AND SCOTT L. HELLER. Section of Applied Physiology, Department of Medicine, Jerry Lewis Neuromuscular Research Center,. Department of Neurology, and ...
Exercise and recovery ventilatory and of patients with McArdle’s disease
VO,
responses
JAMES M. HAGBERG, DOUGLAS S. KING, MARC A. ROGERS, SCOTT J. MONTAIN, SARAH M. JILKA, WENDY M. KOHRT, AND SCOTT L. HELLER Section of Applied Physiology, Department of Medicine, Jerry Lewis Neuromuscular Research Center, Department of Neurology, and Irene Walter Johnson Institute of Rehabilitation, Washington University School of Medicine, St. Louis, Missouri 63110
MARC A. ROGERS, M. KOHRT, AND Exercise and recovery ventilatory and vo2 responses of patients with McArdle’s disease. J. Appl. Physiol. 68(4): 1393~1398,1990.-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 (VO?) response after high-intensity exercise. iTo 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 Oz consumption(VO, mBX) matched control subjects. The McArdle’s patients’ ventilatory threshold occurred at the same relative exercise intensity [71 t 7% (SD) VO ‘Lmax] as in the control groups (60 ? 13 and 70 t 10% VO;! mAX) 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 VO, response were the same in the three groups. The presence of the same slow component of the recovery Voz 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 VO, 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 CO, flux. HAGBERG, JAMES SCOTT J. MONTAIN, SCOTT L. HELLER.
M., DOUGLAS S. KING, SARAH M. JILKA, WENDY
lactate; pH; control of ventilation; ery oxygen consumption
oxygen debt; lactacid recov-
OF O2 CONSUMPTION (vO2) to resting levels after high-intensity exercise has been known for 75 years to be best described by a two-component exponential model (15). Approximately 15 years after the initial description by Krogh and Lindhard (15), Meakins and Long (20) reported that a patient with circulatory failure had higher blood lactate levels during and after exercise and had a longer recovery time for Vo2 after exercise than healthy individuals. In 1933 Margaria and co-workers (18) proposed that the second, slower component of the recovery VO, response after high-intensity exercise be termed the “lactacid” component because of the similarity between its time course and that of the decline in blood lactate levels. Thus for almost 40 years THE RECOVERY
0161-7567/90
$1.50 Copyright
it was generally accepted that this component of the recovery VOW response was a result of the excessenergetic costs associated with the metabolism of lactate. However, a number of investigators have provided evidence that factors other than the metabolism of lactate may underlie this component of the recovery Tjop response (1, 4, 7, 12, 22, 24). These studies have used physiological manipulations to alter blood lactate levels and have reported a relative dissociation between blood lactate levels and the second component of the recovery vo2 response (12, 22, 24). In the present study patients with McArdle’s disease were studied because they lack muscle phosphorylase and therefore do not increase their blood lactate levels during ischemic forearm (19) or maximal dynamic exercise (10, 17, 19). If these patients have a second component to their recovery Vo2 response that is the same as that of control subjects, it would indicate a complete dissociation of blood lactate levels and the second component of the recovery vo2 response, which would provide definitive evidence that the second component of the recovery \jo2 response after high-intensity exercise is not the result of excess VOWassociated with the metabolism of lactate. Because a progressive exercise test was part of this study, we also sought to study the hyperventilation that accompanies high-intensity exercise in McArdle’s diseasepatients (10). To extend our previous study (10) we sought to determine if arterial pH, Pco~, and lactate levels, and the patients’ apprehension and/or perception of muscle pain might underlie their hyperventilation during high-intensity exercise. METHODS
Subjects (Table 1). Five patients with McArdle’s disease, documented by a lack of histochemical and/or biochemical phosphorylase activity in muscle biopsy samples and a lack of increase in blood lactate during an incremental forearm exercise test (14, 19), were studied. One female underwent two exercise tests, and both were included in the analyses of recovery VOWresponses. One male was also a subject in our previous report on exercise hyperventilation in McArdle’s disease patients (10). Six age-matched control subjects were also studied. They were healthy normally active individuals who were not undergoing a regular training program. Because
63 1990 the American
Physiological
Society
1393
1394
EXERCISE
AND
RECOVERY
RESPONSES
1. Characteristics of the three subject groups
TABLE
McArdle’s Patients
Sex Age, yr Weight, Values
kg
are means
3M/2F 28t11 71.6+11.4
Controls Young
4M/2F 28*4 72.2t16.6
Old
3M/3F 66t2 71.8k19.5
k SD.
