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Alterations in peripheral blood flow consequent to maximal exercise
Alterations
in peripheral
blood
consequent
to maximal
exercise
flow
Jack H. Wilmore, &LA. Steven M. Horvath, Ph.D.* University, Calif.
E
valuations of changes in the patterns of local blood flow in the extremities consequent to exercise have been made by several investigators. Grant’ reported that a sustained contraction of the muscles of the forearm compressed the vessels in that forearm, with the degree of compression being dependent on the strength of the contraction. Barcroft and Miller? measured the flow of blood through the calf during sustained contractions at various loads and found that the plantar-flexors of the foot were almost or quite ischemic during a strong or near-maximal contraction. Barcroft and Dornhorst3 investigated the flow through the calf during rhythmic exercise and reported that pressing a moderately weighted pedal once per second over a short period of time reduced the blood flow by 40 per cent of its normal value. Other investigators have attempted to determine the recovery blood flow patterns after different exercise stresses. Elsner and Carlson studied the responses of blood flow in the calves of trained and untrained subjects after a brief treadmill exercise at 4 m.p.h. on a 10 per cent grade for 5 minutes. They reported that the group which had undergone training experienced a more rapid recovery of blood flow after
the exercise stress, possibly indicating a decrease in the local concentration of vasodilator metabolites during recovery as a result of the training program. McArdle and Verel,5 investigating the responses of blood flow in the forearms of their subjects to different amounts of ischemic work performed at different loads indicated that blood flow responses after ischemia were linearly related not only to the duration of ischemia but to the amount of work performed, except when ischemia or work was of small magnitudes. Few investigators have attempted to measure the effects of maximal exercise on the recovery patterns of blood flow in the human extremities. The present study was designed to determine the postexercise recovery patterns of blood flow consequent to maximal exercise under conditions of either unrestricted or arrested circulation to the lower limbs during the exercise period. Method The subjects were 6 male volunteers, 18 to 30 years of age, who exhibited no physical abnormalities (Table I). Seven experiments were performed on each subject. The first three consisted of riding a bicycle ergometer to fatigue, as evidenced
From the Laboratory of Environmental Stress. University of California, Santa Barbara. This study was aided in part by the Medical Research and Development Division, Office of the Surgeon partment of the Army. Received for publication Nov. 13, 1962. *Address: Department of Physical Education, University of California, Santa Barbara, University. Calif.
3.53
General,
De-
354
Am. Heart I. Sefitember, 1963
Wilmore and Horvath
by the subject’s inability to continue the exercise pace. The next three consisted of the same exercise, but, in addition, the circulation to the lower limbs was arrested during the period of exercise. The final test, for control purposes, was conducted with the subject in the supine position, with the circulation to the lower limbs arrested for an interval of 2 minutes, the average duration of circulatory arrest during and after the ischemic exercise, in order to evaluate the extent of the hyperemic response to occlusion alone. Blood flows were measured by the venous occlusion plethysmographic method, utilizing the segmental plethysmograph, as described by Hyman and Winsor. A venous occlusion pressure of 60 mm. Hg applied directly above the knee, and an arterial occlusion pressure of 210 mm. Hg applied at the ankle were used. All determinations were taken with the subject in the supine position. After the subject had rested for 30 minutes in the recumbent position, a series of 16 consecutive determinations of blood flow was made. The average of these was taken as the individual’s resting blood flow for that particular experiment. The reproducibility of the methods employed was determined from the results of a preliminary study in which 34 consecutive determinations on the forearm were taken from each of 4 subjects. The standard error of the mean ranged from 1.68 f 0.03 to 2.55 f 0.08 ml. per 100 ml. of forearm tissue per minute (Table II). After the resting determinations were made, the subject mounted the bicycle ergometer. A 3-minute warm-up period at 600 Kg.M. per minute preceded each subject’s ride to exhaustion at 1,500 Kg.M. per minute, with both work loads being performed at 50 revolutions per minute. -4fter completion of the exercise, the subject immediately dismounted and returned to the recumbent position. Postexercise blood flows were then measured for 2 minutes at 15second intervals, starting 1 minute after exercise. In a like manner, flows were recorded consecutively for 2-minute intervals every 4 minutes, i.e., 1 to 3 minutes, 5 to 7 minutes, 9 to 11 minutes, etc., up to and including 41 to 43 minutes postexercise.
