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Muscle Reflex Control of Sympathetic Nerve Activity in Heart Failure: The Role of Exercise Conditioning

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Abstract

Muscle reflex control of sympathetic nerve activity has been an area of considerable investigation. During exercise, the capacity of the peripheral vasculature to dilate far exceeds the maximal attainable levels of cardiac output. The activation of sympathetic nervous system and engagement of the myogenic reflex serve as the controlling influence between the heart and the muscle vasculature to maintain blood pressure (BP). Two basic theories of neural control have evolved. The first termed “central command”, suggests that a volitional signal emanating from central motor areas leads to increased sympathetic activation during exercise. According to the second theory the stimulation of mechanical and chemical afferents in exercising muscle lead to engagement of the “exercise pressor reflex”. Some earlier studies suggested that group III muscle afferent fibers are predominantly mechanically sensitive whereas unmyelinated group IV muscle afferents respond to chemical stimuli. In recent years new evidence is emerging which challenges the concept of functional differentiation of muscle afferents as well as the classic description of muscle “mechano” and “metabo” receptors. Studies measuring concentrations of interstitial substances during exercise suggest that K+ and phosphate, but not H+ and lactate, may be important muscle afferent stimulants. The role of adenosine as a muscle afferent stimulant remains an area of debate.

There is strong evidence that sympathetic vasoconstriction due to muscle reflex engagement plays an important role in restricting blood flow to the exercising muscle. In heart failure (HF), exercise leads to premature fatigue and accumulation of muscle metabolites resulting in a greater degree of muscle reflex engagement and in the process further decreasing the muscle blood flow. Conditioning leads to an increased ability of the muscle to maintain aerobic metabolism, lowerinterstitial accumulation of metabolites, less muscle reflex engagement and a smaller sympathetic response. Beneficial effects of physical conditioning may be mediated by a direct reduction of muscle metaboreflex activity or via reduction of metabolic signals activating these receptors.

In this review, we will discuss concepts of flow and reflex engagement in normal human subjects and then contrast these findings with those seen in heart failure (HF). We will then examine the effects of exercise conditioning on these parameters in normal subjects and those with congestive heart failure (CHF).

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References

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

    Google Scholar 

  2. Armstrong RB, Laughlin MH. Exercise blood flow patterns within and among rat muscles after training.Am J Physiol 1984;246 (Heart Circ. Physiol. 15):H59-H68.

  3. Musch TI, Haidet GC, Ordway GA, Longhurst JC, Mitchell JH. Training effects on regional blood flow response to maximal exercise in foxhounds. J Appl Physiol 1987;62(4):1724–1732.

    Google Scholar 

  4. Laughlin MH, Korthuis RJ, Duncker DJ, Bache RJ. Control of blood flow to cardiac and skeletal muscle during exercise. In Handbook of Physiology, Section 12, Exercise: Regulation and Integration of Multiple Systems, ed. L.B. Rowell and J.T. Shepherd. Chapter 16, pp. 705–769. New York: Oxford University Press, 1996.

    Google Scholar 

  5. Savard GK, Richter EA, Strange S, Kiens B, Christensen NJ, Saltin B. Norepinephrine spillover from skeletal muscle during exercise in humans: role of muscle mass. Am J Physiol 1989;257 (Heart Circ. Physiol. 26):H1812-H1818.

    Google Scholar 

  6. Leuenberger U, Sinoway L, Gubin S, Gaul L, Davis D, Zelis R. Effects of exercise intensity and duration on norepinephrine spillover and clearance in humans. J Appl Physiol 1993;75(2):668–674.

    Google Scholar 

  7. Mark AL, Victor RG, Nerhed C, Wallin BG. Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. Circ Res 1985;57:461–469.

    Google Scholar 

  8. Mitchell JH, Payne FC, Saltin B, Schibye B. The role of muscle mass in the cardiovascular response to static contractions. J Physiol (London) 1980;309:45–54.

    Google Scholar 

  9. Seals DR. Influence of muscle mass on sympathetic neural activation during isometric exercise. J Appl Physiol 1989;67(5):1801–1806.

