Exercise hyperventilation in patients with McArdle's disease

1982 ◽  
Vol 52 (4) ◽  
pp. 991-994 ◽  
Author(s):  
J. M. Hagberg ◽  
E. F. Coyle ◽  
J. E. Carroll ◽  
J. M. Miller ◽  
W. H. Martin ◽  
...  
Keyword(s):  
Blood Lactate ◽  
Normal Subjects ◽  
O2 Consumption ◽  
Intense Exercise ◽  
Mcardle's Disease ◽  
Normal Individuals ◽  
Mcardle’S Disease ◽  
Muscle Phosphorylase ◽  
Lactate Levels ◽  
End Tidal

This study was undertaken to determine if patients who lack muscle phosphorylase (i.e., McArdle's disease), and therefore the ability to produce lactic acid during exercise, demonstrate a normal hyperventilatory response during progressive incremental exercise. As expected these patients did not increase their blood lactate above resting levels, whereas the blood lactate levels of normal subjects increased 8- to 10-fold during maximal exercise. The venous pH of the normal subjects decreased markedly during exercise that resulted in hyperventilation. The patients demonstrated a distinct increase in ventilation with respect to O2 consumption similar to that seen in normal individuals during submaximal exercise. However their hyperventilation resulted in an increase in pH because there was no underlying metabolic acidosis. End-tidal partial pressures of O2 and CO2 also reflected a distinct hyperventilation in both groups at approximately 70–85% maximal O2 consumption. These data show that hyperventilation occurs during intense exercise, even when there is no increase in plasma [H+]. Since arterial CO2 levels were decreasing and O2 levels were increasing during the hyperventilation, it is possible that nonhumoral stimuli originating in the active muscles or in the brain elicit the hyperventilation observed during intense exercise.

Exercise and recovery ventilatory and VO2 responses of patients with McArdle's disease

1990 ◽  
Vol 68 (4) ◽  
pp. 1393-1398 ◽  
Author(s):  
J. M. Hagberg ◽  
D. S. King ◽  
M. A. Rogers ◽  
S. J. Montain ◽  
S. M. Jilka ◽  
...  
Keyword(s):  
Blood Lactate ◽  
High Intensity ◽  
Maximal Exercise ◽  
Matched Control ◽  
Slow Component ◽  
High Intensity Exercise ◽  
O2 Consumption ◽  
Control Subjects ◽  
Mcardle's Disease ◽  
Mcardle’S Disease

This study was designed to determine whether patients with McArdle's disease, who do not increase their blood lactate levels during and after maximal exercise, have a slow “lactacid” component to their recovery O2 consumption (VO2) response after high-intensity exercise. VO2 was measured breath by breath during 6 min of rest before exercise, a progressive maximal cycle ergometer test, and 15 min of recovery in five McArdle's patients, six age-matched control subjects, and six maximal O2 consumption- (VO2 max) matched control subjects. The McArdle's patients' ventilatory threshold occurred at the same relative exercise intensity [71 +/- 7% (SD) VO2max] as in the control groups (60 +/- 13 and 70 +/- 10% VO2max) despite no increase and a 20% decrease in the McArdle's patients' arterialized blood lactate and H+ levels, respectively. The recovery VO2 responses of all three groups were better fit by a two-, than a one-, component exponential model, and the parameters of the slow component of the recovery VO2 response were the same in the three groups. The presence of the same slow component of the recovery VO2 response in the McArdle's patients and the control subjects, despite the lack of an increase in blood lactate or H+ levels during maximal exercise and recovery in the patients, provides evidence that this portion of the recovery VO2 response is not the result of a lactacid mechanism. In addition, it appears that the hyperventilation that accompanies high-intensity exercise may be the result of some mechanism other than acidosis or lung CO2 flux.