McArdle’s diseasepatients have low \jo2 maxvalues relative to their untrained yet healthy peers (10, 17) and because fitness can affect exercise and recovery Vo2, ventilatory, and heart rate responses (5, ll), a second control group of older untrained individuals whose ~~~~~~~ more closely matched those of the patients was also studied. The older healthy subjects had previously undergone maximal treadmill testing as part of another project and displayed no evidence of overt coronary artery disease. The protocol was approved by the Washington University School of Medicine Institutional Review Board, and all subjects provided their written informed consent to participate after the study and its hazards had been described to them. Exercise testing. All subjects completed a progressive exercise test on a cycle ergometer; exercise was terminated when the subject was unable to continue, which in nearly all caseswas the result of generalized fatigue. The test began with 6 min of quiet rest while the subject sat on the ergometer. After this, the subjects exercised for 4 min at a work rate selected to elicit -3O-40% of their estimated VOW max.Work rates were then increased every minute by 5-10 W in the patients and by 10-25 W in the control subjects to bring about exhaustion within 9-12 min of exercise. During exercise the subjects pedaled at 60-70 rpm. After the cessation of exercise the subjects remained seated on the cycle ergometer for a 15min recovery period. \jo2, CO, production (ho,), ventilation (VE), and endtidal 0, (PET~J and CO2 (PETE?,) tensions were measured on a breath-by-breath basis with the use of the algorithms of Beaver et al. (2) throughout the preexercise rest, exercise, and recovery periods by the use of a digital computer, a Perkin-Elmer respiratory mass spectrometer, and a Fleisch heated pneumotachometer connected to a Validyne pressure transducer. The ventilatory threshold was determined as the point where PETIT and the ventilatory equivalent for 0, (VE/~O~) increased out of proportion to the changes at lower work rates and where they continued to increase disproportionately with further work rate increases (25). An electrocardiogram (ECG) tracing was recorded to determine heart rate in the last 10 s of each minute throughout the protocol. The McArdle’s patients and young control subjects had a catheter placed retrograde in a dorsal vein in the hand. This hand was kept in a heated chamber so that arterialized blood samples could be drawn each minute of the protocol (6). The pH and PCO~ of these samples were measured on an Instrumentation Laboratory model 813 pH/blood gas analyzer, and lactate was measured with the use of an enzymatic technique (8). Subjects in the older control group had a catheter placed in an antecubital vein to draw samples for blood lactate measure-
OF
McARDLE’S
PATIENTS
ments. The McArdle’s disease patients were repeatedly asked during exercise if they were experiencing any perceptible muscle pain and they were questioned after completing the protocol concerning any apprehension of impending muscle pain. Curve fitting for the recovery responses. The breathby-breath \joz data for each subject were initially fit to both a one-component exponential model . . vo 2t = vo 2 endex e-kt and a two-component exponential model e-M+ vo$ e-k,t vo zt = v02r where t is the time in minutes after the start of recovery, vozt is the vo2 at time t in excess of the preexercise resting base-line value, Vozendexis the Vo2 at the end of exercise in excess of the preexercise resting base-line value, k is the time constant of the one-component model, Vozr is the magnitude of the rapid component of the recovery Vo2 response of the two-component model, VO; is the magnitude of the slow component of the recovery vo2 response of the two-component model, k, is the time constant of the rapid component of the recovery vo2 response of the two-component model, k is the time constant of the slow component of the recovery Vo2 response of the two-component model, and where, in the two-component model, VO/ plus VO$ must equal VOZendex.The