    Google Scholar 

  10. Lind AR, Taylor SH, Humphreys PW, Kennelly BM, Donald KW. The circulatory effects of sustained voluntary muscle contraction. Clin Sci 1964;27:229–244.

    Google Scholar 

  11. Seals DR, Enoka RM. Sympathetic activation is associated with increases in EMG during fatiguing exercise. J Appl Physiol 1989;66(1):88–95.

    Google Scholar 

  12. Saito M, Mano T, Iwase S. Sympathetic nerve activity related to local fatigue sensation during static contraction. J Appl Physiol 1989;67(3):980–984.

    Google Scholar 

  13. Vanhoutte PM, Verbueren TJ, Webb RC. Local modulation of adrenergic neuroeffector interaction in the blood vessel wall. Physiol Rev 1981;61:151–247.

    Google Scholar 

  14. Remensynder JP, Mitchell JH, Sarnoff SJ. Functional sympatholysis during muscular activity. Observations of influence of carotid sinus on oxygen uptake. Circ Res 1962;11:370–380.

    Google Scholar 

  15. Kurjiaka DT, Segal SS. Interaction between conducted vasodilation and sympathetic nerve activation in arterioles of hamster striated muscle. Circ Res 1995;76:885–891.

    Google Scholar 

  16. McGillivray-Anderson KM, Faber JE. Effect of acidosis on contraction of microvascular smooth muscle by alpha1-and alpha2-adrenoceptors. Implications for neural and metabolic regulation. Circ Res 1990;66:1643–1657.

    Google Scholar 

  17. Hansen J, Thomas GD, Harris SA, Parsons WJ, Victor RG. Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle. J Clin Invest 1996;98(2):584–596.

    Google Scholar 

  18. Vatner SF, Franklin D, Van Citters RL, Braunwald E. Effects of carotid sinus nerve stimulation on blood-flow distribution in conscious dogs at rest and during exercise. Circ Res 1970;27(4):495–503.

    Google Scholar 

  19. Strandell T, Shepherd JT. The effect in humans of increased sympathetic activity on blood flow to active muscles. Acta Med Scand Suppl 1967;472:146–167.

    Google Scholar 

  20. Buckwalter JB, Mueller PJ, Clifford PS. Sympathetic vasoconstriction in active skeletal muscles during dynamic exercise. J Appl Physiol 1997;83(5):1575–1580.

    Google Scholar 

  21. O'Leary DS, Robinson ED, Butler JL. Is active skeletal muscle functionally vasoconstricted during dynamic exercise in conscious dogs? Am J Physiol 1997;272 (Regulatory Integrative Comp. Physiol. 41):R386–R391.

    Google Scholar 

  22. Peterson DF, Armstrong RB, Laughlin MH. Sympathetic neural influences on muscle blood flow in rats during submaximal exercise. J Appl Physiol 1988; 65(1):434–440.

    Google Scholar 

  23. Joyner MJ, Nauss LA, Warner MA, Warner DO. Sympathetic modulation of blood flow and O2 uptake in rhythmically contracting human forearm muscles. Am J Physiol 1992;263 (Heart Circ. Physiol. 32):H1078–H1083.

    Google Scholar 

  24. Donald DE, Rowlands DJ, Ferguson DA. Similarity of blood flow in the normal and the sympathectomized dog hind limb during graded exercise. Circ Res 1970;26:185–199.

    Google Scholar 

  25. Sinoway L, Prophet S. Skeletal muscle metaboreceptor stimulation opposes peak metabolic vasodilation in humans. Circ Res 1990;66(6):1576–1584.

    Google Scholar 

  26. Shoemaker JK, Pandey P, Herr MD, Silber DH, Yang QX, Smith MB, Gray K, Sinoway LI. Augmented sympathetic tone alters muscle metabolism with exercise: lack of evidence for functional sympatholysis. J Appl Physiol 1997;82(6):1932–1938.

    Google Scholar 

  27. Thompson LP, Mohrman DE. Blood flow and oxygen consumption in skeletal muscle during sympathetic stimulation. Am J Physiol 1983;245 (Heart Circ. Physiol. 14):H66–H71.

