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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients

¹Department of Medicine, Nephrology Section, San Francisco Veterans Affairs Medical Center, San Francisco; ²Department of Medicine, University of California, San Francisco; ³Northern California Institute for Research and Education, San Francisco, California; and ⁴Exercise Science Department, University of Massachusetts, Amherst, Massachusetts

Submitted 15 March 2005 ; accepted in final form 11 May 2005

Dialysis patients have severe exercise limitations related to metabolic disturbances, but muscle fatigue has not been well studied in this population. We investigated the magnitude and mechanisms of fatigue of the ankle dorsiflexor muscles in patients on maintenance hemodialysis. Thirty-three dialysis patients and twelve healthy control subjects performed incremental isometric dorsiflexion exercise, beginning at 10% of their maximal voluntary contraction (MVC) and increasing by 10% every 2 min. Muscle fatigue (fall of MVC), completeness of voluntary activation, and metabolic responses to exercise were measured. Before exercise, dialysis subjects exhibited reduced strength and impaired peripheral activation (lower compound muscle activation potential amplitude) but no metabolic perturbation. During exercise, dialysis subjects demonstrated threefold greater fatigue than controls with evidence of central activation failure but no change in peripheral activation. All metabolic parameters were significantly more perturbed at end exercise in dialysis subjects than in controls, including lower phosphocreatine (PCr) and pH, and higher P_i, P_i/PCr, and H₂PO₄^–. Oxidative potential was markedly lower in patients than in controls [62.5 (SD 27.2) vs. 134.6 (SD 31.7), P < 0.0001]. Muscle fatigue was negatively correlated with oxidative potential among dialysis subjects (r = –0.52, P = 0.04) but not controls. Changes in central activation ratio were also correlated with muscle fatigue in the dialysis subjects (r = 0.59, P = 0.001) but not the controls. This study provides new information regarding the excessive muscular fatigue of dialysis patients and demonstrates that the mechanisms of this fatigue include both intramuscular energy metabolism and central activation failure.

oxidative phosphorylation; central fatigue; electromyography; muscle activation; ³¹P magnetic resonance spectroscopy

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