VE, ho2, and heart rate data were also fit to similar models. These models were fit to the breath-by-breath data and the l5-, 30-, and 60-s averages of these breath-bybreath data; the averaged values were analyzed to ensure that the minimal change to be described in the McArdle’s patients and the older control groups (0.9-1.5 l/min for TO,, for example) and the variability that exists between individual breath gas exchange variables (16) did not interact to mathematically obscure actual physiological trends. All values were normalized to the change in the variable for that subject from the preexercise resting base line to the end of exercise. The normalized data from all subjects within a group were fit to the one- and two-component exponential models by the use of the NLIN procedure in the Statistical Analysis System (23). The results of these analyses on the breath-by-breath data and the values derived by averaging for 15, 30, and 60 s were identical in terms of the gas exchange recovery responses. The values presented in Table 3 are those from the 30-s average analyses as they were generally most representative of the different analyses for the various gas exchange variables. The statistical significance of the differences in the curve-fitting variables among the three groups was assessedby the use of the derived 95% confidence intervals for each variable in each group. The statistical significance of the differences among all three groups in the remaining variables was assessedby the use of a priori comparisons within an analysis of variance with the use of the Statistical Analysis System (23).
EXERCISE
AND
RECOVERY
RESPONSES
RESULTS v02 max (Table 2). The McArdle’s patients’ VO, maxwas less than half that of the young control subjects. The . vo 2 rnax of the McArdle’s patients was only one-third lower than that of the older control group. Thus, although this group was not a perfect match for the McArdle’s patients in terms of VOLT,,, it represents a better match than the young control subjects. The maximal heart rates of the McArdle’s patients and young control subjects were not different. Although the respiratory exchange ratio (RER) of the patients during maximal exercise was lower than that of both the young and the older control subjects, it was similar to values reported previously in these patients during maximal exercise (10). These patients have low maximal RER values because they are incapable of oxidizing carbohydrates at high rates, thereby reducing their metabolic respiratory quotient even during maximal exercise. Ventilator-y responses to exercise (Table 2). The McArdle’s patients had qualitatively the same ventilatory responses during submaximal and maximal exercise in terms of PETIT.,, PETE?, Pace,, tidal volume, breathing frequency, ventilation, - and ventilatory equivalents for O2and CO, as both control groups. The end-tidal O2 and CO, values for the McArdle’s patients indicated that they were already hyperventilating somewhat during low levels of exercise (30-60% \j02 max), as has been previ-
2. Maximal and submaximal exercise responsesof the three subject groups
TABLE
McArdle’s Patients __-----___- ____ VE max, l/min Maximal heart rate, beats/ min Rest ~JO?, ml - kg-’ . min-’ VO L' nl:lx~ ml - kg-’ min-’ Vent ilatory equivalent . . during maximal exercise, l/l l
VE/VO,!
VE/ikO~ Ventilator-y % vo,
threshold,
Controls Young
Old
40.9+8.2* 182:s
89.5t27.3 187-+-U
60.6-el4.9 168tl3*
3.3kO.7 14.7k3.8"
3.8rt0.3 33.8t4.0
3.0-eo.5 23.1&4.3*
37.9t12.5 39.7+8.8*
35.1k4.8 27.2k3.0
38.3t2.3 29.9t1.3
71t7
60t13
7OklO
1.28t0.05
1.34t0.13
OF
1.02kO.16"
0.9t0.4
1.3kO.8
7.1t2.0
5.7kO.7
1.4t0.6 1.6*1.6* 1.6t1.6*
1 l.lt1.8
41.7k2.6 33.2_t3.3*
38.6k1.7 46.8t2.8
110*5 120t7
106t4 121t2
10526 123t4
34_+3 26t6*
35,t2 31t2
37*3 3ost3
40t2 33t7*
14 r . . 12 . . 10 . . 8I . 6. . 4. . 2. . 0,
7.4&1.2*
4Ozk2 38t4
Values are means t SD. RER, respiratory exchange ratio. Peak blood lactate level is the highest value for each subject during maximal exercise or the first 10 min of recovery. * Significantly different from both other groups, F < 0.05.