    Google Scholar 

  28. Flaim SF, Crede W, Beech A, Nellis SN, Zelis R. The effects of norepinephrine on active hyperemia in the canine gracilis muscle. Circ Res 1979;44:660–666.

    Google Scholar 

  29. Rein H, Schneider M. Die lokale Stoffwechseleinschra Ènkung bie reflektorisch-nervoÈser Durchblutungdrosselung. PfluÈ egers Arch 1938;239:464–475.

    Google Scholar 

  30. Rotto DM, Kaufman MP. Effect of metabolic products of muscular contraction on discharge of group III and IV afferents. J Appl Physiol 1988;64(6):2306–2313.

    Google Scholar 

  31. Alam M, Smirk FH. Observations in man upon a blood pressure raising reflex arising from the voluntary muscles. J Physiol (Lond) 1937;89:372–383.

    Google Scholar 

  32. O'Leary DS, Rowell LB, Scher AM. Baroreflex-induced vasoconstriction in active skeletal muscle of conscious dogs. Am J Physiol 1991;260 (Heart Circ. Physiol. 29):H37–H41.

    Google Scholar 

  33. Rowell LB, O'Leary DS. Reflex control of the circulation during exercise: chemoreflexes and mechanore-flexes. J Appl Physiol 1990;69(2):407–418.

    Google Scholar 

  34. Rowell LB, Sheriff DD. Are muscle ``chemoreflexes'' functionally important? News Physiol Sci 1988;3: 250–253.

    Google Scholar 

  35. Victor RG, Bertocci L, Pryor S, Nunnally R. Sympathetic nerve discharge is coupled to muscle cell pH during exercise in humans. J Clin Invest 1988;82: 1301–1305.

    Google Scholar 

  36. Sinoway L, Prophet S, Gorman I, Mosher T, Shenberger J, Dolecki M, Briggs R, Zelis R. Muscle acidosis during static exercise is associated with calf vasoconstriction. J Appl Physiol 1989;66(1):429–436.

    Google Scholar 

  37. Eldridge FL, Millhorn DE, Kiley JP, Waldrop TG. Stimulation by central command of locomotion, respiration and circulation during exercise. Respir Physiol 1985;59:313–337.

    Google Scholar 

  38. Freyschuss U. Cardiovascular adjustment to somatomotor activation. The elicitation of increments in heart rate, aortic pressure and venomotor tone with the initiation of muscle contraction.Acta Physiol Scand 1970;342(Suppl):1–63.

    Google Scholar 

  39. Goodwin GM, McCloskey DI, Mitchell JH. Cardiovascular and respiratory responses to changes in central command during isometric exercise at constant muscle tension. J Physiol (Lond) 1972; 226(1):173–190.

    Google Scholar 

  40. Krogh A, Lindhard J. The regulation of respiration and circulation during the initial stages of muscular work. J Physiol (Lond) 1913-1914;47:112–136.

    Google Scholar 

  41. Victor RG, Pryor SL, Secher NH, Mitchell JH. Effects of partial neuromuscular blockade on sympathetic nerve responses to static exercise in humans.Circ Res 1989;65(2):468–476.

    Google Scholar 

  42. Vissing SF, Scherrer U, Victor RG. Stimulation of skin sympathetic nerve discharge by central command. Differential control of sympathetic outflow to skin and skeletal muscle during static exercise. Circ Res 1991;69(1):228–238.

    Google Scholar 

  43. Victor RG, Secher NH, Lyson T, Mitchell JH. Central command increases muscle sympathetic nerve activity during intense intermittent isometric exercise in humans. Circ Res 1995;76(1):127–131.

    Google Scholar 

  44. Silber DH, Sinoway LI, Leuenberger UA, Amassian VE. Magnetic stimulation of the human motor cortex evokes skin sympathetic nerve activity (SSNA). J Appl Physiol 2000;88:126–134.

    Google Scholar 

  45. Seals DR. Sympathetic neural discharge and vascular resistance during exercise in humans.J Appl Physiol 1989;66(5):2472–2478.