Disposal of blood [1-13C]lactate in humans during rest and exercise

1986 ◽  
Vol 60 (1) ◽  
pp. 232-241 ◽  
Author(s):  
R. S. Mazzeo ◽  
G. A. Brooks ◽  
D. A. Schoeller ◽  
T. F. Budinger
Keyword(s):  
Blood Lactate ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Curvilinear Relationship ◽  
O2 Consumption ◽  
Lactate Oxidation ◽  
Respiratory Parameters ◽  
Steady Rate ◽  
Lactate Levels

Lactate irreversible disposal (RiLa) and oxidation (RoxLa) rates were studied in six male subjects during rest (Re), easy exercise [EE, 140 min of cycling at 50% of maximum O2 consumption (VO2max)] and hard exercise (HE, 65 min at 75% VO2max). Twenty minutes into each condition, subjects received a Na+-L(+)-[1–13C]lactate intravenous bolus injection. Blood was sampled intermittently from the contralateral arm for metabolite levels, acid-base status, and enrichment of 13C in lactate. Expired air was monitored continuously for determination of respiratory parameters, and aliquots were collected for determination of 13C enrichment in CO2. Steady-rate values for O2 consumption (VO2) were 0.33 +/- 0.01, 2.11 +/- 0.03, and 3.10 +/- 0.03 l/min for Re, EE, and HE, respectively. Corresponding values of blood lactate levels were 0.84 +/- 0.01, 1.33 +/- 0.05, and 4.75 +/- 0.28 mM in the three conditions. Blood lactate disposal rates were significantly correlated to VO2 (r = 0.78), averaging 123.4 +/- 20.7, 245.5 +/- 40.3, and 316.2 +/- 53.7 mg X kg-1 X h-1 during Re, EE, and HE, respectively. Lactate oxidation rate was also linearly related to VO2 (r = 0.81), and the percentage of RiLa oxidized increased from 49.3% at rest to 87.0% during exercise. A curvilinear relationship was found between RiLa and blood lactate concentration. It was concluded that, in humans, 1) lactate disposal (turnover) rate is directly related to the metabolic rate, 2) oxidation is the major fate of lactate removal during exercise, and 3) blood lactate concentration is not an accurate indicator of lactate disposal and oxidation.

The clinical diagnosis of McArdle's disease: Identification of another family with deficiency of muscle phosphorylase

Neurology ◽  
1966 ◽  
Vol 16 (1) ◽  
pp. 93-93 ◽  
Author(s):  
L. P. Rowland ◽  
R. E. Lovelace ◽  
D. L. Schotland ◽  
S. Araki ◽  
P. Carmel
Keyword(s):  
Clinical Diagnosis ◽  
Disease Identification ◽  
Mcardle's Disease ◽  
Mcardle’S Disease ◽  
Muscle Phosphorylase

Assessment of rebreathing O2 consumption in humans with normal and diseased lungs

1990 ◽  
Vol 68 (4) ◽  
pp. 1443-1452 ◽  
Author(s):  
M. C. Kallay ◽  
R. W. Hyde ◽  
R. J. Smith
Keyword(s):  
Steady State ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Pulse Rate ◽  
Obstructive Lung Disease ◽  
Pulmonary Function Tests ◽  
Normal Subjects ◽  
O2 Consumption ◽  
O2 Uptake ◽  
End Tidal

We investigated sources of error in estimating steady-state O2 consumption (VO2ss) by calculating O2 uptake from an anesthesia bag containing O2, He, and N2 during 10-20 s of rebreathing (VO2rb). In 11 normal resting subjects, VO2rb calculated with end-tidal sampling overestimated VO2ss by 16 +/- 15% (SD) (P less than 0.003). This error was proportional to the increase in pulse rate during rebreathing, so that pulse-corrected VO2rb slightly underestimated VO2ss by 2.1 +/- 12.2% (P = 0.66) in the six subjects who rebreathed 28% O2 in the rebreathing bag but significantly underestimated VO2ss by 7.5 +/- 6.7% (P less than 0.04) in the six subjects who rebreathed 21% O2 in the rebreathing bag. During exercise, VO2rb underestimated VO2ss by 4 +/- 12% (P less than 0.001) and by 7 +/- 6% at O2 consumptions greater than 2,000 ml/min if O2 in the rebreathing bag was kept above 20% throughout rebreathing. We found that VO2rb calculated with end-tidal gas concentrations underestimated VO2ss by 1-43% in patients with moderate-to-severe obstructive lung disease, with even greater errors when mixed expired samples were used. The magnitude of the discrepancy correlated poorly with abnormalities in standard pulmonary function tests. Based on these data, VO2rb closely approximates VO2ss in normal subjects, provided hypoxia during rebreathing is avoided and cardiac acceleration from rebreathing is taken into account during resting measurement.