1395
PATIENTS
ously noted by others (13). The McArdle’s patients began to hyperventilate further and the two control groups began to hyperventilate at similar relative work rates. During maximal exercise the McArdle’s patients had the same ventilatory equivalent for OZ and the same PETE, as both control groups. The McArdle’s patients, however, had a larger ventilatory equivalent for CO2 and a lower PETIT, during maximal exercise than both the young and the older control group; they also had lower arterialized PCO~ values than the young control group during maximal exercise. Blood lactate responses(Fig. 1 and Table 2). The blood lactate concentrations of the McArdle’s patients varied from 1.2 to 1.6 mM during the preexercise rest, exercise, and recovery periods, with no values during exercise or recovery being significantly different from the preexercise resting base-line value. The young control group increased their blood lactate levels from rest -‘l-fold by the end of exercise and -II-fold during the first 10 min of recovery. Their blood lactate levels were still >7 mM higher than before exercise after 15 min of recovery following the maximal exercise test. The older control subjects increased their blood lactate levels more than fourfold by the end of exercise and more than fivefold for the first 10 min of recovery after the maximal exercise test. Their blood lactate levels were still 5 mM above resting levels after 15 min of recovery. Blood H+ responses(Fig. 2 and Table 2). The McArdle’s patients decreased their blood H+ levels during maximal exercise by 20% from preexercise rest levels. Their blood H+ levels increased slowly during recovery, but they were still -10% below preexercise rest levels after 15 min of recovery. From rest to maximal exercise the young control subjects increased their blood H+ levels by >20%; their blood H+ levels were highest from 4 to 9 min of recovery when they were -50% above those at rest before exercise. Their blood H+ levels were still 36% above those before exercise after 15 min of recovery. Recovery Vo2 responses(Fig. 3 and Table 3). By 30 s of recovery VO, had decreased in all three groups -40%
,,,;tx
Maximal RER, units Blood lactate, mM Rest Maximal exercise Peak value Arterialized blood H+, lo-” eq/l Rest Maximal exercise PET+ Torr Rest Maximal exercise PET+ Torr Rest Maximal exercise Pa(-o.,, Torr Rest Maximal exercise
McARDLE’S
I
I
I
I
I
1
I
I
I
Rest
o
2
4
6
8
10
12
14
Recovery
I 16
Time (min)
1. Blood lactate levels of the 3 groups at rest before exercise, during maximal exercise (time O), and during 15 min of subsequent recovery. IJ, McArdle’s patients; n , older control subjects; A, young control subjects. Values are means t SD. FIG.
EXERCISE
1396
z
AND RECOVERY
RESPONSES
OF McARDLE’S
PATIENTS
TABLE 3. Characteristics of the two-component exponential model describing the recovery responses
65 r
McArdle’s Patients
Controls Young
Old
vo2
.
+ z
t I 25 I Rest 0
I 2
I 4
I 6
I 8
I
I
I
J
10
12
14
16
Recovery Time (min) 2. H+ levels in arterialized blood of the 2 groups at rest before exercise, during maximal exercise (time 0), and during 15 min of subsequent recovery. See legend of Fig. 1 for explanation of symbols. Values are means k SD. FIG.