    Google Scholar 

  46. McCloskey DI, Mitchell JH. Reflex cardiovascular and respiratory responses originating in exercising muscle. J Physiol (Lond) 1972;224:173–186.

    Google Scholar 

  47. Victor RG, Rotto DM, Pryor SL, Kaufman MP. Stimulation of renal sympathetic activity by static contraction: evidence for mechanoreceptor-inducedre-flexes from skeletal muscle. Circ Res 1989;64(3): 592–599.

    Google Scholar 

  48. Stebbins CL, Brown B, Levin D, Longhurst JC. Reflex effect of skeletal muscle mechanoreceptor stimulation on the cardiovascular system. J Appl Physiol 1988;65(4):1539–1547.

    Google Scholar 

  49. McMahon SE, McWilliam PN. Changes in R-R interval at the start of muscle contraction in the decerebrate cat. J Physiol (Lond) 1992;447:549–562.

    Google Scholar 

  50. Coote JH, Hilton SM, Pèrez-González JF. The reflex nature of the pressor response to muscular exercise. J Physiol (Lond) 1971;215:789–804.

    Google Scholar 

  51. Stebbins CL, Longhurst JC. Potentiation of the exercise pressor reflex by muscle ischemia. J Appl Physiol 1989;66:1046–1053.

    Google Scholar 

  52. Mizumura K, Kumazawa T. Reflex respiratory response induced by chemical stimulation of muscle afferents. Brain Res 1976;109(2):402–406.

    Google Scholar 

  53. Sato A, Sato Y, Schmidt RF. Heart rate changes reflecting modifications of efferent cardiac sympathetic outflow by cutaneous and muscle afferent volleys. J Auto Nerv Syst 1981;4(3):231–247.

    Google Scholar 

  54. Tibes U. Reflex inputs to the cardiovascular and respiratory centers from dynamically working canine muscles. Circ Res 1977;41(3):332–341.

    Google Scholar 

  55. Waldrop TG, Rybicki KJ, Kaufman MP. Chemical activation of group I and II muscle afferents has no cardiorespiratory effects. J Appl Physiol: Respirat Environ Exercise Physiol 1984;56(5): 1223–1228.

    Google Scholar 

  56. Kaufman MP, Longhurst JC, Rybicki KJ, Wallach JH, Mitchell JH. Effects of static muscular contraction on impulse activity of group III and IV afferents in cats. J Appl Physiol 1983;55(1):105–112.

    Google Scholar 

  57. Kaufman MP, Rybicki KJ, Waldrop TG, Ordway GA. Effect of ischemia on responses of group III and IV Exercise and Heart Failure 97 afferents to contraction. J Appl Physiol 1984;57(3): 644–650.

    Google Scholar 

  58. Sinoway LI, Hill JM, Pickar JG, Kaufman MP. Effects of contraction and lactic acid on the discharge of group III muscle afferents in cats. J Neurophysiol 1993;69(4):1053–1059.

    Google Scholar 

  59. Hayward L, Wesselmann U, Rymer WZ. Effects of muscle fatigue on mechanically sensitive afferents of slow conduction velocity in the cat triceps surae. J Neurophysiol 1991;65(3):360–370.

    Google Scholar 

  60. Adreani CM, Hill JM, Kaufman MP. Responses of group III and IV muscle afferents to dynamic exercise. J Appl Physiol 1997;82(6):1811–1817.

    Google Scholar 

  61. Watt AH, Reid PG, Stephens MR, Routledge PA. Adenosine-induced respiratory stimulation in man depends on site of infusion. Evidence for an action on the carotid body? Br J Clin Pharmacol 1987;23(4):486–490.

    Google Scholar 

  62. Biaggioni I, Onrot J, Hollister AS, Robertson D. Cardiovascular effects of adenosine infusion in man and their modulation by dipyrida. Life Sci 1986; 39(23):2229–2236.