The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue

1986 ◽  
Vol 61 (2) ◽  
pp. 391-401 ◽  
Author(s):  
S. F. Lewis ◽  
R. G. Haller
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fatigue ◽  
Muscle Afferents ◽  
Common Denominator ◽  
Circulatory Response ◽  
Mcardle's Disease ◽  
O2 Transport ◽  
Mcardle’S Disease ◽  
Muscle Phosphorylase ◽  
Response To Exercise

Muscle phosphorylase deficiency (McArdle's disease) has conventionally been considered a disorder of glycogenolysis, and the associated impairment in oxidative metabolism has been largely overlooked. Muscle glycogen normally is the primary oxidative fuel at exercise work loads requiring more than 75–80% of maximal O2 uptake (VO2max). Evidence is presented to support the hypothesis that a limited flux through the Embden-Myerhof pathway in McArdle's disease reduces the capacity to generate NADH required to support a normal VO2max. The extent of the oxidative defect is substrate dependent; i.e., it can be partially corrected by increasing the availability of alternative oxidative substrates (e.g., glucose, free fatty acids) to working muscle. Experiments employing modification of substrate availability closely link the hyperkinetic circulatory response to exercise (i.e., an abnormally large increase in O2 transport to skeletal muscle) and the premature muscle fatigue and cramping of McArdle patients with their oxidative impairment and suggest that a metabolic common denominator in these abnormal responses may be a pronounced decline in the muscle phosphorylation potential ([ATP]/[ADP][Pi]). The hyperkinetic circulation likely is mediated by the local effects on metabolically sensitive skeletal muscle afferents and vascular smooth muscle of K+, Pi, or adenosine or a combination of these substances released excessively from working skeletal muscle. The premature muscle fatigue and cramping of McArdle patients does not appear to be due to depletion of ATP but is associated with an increased accumulation of Pi and probably ADP in skeletal muscle. Accumulations of Pi and ADP are known to inhibit the myofibrillar, Ca2+, and Na+-K+-ATPase reactions.

scholarly journals Myophosphorylase Deficiency (McArdle's Disease): Report of a Family

1976 ◽  
Vol 3 (3) ◽  
pp. 175-179 ◽  
Author(s):  
M. Zafar Mahmud ◽  
R. Rodney Howell ◽  
Roger E. Stevenson ◽  
John Gilroy
Keyword(s):  
Clinical Features ◽  
Quantitative Estimation ◽  
Enzyme Systems ◽  
Mcardle's Disease ◽  
The Family ◽  
Mcardle’S Disease ◽  
Lactate Levels ◽  
Biochemical Abnormalities

SUMMARY:The clinical and biochemical findings are presented of two brothers suffering from McArdle's Disease (Myophosphorylase Deficiency). Tissue enzyme estimations and lactate levels were done in affected and non-affected members of the family. Affected members showed absence of phosphorylase enzyme by histochemical and quantitative estimation. No quantitative abnormalities were found in other enzyme systems of glycolytic pathways in the family investigated. Various other aspects of clinical features, biochemical abnormalities and inheritance are discussed.