(v
00>
120
80 60 40 20 0
0
5
10
15
Recovery Time (min) 3. Relative vo2 responses of the 3 groups during the 15-min recovery period after maximal exercise. Relative change in van is 90~ at that time point normalized for difference between peak-exercise VO, and preexercise rest 60,. See legend of Fig. 1 for explanation of symbols. FIG.
of the way from the peak exercise to the preexercise resting base-line Vop value. From there until 9 min of recovery, on a relative basis, the McArdle’s patients recovered somewhat slayer than the other two groups. By 15 min of recovery Vop had decreased in all three groups to within 3-5% of the preexercise base-line value. In all three groups the two-component model fit the recovery Vo2 responses better than the one-component model as indicated by a 34-85% reduction in the residual sum of squares. The presence of a slow component of the recovery VOWresponse is substantiated by the fact that the magnitude and time constant of the slow component were significantly different from zero in all three groups. The time constant and magnitude of the slow component were the same in all three groups. The parameters of the rapid component of the recovery VOWresponse were also the same in the three groups. Recovery VE and lk02 responses(Table 3). The twocomponent model fit both the VE and h02 recovery responses better than the one-component model in all three groups because the residual sum of squares was
Rapid component Time constant Magnitude Slow component Time constant Magnitude VE Rapid component Time constant Magnitude Slow component Time constant Magnitude
0.97t0.27 75k9
1.42t0.10 87t3
1.17t0.10 88&3
0.05~0.04
0.06kO.02 13t3
0.06rtO.03 12k3
3.29t1.33 68t7
0.86t0.12
1.3OkO.20 73t5
0.10t0.03 32t7
0.09t0.03
25t9
79t6 21t6
0.12kO.03 27k5
VCOZ
Rapid component Time constant 4.76t2.24 0.93kO.08 1.01~0.13 Magnitude 62t6 83t4 79k6 Slow component Time constant 0.10t0.03 0.11~0.03 0.13kO.04 Magnitude 38t6 17t4 21t6 Heart rate Rapid component Time constant 0.44kO.33 0.71t0.18 0.61t0.12 Magnitude 73t32 6Ok7 78k6 Slow component Time constant 0.0004~0.1 0.02*0.02 0.007+0.01 Magnitude 27k32 40*7 23k6 Values are means 2 SD. Units for time constants are min-‘. Magnitudes of the 2 components are expressed as percent of difference from peak exercise and preexercise rest value for that variable. Values for recovery Voz, VCO~, and VE responses were derived from analyses done on 30-s average data points as outlined in METHODS. Recovery heart rate responses were determined using heart rates recorded at the end of each minute of recovery.
reduced by 35-72% with the more complex model. The presence of two components in the recovery VE response is also supported by the fact that in all groups the time constant and magnitude of the slow component were significantly different from zero. Both the older and the young control groups had similar time constants and magnitudes of the slow and rapid components for both the VE and VCO~ recovery responses. However, the McArdle’s patients had a much more rapid first component of the recovery VE response than the other two groups. In addition, they had a time constant of the first component of their recovery ho2 response that was not different from zero. Recovery heart rate responses (Table 3). All recovery heart rate responses were also fit better by the twocomponent exponential model. The responses of the three groups were similar, characterized by a rapid component that accounted for 60-80% of the response with a half-time of l-l.5 min and a slow component with an extrapolated half-time of 76 min that accounted for the remaining 20-40% of the response. DISCUSSION
Over 50 years ago the slow component of the recovery exercise was proposed to be associated with the elevated blood lactate levels To2 response after high-intensity
EXERCISE
AND
RECOVERY
RESPONSES
that result from such exercise (15, 18, 20). However, a number of studies have questioned this hypothesis (1, 4, 7, 12, 22, 24). We have previously shown that altering exercise duration at moderate- to high-intensity work rates increased the slow component of recovery Vop and that the increase in the slow component of vo2 after exercise was in large part a function of an increase in temperature (12). Segal and Brooks (24) found that although muscle glycogen depletion decreased blood lactate levels during and after high-intensity exercise, it had no effect on the second component of the recovery Tjo2 response. Recently Roth and co-workers (22) reported that a transient occlusion of leg blood flow during submaximal cycle ergometer exercise increased blood lactate levels nearly fourfold over those in a control trial at the same exercise intensity, yet postexercise VO, was the same in both conditions. However, to date these studies have been able to bring about only a partial dissociation between blood lactate levels and the slow component of the recovery VO, responses. In the present study we were able to bring about a complete dissociation between blood lactate levels and the slow component of the recovery vo2 response after high-intensity exercise. The McArdle’s disease patients did not increase their blood lactate levels whatsoever during and after maximal exercise. However, the