    Google Scholar 

  63. Biaggioni I, Olafsson B, Robertson RM, Hollister AS, Robertson D. Cardiovascular and respiratory effects of adenosine in conscious man: Evidence for chemoreceptor activation. Circ Res 1987;61(6):779–786.

    Google Scholar 

  64. Middlekauff HR, Nitzsche EU, Nguyen AH, Hoh CK, Gibbs GG. Modulation of renal cortical blood flow during static exercise in humans. Circ Res 1997;80: 62–68.

    Google Scholar 

  65. Costa F, Biaggioni I. Adenosine activates afferent fibers in the forearm, producing sympathetic stimulation in humans. Journal of Pharmacology and Experimental Therapeutics 1993;267(3):1369–1374.

    Google Scholar 

  66. Costa F, Biaggioni I. Role of adenosine in the sympathetic activation produced by isometric exercise in humans. J Clin Invest 1994;93(4):1654–1660.

    Google Scholar 

  67. Ettinger S, Gray K, Whisler S, Sinoway L. Dichloroacetate reduces sympathetic nerve responses to static exercise. Am J Physiol 1991;261 (Heart Circ. Physiol. 30):H1653–H1658.

    Google Scholar 

  68. Sinoway LI, Smith MB, Enders B, Leuenberger U, Dzwonczyk T, Gray K, Whisler S, Moore RL. Role of diprotonated phosphate in evoking muscle reflex responses in cats and humans. Am J Physiol 1994;267 (Heart Circ Physiol. 36):H770–H778.

    Google Scholar 

  69. Rybicki KJ, Waldrop TG, Kaufman MP. Increasing gracilis muscle interstitial potassium concentrations stimulate group III and IV afferents. J Appl Physiol 1985;58(3):936–941.

    Google Scholar 

  70. Fallentin N, Jensen BR, Byström S, SjØgaard G. Role of potassium in the reflex regulation of blood pressure during static exercise in man. J Physiol (Lond) 1992;451:643–651.

    Google Scholar 

  71. MacLean DA, Imadojemu VA, Sinoway LI. Interstitial pH, K., lactate and phosphate determined with MSNA during exercise in humans. Am J Physiol (Regulatory, Integrative and Comparative Physiology) 2000;278(3):Rxxx–Rxxx

    Google Scholar 

  72. McClain J, Hardy JC, Sinoway LI. Forearm compression during exercise increases sympathetic nerve traffic. J Appl Physiol 1994;77(6):2612–2617.

    Google Scholar 

  73. Batman BA, Hardy JC, Leuenberger UA, Smith MB, Yang QX, Sinoway LI. Sympathetic nerve activity during prolonged rhythmic forearm exercise. J Appl Physiol 1994;76(3):1077–1081.

    Google Scholar 

  74. Herr MD, Imadojemu V, Kunselman AR, Sinoway LI. Characteristics of the muscle mechanoreflex during quadriceps contractions in humans. J Appl Physiol 1999;86(2):767–772.

    Google Scholar 

  75. McClain J, Hardy C, Enders B, Smith M, Sinoway L. Limb congestion and sympathoexcitation during exercise: Implications for congestive heart failure. J Clin Invest 1993;92(5):2353–2359.

    Google Scholar 

  76. Zelis R, Flaim SF. Alteration in vasomotor tone in congestive heart failure. Prog Cardiovasc Dis 1982; 24:437–459.

    Google Scholar 

  77. Arnold JMO, Ribeiro JP, Colucci WS. Muscle blood flow during forearm exercise in patients with severe heart failure. Circulation 1990;82:465–472.

    Google Scholar 

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

    Google Scholar 

  79. Massie B, Conway M, Yonge R, Frostick S, Ledingham J, Sleight P, Radda G, Rajagopalan B. Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow. Circulation 1987;76(5):1009–1019.

    Google Scholar 

  80. Wilson JR, Fink L, Maris J, Ferraro N, Power-Vanwart J, Eleff S, Chance B. Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance. Circulation 1985;71(1):57–62.

    Google Scholar 

  81. Wilson JR, Wiener DH, Fink LI, Ferraro N. Vasodilatory behavior of skeletal muscle arterioles in patients with nonedematous chronic heart failure. Circulation 1986;74(4):775–779.

