The exercise metaboreflex is maintained in the absence of muscle acidosis: insights from muscle microdialysis in humans with McArdle's disease

Abstract

1. In McArdle's disease, muscle glycogenolysis is blocked, which results in absent lactate and enhanced ammonia production in working muscle. Using McArdle patients as an experimental model, we studied whether lactate and ammonia could be mediators of the exercise pressor reflex. 2. Changes in muscle interstitial ammonia and lactate were compared with changes in blood pressure and muscle sympathetic nerve activity (MSNA) during static arm flexor exercise at 30% of maximal contraction force. Muscle interstitial changes in lactate and ammonia were assessed by microdialysis of the biceps muscle, and MSNA by peroneal nerve microneurography, in six McArdle patients and 11 healthy, matched controls. One McArdle patient also had myoadenylate deaminase deficiency, a condition associated with abolished ammonia production in exercise. 3. Exercise-induced increases were higher in McArdle patients vs. controls for MSNA (change of 164 +/- 71 vs. 59 +/- 19%) and blood pressure (change of 47 +/- 7 vs. 38 +/- 4 mmHg). Interstitial lactate increased in controls (peak change 1.3 +/- 0.2 mmol x l(-1)) and decreased in McArdle patients (peak change -0.5 +/- 0.1 mmol x l(-1)) during and after exercise. Interstitial ammonia did not change during exercise in either group, but was higher post-exercise in McArdle patients, except in the patient with myoadenylate deaminase deficiency who had a flat ammonia response. This patient had an increase in MSNA and blood pressure comparable to other patients. MSNA and blood pressure responses were maintained during post-exercise ischaemia in both groups, indicating that sympathetic activation was caused, at least partly, by a metaboreflex. 4. In conclusion, changes in muscle interstitial lactate and ammonia concentrations during and after exercise are temporally dissociated from changes in MSNA and blood pressure in both patients with McArdle's disease and healthy control subjects. This suggests that muscle acidification and changes in interstitial ammonia concentration are not mediators of sympathetic activation during exercise.

Figure 1

Changes during and after exercise in interstitial lactate and dialysate ammonia concentrations in biceps muscle of six patients with McArdle's disease and six healthy matched controls. Changes are from pre-exercise resting levels to: (1) exercise, (2) the first 4 min of recovery from exercise and (3) at rest 1 h following static arm flexor exercise, in probes from which data could be obtained at all time points. The number of probes evaluated at all time points was (McArdle/control) 6/7 for ammonia and 4/3 for lactate. Ammonia results do not include data from the patient with combined myophosphorylase and myoadenylate deaminase deficiency. Ammonia data from this patient are shown separately in Table 2. Values are means ±s.e.m.† Significantly different change from pre-exercise rest in all patients vs. controls. * Significantly different change from pre-exercise rest in all subjects.

Figure 4

Plasma concentrations of lactate and ammonia in cubital venous blood at rest and after exhaustive static handgrip exercise at 30 % of MVC in six patients with McArdle's disease (□) and six matched healthy controls (○). Values are means ±s.e.m. Ammonia data from the patient with combined myophosphorylase and myoadenylate deaminase deficiency (▵) are shown separately from those of the other five McArdle patients in the top panel. All other data points are based on findings in six subjects in each group.

Figure 2

Integrated neurograms of muscle sympathetic nerve activity and force development during static arm flexor exercise at 30 % of MVC in a patient with McArdle's disease and a corresponding, healthy, control subject.

Figure 3

MSNA expressed as bursts min⁻¹ (BPM) and mean arterial blood pressure in three patients with McArdle's disease and five healthy matched subjects at rest, at the end of 2-3 min of static elbow flexing exercise at 30 % of MVC (Exercise), during post-exercise ischaemia (PEI) and during recovery. Values are means ±s.e.m.* Significantly different from Rest values in all subjects. All data points are based on observation in three McArdle patients and five healthy subjects, except blood pressure data, which are missing for one healthy subject, and recovery data, which are missing for one of the McArdle patients.