slow component of their recovery VO, response after maximal exercise was the same as those of the two groups of control subjects. That the three groups had the same second component of their recovery VOW response is supported by the similarity of the time constants and magnitudes attributed to it derived from the nonlinear regression analyses (Table 3). In addition, even simple inspection of Fig. 3 indicates that the relative recovery VO, responses of the McArdle’s disease patients are, at worst, the same as those of the other two groups. Also, even though blood lactate was still markedly elevated above preexercise levels after 15 min of recovery in both the young and the older control groups, their Tj02 had essentially returned to that measured at rest before exercise. Thus, becausethe patients with McArdle’s disease had the same second, slow component of their recovery VO, response after high-intensity exercise as two other groups of subjects despite dramatic differences in blood lactate levels among the groups, the second, slow component of the recovery VOW response after high-intensity exercise cannot be the result of a lactacid mechanism. This must be the case unless the McArdle’s patients have some other energy-requiring mechanism that is not operative in healthy individuals and that has the same magnitude and time course as the lactacid mechanism in healthy individuals. Two other mechanisms have been proposed to underlie the slow component of the recovery v02 response after high-intensity exercise: 1) the calorigenic effects of increased plasma catecholamine levels (7), and 2) the Q10 effect of increased muscle and body temperatures (4,12). There is little reason to expect that the responses of these two potentially calorigenic mechanisms to maximal exercise are different in the McArdle’s patients relative to healthy individuals. The similar time courses of the
OF
McARDLE’S
PATIENTS
1397
decline in recovery heart rate in the three groups in the present study may indicate a similar rate of decline in sympathetic activation in them, at least with respect to the noradrenergic nerve endings in the area of the sinoatrial node. In addition, Blomqvist and Lewis (3) have shown that these patients have a normal response to ,8adrenergic agonists and, when expressed relative to their much lower vozmax, normal catecholamine responses to progressive levels of exercise up to and including maximal exercise. Whereas muscle or body temperatures were not measured in this study, we know of no data to support the contention that they would change differently in the patients and the control subjects in the present study. During submaximal exercise the McArdle’s patients began to hyperventilate at the same relative work rate where age-matched and VO 2m,,-matched control subjects began to hyperventilate. The McArdle’s patients also continued to hyperventilate further with respect to both 0, and CO2 at higher exercise intensities. The McArdle’s patients did not increase their blood H+ levels whatsoever during exercise; rather they became alkalotic as a result of their hyperventilation without an underlying metabolic acidosis. Thus it appears either that the-a&dosis that accompanies high-intensity exercise does not elicit the hyperventilation also evident at this level of exertion or that a redundant control system exists and some other mechanism elicits the hyperventilation in the face of a lack of increase in blood H+ levels. Although it is presently not possible to discern between these two options, a number of other mechanisms, primarily neural in nature (5), have been proposed to underlie the hyperventilation of high-intensity exercise, and recently Pan and co-workers (21) have shown in ponies that the hyperventilation of high-intensity exercise is independent of arterial H+ levels. It has been proposed that the hyperventilatory response to maximal exercise in McArdle’s patients is a result of muscle pain (26). However, in the present study none of the patients perceived any apprehension or pain correlated in any way to the progressive hyperventilation that occurred during the latter stages of exercise. In fact, some of the patients experienced no muscular pain and most had no apprehension of it during exercise. This was also the case in our previous description of the ventilatory threshold in these patients (9, 10) and in another report by other investigators (13). In summary, the McArdle’s patients began to hyperventilate at the same relative work rate as the two groups of control subjects, despite the absence of an increase in blood lactate or H+ levels. Thus it appears that the hyperventilation that accompanies high-intensity exercise may be the result of some mechanism other than acidosis or CO2 flux at the lung. However, it is possible that the hyperventilation that accompanies high-intensity exercise in these patients may not be mediated by the same factors that produce the hyperventilation of high-intensity exercise in healthy individuals. The McArdle’s patients also had the same second, slow component of their recovery \jop response as the two groups of healthy control subjects, again despite the fact that they had absolutely no elevation in blood lactate levels.