    Google Scholar 

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

    Google Scholar 

  83. Zelis R, Mason DT, Braunwald E. 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 1968;47(4): 960–970.

    Google Scholar 

  84. Longhurst J, Gifford W, Zelis R. Impaired forearm oxygen consumption during static exercise in patients with congestive heart failure. Circulation 1976;54(3):477–480.

    Google Scholar 

  85. Sullivan MJ, Knight JD, Higginbotham MB, Cobb FR. 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 1989;80:769–781.

    Google Scholar 

  86. LeJemtel TH, Maskin CS, Lucido D, Chadwick BJ. Failure to augment maximal limb blood flow in response to one-leg versus two-leg exercise in patients with severe heart failure. Circulation 1986;74(2):245–251.

    Google Scholar 

  87. Magnusson G, Kaijser L, Sylvèn C, Karlberg K-E, Isberg B, Saltin B. Peak skeletal muscle perfusion is maintained in patients with chronic heart failure when only a small muscle mass is exercised. Cardiovasc Res 1997;33(2):297–306.

    Google Scholar 

  88. Musch TI, Terrell JA. Skeletal muscle blood flow abnormalities in rats with a chronic myocardial infarction: rest and exercise. Am J Physiol 1992;262 (Heart Circ. Physiol. 31):H411–H419.

    Google Scholar 

  89. Drexler H, Faude F, Honig S, Just H. Blood flow distribution within skeletal muscle during exercise in the presence of chronic heart failure: effect of milrinone. Circulation 1987;76:1344–1352.

    Google Scholar 

  90. Rengo F, Trimarco B, Chiariello M, Sacca L, Violini R, Rasetti G, Ferro G. Relation between cholinergic and histaminergic components in reflex vasodilatation in the dog. Am J Physiol 1978;234 (Heart Circ. Physiol. 3):H305–H311.

    Google Scholar 

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

    Google Scholar 

  92. Kaiser L, Spickard RC, Olivier NB. Heart failure depresses endothelium-dependent responses in canine femoral artery. Am J Physiol 1989;256: H962–H967.

    Google Scholar 

  93. Shoemaker JK, Naylor HL, Hogeman CS, Sinoway LI. Blood flow dynamics in heart failure. Circulation 1999;99(23):3002–3008.

    Google Scholar 

  94. Sterns DA, Ettinger SM, Gray KS, Whisler SK, Mosher TJ, Smith MB, Sinoway LI. Skeletal muscle metaboreceptor exercise responses are attenuated in heart failure. Circulation 1991;84(5):2034–2039.

    Google Scholar 

  95. Piepoli M, Clark AL, Volterrani M, Adamopoulos S, Sleight P, Coats AJS. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure. Effects of physical training. Circulation 1996;93(5):940–952.

    Google Scholar 

  96. Silber DH, Sutliff G, Yang QX, Smith MB, Sinoway LI, Leuenberger UA. Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure. J Appl Physiol 1998;84(5):1551–1559.

    Google Scholar 

  97. Delp MD, Duan C, Mattson JP, Musch TI. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure. J Appl Physiol 1997;83(4):1291–1299.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  101. Sullivan MJ, Green HJ, Cobb FR. Skeletal muscle biochemistry and histology in ambulatory patients with chronic heart failure. Circulation 1990;81:518–527.

    Google Scholar 

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

    Google Scholar 

  103. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation 1986;73(4):615–621.

    Google Scholar 

  104. Hambrecht R, Fiehn E, Yu J, Niebauer J, Weigl C, Hilbrich L, Adams V, Riede V, Schuler G. 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 1997;29(5):1067–1073.

    Google Scholar 

  105. Demopoulos L, Yeh M, Gentilucci M, Testa M, Bijou R, Katz SD, Mancini D, Jones M, LeJemtel TH. Nonselective beta-adrenergic blockade with carvedilol does not hinder the benefits of exercise training in patients with congestive heart failure. Circulation 1997;95(7):1764–1767.

