Res Rev 5:310–331

    PubMed  CAS  Google Scholar 

  151. Pollock ML, Franklin BA, Balady GJ, Chaitman BL, Fleg JL, Fletcher B, Limacher M, Pina IL, Stein RA, Williams M, Bazzarre T (2000) AHA Science Advisory. Resistance exercise in individuals with and without cardiovascular disease: benefits, rationale, safety, and prescription: an advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association; Position paper endorsed by the American College of Sports Medicine. Circulation 101:828–833

    PubMed  CAS  Google Scholar 

  152. Harjola VP, Kiilavuori K, Virkamaki A (2006) The effect of moderate exercise training on skeletal muscle myosin heavy chain distribution in chronic heart failure. Int J Cardiol 109:335–338

    PubMed  Google Scholar 

  153. Hambrecht R, Schulze PC, Gielen S, Linke A, Mobius-Winkler S, Erbs S, Kratzsch J, Schubert A, Adams V, Schuler G (2005) Effects of exercise training on insulin-like growth factor-I expression in the skeletal muscle of non-cachectic patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 12:401–406

    PubMed  Google Scholar 

  154. Kiilavuori K, Naveri H, Salmi T, Harkonen M (2000) The effect of physical training on skeletal muscle in patients with chronic heart failure. Eur J Heart Fail 2:53–63

    PubMed  CAS  Google Scholar 

  155. Scarpelli M, Belardinelli R, Tulli D, Provinciali L (1999) Quantitative analysis of changes occurring in muscle vastus lateralis in patients with heart failure after low-intensity training. Anal Quant Cytol Histol 21:374–380

    PubMed  CAS  Google Scholar 

  156. Gordon A, Tyni-Lenne R, Persson H, Kaijser L, Hultman E, Sylven C (1996) Markedly improved skeletal muscle function with local muscle training in patients with chronic heart failure. Clin Cardiol 19:568–574

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Duke University Medical Center, Box 3022, Durham, NC, 27710, USA

    Brian D. Duscha & Jennifer L. Robbins

  2. Division of Cardiology, New York Presbyterian Hospital, Columbia University Medical Center, 622 West 168th Street, PH 3-347, New York, NY, 10032, USA

    P. Christian Schulze

  3. Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Daniel E. Forman

  4. Veteran’s Administration Medical Center (VAMC) of Boston, Boston, MA, USA

    Daniel E. Forman

  5. Harvard Medical School, Boston, MA, USA

    Daniel E. Forman

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  1. Brian D. Duscha
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Correspondence to Daniel E. Forman.

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Duscha, B.D., Schulze, P.C., Robbins, J.L. et al. Implications of chronic heart failure on peripheral vasculature and skeletal muscle before and after exercise training. Heart Fail Rev 13, 21–37 (2008). https://doi.org/10.1007/s10741-007-9056-8

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