1398
EXERCISE
AND
RECOVERY
RESPONSES
Thus this supposedly lactacid phenomenon must be the result of some mechanism other than an energy-requiring process related to the metabolism of the lactate usually produced during high-intensity exercise. J. M. Hagberg thanks Francis Nagle for first pointing out the potential for the McArdle’s patient model in exercise physiology research early in his graduate training program. The authors acknowledge the assistance of Jerry Dempsey, Bert Forster, and Steve Lewis in reviewing initial drafts of the manuscript. This research was supported by a grant from the Muscular Dystrophy Association. D. S. King was supported by National Institute on Aging National Research Service Award AG-00078. M. A. Rogers and W. M. Kohrt were supported by National Heart, Lung, and Blood Institute National Research Service Award HL-07456. S. L. Heller was supported by an MDA postdoctoral fellowship grant. Address for reprint requests: J. M. Hagberg, Center on Aging, Room 2304 PERH Building, University of Maryland, College Park, MD 20742-2611. Received
10 April
1989; accepted
in final
form
14 November
1989.
9. 1o. 11 l
12 * 13 ’ I4
.
l5 .
16.
REFERENCES 1. BARNARD, R. J., AND M. E. FOSS. Oxygen debt: effect of betaadrenergic blockade on the lactacid and alactacid components. J. Appl. Physiol. 27: 813-816, 1969. 2. BEAVER, W. L., K. WASSERMAN, AND B. J. WHIPP. On-line computer analysis and breath-by-breath graphical display of exercise function tests. J. Appl. Physiol. 34: 123-132, 1974. 3. BLOMQVIST, C. G., AND S. F. LEWIS. Interaction between local and neurohumoral cardiovascular control mechanisms during dynamic and static exercise. In: Sympathoadrenal System, edited by N. J. Christensen, 0. Henriksen, and N. Lassen. Copenhagen: Munksgaard, 1986, p. 188-202 4. CLAREMONT, A. C., F. J. NAGLE, W. D. REDDAN, AND G. A. BROOKS. Comparison of metabolic, temperature, heart rate, and ventilatory responses to exercise at extreme ambient temperatures. Med. Sci. Sports 7: 150-154, 1975. 5. DEMPSEY, J. A., E. H. VIDRUK, AND G. S. MITCHELL. Pulmonary control systems in exercise: update. Federation Proc. 44: 22602270,1985. 6. FORSTER, H. V., J. A. DEMPSEY, J. THOMSON, E. VIDRUK, AND G. A. DOPICO. Estimation of arterial Po2, Pco~, pH, and lactate from arterialized venous blood. J. Appl. Physiol. 32: 134-137, 1972. 7. GLADDEN, L. B., W. N. STAINSBY, AND B. R. MACINTOSH. Norepinephrine increases canine skeletal muscle VO, during recovery. Med. Sci. Sports Exercise 14: 471-476, 1982. 8. GUTMANN, I., AND A. W. WAHLEFELD. L-(+)-Lactate: determination with LDH and NAD. In: Methods of Enzymatic Analysis (2nd ed.), edited by H. U. Bergmeyer. New York: Academic, 1974, p. 1464-1468.