    Google Scholar 

  106. Minotti JR, Johnson EC, Hudson TL, Zuroske G, Murata G, Fukushima E, Cagle TG, Chick TW, Massie BM, Icenogle MV. Skeletal muscle response to exercise training in congestive heart failure. J Clin Invest 1990;86(3):751–758.

    Google Scholar 

  107. Sullivan MJ, Higginbotham MB, Cobb FR. Exercise training in patients with severe left ventricular dysfunction. Hemodynamic and metabolic effects. Circulation 1988;78:506–515.

    Google Scholar 

  108. Sundberg CJ. Exercise and training during graded leg ischaemia in healthy man with special reference to effects on skeletal muscle. Acta Physiol Scand 1994;150(Suppl. 615):1–50.

    Google Scholar 

  109. Yang HT, Ogilvie RW, Terjung RL. Peripheral adaptations in trained aged rats with femoral artery stenosis. Circ Res 1994;74:235–243.

    Google Scholar 

  110. Clausen JP. Circulatory adjustments to dynamic exercise and effect of physical training in normal subjects and in patients with coronary artery disease. Prog Cardiovasc Dis 1976;18(6):459–495.

    Google Scholar 

  111. Gollnick PD, King DW. Effect of exercise and training on mitochondria of rat skeletal muscle. Am J Physiol 1969;216(6):1502–1509.

    Google Scholar 

  112. Saltin B, Rowell LB. Functional adaptations to physical activity and inactivity. Federation Proc 1980;39(5):1506–1513.

    Google Scholar 

  113. Saltin B, Gollnick PD. Skeletal muscle adaptability: significance for metabolisms and performance. In Handbook of Physiology?Skeletal Muscle, ed. J.T. Shepherd and F.M. Abboud. Chapter, pp. 555–631. Baltimore: Waverly Press, Inc., 1983.

    Google Scholar 

  114. Sinoway LI, Rea RF, Mosher TJ, Smith MB, Mark AL. Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans. J Clin Invest 1992;89(6):1875–1884.

    Google Scholar 

  115. Mostoufi-Moab S, Widmaier EJ, Cornett JA, Gray K, Sinoway LI. Forearm training reduces the exercise pressor reflex during ischemic rhythmic handgrip. J Appl Physiol 1998;84(1):277–283.

    Google Scholar 

  116. Minotti JR, Pillay P, Oka R, Wells L, Christoph I, Massie BM. Skeletal muscle size: relationship to muscle function in heart failure. J Appl Physiol 1993;75(1):373–381.

    Google Scholar 

  117. Minotti JR, Pillay P, Chang L, Wells L, Massie BM. Neurophysiological assessment of skeletal muscle fatigue in patients with congestive heart failure. Circulation 1992;86:903–908.

    Google Scholar 

  118. Ohtsubo M, Yonezawa K, Nishijima H, Okita K, Hanada A, Kohya T, Murakami T, Kitabatake A. Metabolic abnormality of calf skeletal muscle is improved by localised muscle training without changes in blood flow in chronic heart failure. Heart 1997;78(5):437–443.

    Google Scholar 

  119. Adamopoulos S, Coats AJ, Brunotte F, Arnolda L, Meyer T, Thompson CH, Dunn JF, Stratton J, Kemp GJ, Radda GK, et al. Physical training improves skeletal muscle metabolism in patients with chronic heart failure.J Am Coll Cardiol 1993;21(5):1101–1106.

    Google Scholar 

  120. Kiilavuori K, Toivonen L, Naveri H, Leinonen H. Reversal of autonomic derangements by physical training in chronic heart failure assessed by heart rate variability. Eur Heart J 1995;16(4):490–495.

    Google Scholar 

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  1. Department of Medicine, Section of Cardiology, Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania, 17033

    Mazhar H. Khan &  Lawrence I. Sinoway

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Khan, M.H., Sinoway, L.I. Muscle Reflex Control of Sympathetic Nerve Activity in Heart Failure: The Role of Exercise Conditioning. Heart Fail Rev 5, 87–100 (2000). https://doi.org/10.1023/A:1009802308872

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