Muscle fatigue in McArdle's disease studied by 31P-NMR: effect of glucose infusion

1985 ◽  
Vol 59 (6) ◽  
pp. 1991-1994 ◽  
Author(s):  
S. F. Lewis ◽  
R. G. Haller ◽  
J. D. Cook ◽  
R. L. Nunnally
Keyword(s):  
Muscle Fatigue ◽  
31P Nmr ◽  
Glucose Infusion ◽  
Strenuous Exercise ◽  
Intravenous Glucose ◽  
Mcardle's Disease ◽  
Mcardle’S Disease ◽  
Muscle Phosphorylase ◽  
Muscle Energy Metabolism ◽  
Forearm Muscle

In muscle phosphorylase deficiency (McArdle's disease) there is an abnormally rapid fatigue during strenuous exercise. Increasing substrate availability to working muscle can improve exercise tolerance but the effect on muscle energy metabolism has not been studied. Using phosphorus-31 nuclear magnetic resonance (31P-NMR) we examined forearm muscle ATP, phosphocreatine (PCr), inorganic phosphate (Pi) and pH in a McArdle patient (MP) and two healthy subjects (HS) at rest and during intermittent maximal effort handgrip contractions under control conditions (CC) and during intravenous glucose infusion (GI). Under CC, MP gripped to impending forearm muscle contracture in 130 s with a marked decline in muscle PCr and a dramatic elevation in Pi. During GI, MP exercised easily for greater than 420 s at higher tensions and with attenuated PCr depletion and Pi accumulation. In HS, muscle PCr and Pi changed more modestly and were not affected by GI. In MP and HS, ATP changed little or not at all with exercise. The results suggest that alterations in the levels of muscle PCr and Pi but not ATP are involved in the muscle fatigue in McArdle's disease and the improved exercise performance during glucose infusion.

Induced lactacidemia does not affect postexercise O2 consumption

1988 ◽  
Vol 65 (3) ◽  
pp. 1045-1049 ◽  
Author(s):  
D. A. Roth ◽  
W. C. Stanley ◽  
G. A. Brooks
Keyword(s):  
Blood Flow ◽  
Blood Lactate ◽  
Time Course ◽  
Cycle Ergometer ◽  
Base Line ◽  
O2 Consumption ◽  
Total Recovery ◽  
Lactate Levels ◽  
Male Subjects ◽  
Blood Lactate Levels

To study the effects of circulatory occlusion on the time course and magnitude of postexercise O2 consumption (VO2) and blood lactate responses, nine male subjects were studied twice for 50 min on a cycle ergometer. On one occasion, leg blood flow was occluded with surgical thigh cuffs placed below the buttocks and inflated to 200 mmHg. The protocol consisted of a 10-min rest, 12 min of exercise at 40% peak O2 consumption (VO2 peak), and a 28-min resting recovery while respiratory gas exchange was determined breath by breath. Occlusion (OCC) spanned min 6-8 during the 12-min work bout and elicited mean blood lactate of 5.2 +/- 0.8 mM, which was 380% greater than control (CON). During 18 min of recovery, blood lactate after OCC remained significantly above CON values. VO2 was significantly lower during exercise with OCC compared with CON but was significantly higher during the 4 min of exercise after cuff release. VO2 was higher after OCC during the first 4 min of recovery but was not significantly different thereafter. Neither total recovery VO2 (gross recovery VO2 with no base-line subtraction) nor excess postexercise VO2 (net recovery VO2 above an asymptotic base line) was significantly different for OCC and CON conditions (13.71 +/- 0.45 vs. 13.44 +/- 0.61 liters and 4.93 +/- 0.26 vs. 4.17 +/- 0.35 liters, respectively). Manipulation of exercise blood lactate levels had no significant effect on the slow ("lactacid") component of the recovery VO2.

Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease

1990 ◽  
Vol 69 (4) ◽  
pp. 1231-1235 ◽  
Author(s):  
K. Sahlin ◽  
N. H. Areskog ◽  
R. G. Haller ◽  
K. G. Henriksson ◽  
L. Jorfeldt ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Subjects ◽  
Adenine Nucleotide ◽  
Tricarboxylic Acid Cycle ◽  
Work Load ◽  
Maximal Heart Rate ◽  
Mcardle's Disease ◽  
Mcardle’S Disease ◽  
Arterial Plasma ◽  
Lactate Levels

Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.

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