OF
17.
18.
19. 20.
21.
22.
23. 24.
25.
26.
McARDLE’S
PATIENTS
HAGBERG, J. M. Exercise hyperventilation in patients with McArdle’s disease: reply (Letter to the Editor). J. Appl. Physiol. 55: 1639, 1983. HAGBERG, J. M., E. F. COYLE, J. E. CARROLL, J. M. MILLER, W. H. MARTIN, AND M. H. BROOKE. Exercise hyperventilation in patients with McArdle’s disease. J. Appl. Physiol. 52: 991-994, 1982. HAGBERG, J. M., R. C. HICKSON, A. A. EHSANI, AND J. 0. HOLLOSZY. Faster adjustment to and recovery from submaximal exercise in the trained state. J. Appl. Physiol. 48: 218-224, 1980. HAGBERG, J. M., J. P. MULLIN, AN? F. J. NAGLE. Effect of work intensity and duration on recovery Vo2. J. Appl. Physiol. 48: 550554, 1980. HALLER, R. G., AND S. F. LEWIS. Abnormal ventilation during exercise in McArdle’s syndrome: modulation by substrate availability. Neurology 36: 716-719, 1983. KAISER. K. K., J. PLANER, S. L. HELLER, V. PATTERSON, AND M. H. BROOKE. The incremental forearm exercise test. Muscle Nerve 9, Suppl. 5s: 250-259,1986. KROGH, A., AND J. LINDHARD. The regulation of respiration and circulation during the initial stages of muscular work. J. Physiol. Lond. 47: 112-136, 1913. LAMARRA, N., B. J. WHIPP, S. A. WARD, AND K. WASSERMAN. Effect of interbreath fluctuations on characterizing exercise gas exchange kinetics. J. Appl. Physiol. 62: 2003-2012, 1987. LEWIS, S. F., AND R. G. HALLER. The pathophysiology of McArdle’s disease: clues to regulation in exercise and fatigue. J. Appl. Physiol. 61: 391-401, 1986. MARGARIA, R., R. H. EDWARDS, AND D. B. DILL. The possible mechanisms of contracting and paying the oxygen debt and the role of lactic acid in muscular contraction. Am. J. Physiol. 106: 689-715,1933. MCARDLE, B. Myopathy due to a defect in muscle glycogen breakdown. Clin. Sci. Lond. 10: 13-18, 1951. MEAKINS, J., AND C. N. H. LONG. Oxygen consumption, oxygen debt, and lactic acid in circulatory failure. J. Clin. Inuest. 4: 273293,1927 PAN, L. G., H. V. FORSTER, G. E. BISGARD, C. L. MURPHY, AND T. F. LOWRY. Independence of exercise hyperpnea and acidosis during high-intensity exercise in ponies. J. Appl. Physiol. 60: 10161024,1986. ROTH, D. A., W. C. STANLEY, AND G. A. BROOKS. Induced lactacidemia does not affect postexercise O2 consumption. J. Appl. Physiol. 65: 1045-1049, 1988. SAS INSTITUTE. SAS User’s Guide: Statistics, Version 5 Edition. Cary, NC: SAS Institute, 1985, p. 575-606. SEGAL, S. S., AND G. A. BROOKS. Effects of glycogen depletion and work load on postexercise O2 consumption and blood lactate. J. Appl. Physiol. 47: 514-521, 1979. WASSERMAN, K., B. J. WHIPP, S. N. KOYAL, AND W. L. BEAVER. Anaerobic threshold and respiratory gas exchange during exercise. J. Appl. Physiol. 35: 236-243, 1973. WHIPP, B. J. Exercise hyperventilation in patients with McArdle’s disease (Letter to the Editor). J. Awl. Phvsiol. 55: 1638-1639,1983.