In the three tests in which circulation to the lower limbs was occluded during the exhaustive effort, a pressure of 300 mm. Hg was introduced into the two thigh cuffs, which were placed as high on the thighs as possible, at that instant at which the work load was increased from 600 to 1,500 Kg.M. per minute. No peripheral pulsations could be detected in these extremities after the application of this pressure. Electrocardiograms were recorded before exercise, at l-minute intervals during exercise and the first 10 minutes of recovery, and then at 4-minute intervals until the end of the testing period. The temperature of the skin of the calf and the temperature of the room, as measured by copper constantan thermocouples, were obtained before exercise and at 4-minute intervals after exercise. Throughout the entire study, the temperature of the room varied from 20 to 26”C., with the individual variation for any one experiment never exceeding f 1°C. Results
The mean riding time of the 6 subjects with unrestricted circulation during the exercising period was 215 seconds, compared to a mean time of 55 seconds when circulation to the lower limbs was occluded during the exercise. The temperature of the skin of one calf varied only f 1°C. during any one test. However, the temperature of the skin of the calf undergoing measurement of blood flow was always 0.2 to 1.8”C. lower than that of the other calf. At no time were abnormalities noted in the resting or exercising electrocardiograms of the 6 subjects. Only slight differences in the means for the maximum heart rates during exercise were observed between the two exercise conditions. The rates were 180 beats per minute during exercise with unrestricted circulation, and 172 beats per minute with occluded circulation. No correlation was found when the maximum heart rates were compared with the corresponding riding times. Although the resting and maximum heart rates before and during the two conditions of exercise were only slightly different, a significant difference at the 1 per cent level (t = 11.197) was noted between the individual recovery
Volume Number
66 3
Alterations
Table I. Physical
characteristics
~
P,b)
in peripheral
blood $0~ on maximal
exercise
355
of the subjects )
727
1
y;$t
/
S~r~2prea
~
Vdyw$
calf
Subject 30 25 18 21 26 27
1. 2. 3. 4. 5. 6.
Table II. Variability
183 176 188 183 180 191
86 ;: 80 73 88
2.08 1.88 2.02 2.02 1.92 2.18
1,700 1,300 960 1,520 540 1,160
of blood Jlow during a single test period Blood flow (ml./100 ml./min.)
Subject*
Limb volume (ml.1
Number determinations
of
Standard error of the mean Range
Mean
Forearm 1. 3. 7. 8.
540 500 240 200
3.5 34 34 34
1.0-2.1 2.14.3 1.9-3.3 1.0-2.4
1.7 2.6 2.6 1.8
0.03 0.08 0.07 0.06
1. 2. 3. 4. 5. 6.
1,700 1,300 960 1,520 540 1,160
16 16 16 16 16 16
0.7-1.0 1.2-2.0 l.l-1,8 0.4-0.8 1.3-2.3 0.9-l .3
0.8 1.7 1.3 0.6 1.8 1.1
0.01 0.06 0.04 0.03 0.06 0.03
Calf
*Subjects
in the supine
position.
Table III. Equations
o-f mean flow values Primary
All
subjects Occluded circulation Unrestricted circulation
Subject 1 Occluded circulation Unrestricted circulation
In y= -0.40x+ In y = -0.32x
lny= In y=
-0.57x+ -0.40x+
rates. The recovery from exercise with occluded circulation was much faster than from the exercise with unrestricted circulation. By the end of the testing period, the mean heart rate under the occluded conditions was near its mean pre-exercise
phase
+
Secondary
8.67 8.52
10.25 8.70
phase
In y= In y=
-0.06x+ -0.06x+
4.06 4.06
lny= lny=
-0.04x+ -0.14x+
3.12 5.52
resting level, differing by only 9 beats per minute. At the same time, the mean rate under unrestricted conditions was still 20 beats above its resting level (Fig. 1). A high degree of variability among individual subjects’s day-to-day resting levels
356
Am. Heart .I. S@tcmber, 1963
Wilmore and Horvath
Table IV. Calf’ blood jlow and heart rate re@onses to work* of circulation to the lower extremities during work
Heart rate (beats per min.)
Blood flow (ml./100 ml./min.) Subject
Riding time (sec.)
Test conditionst Restingj
1.
as mod$ied by the przsencl: or absence
End
test
Resting
End
Temperalure (“C.1
test 466 301 325 75 so 76
C-l c-2 c-3 o-1 o-2 o-3 R-l
0.8 0.9 0.8 0.8 1.2 1.0 0.8
6.4 10.6 13.1 9.7 9.7 14.1 3.1
1.8 0.8 1.4 0.8 1.4 1.9 0.3
64 63 60 53 64 54 63
2.
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.4 2.0 1.7 1.4 0.8 1.4 2.3
14.8 16.2 16.8 9.5 7.5 11.1 10.6
1.4 1.9 1.7 1.3 0.9 1.6 1.6
65 65 65 52 67 58 60
175 180 188 147 166 186
3.
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.6 1.4 1.3 2.7 0.9 1.0 0.9
5.7 5.1 3.8 17.5 6.5 13.1 7.3
2.2 2.0 1.5 3.5 1.1 0.9 1.0
70 62 69 59 67 60
185 178 168 186 196
4.
C-l c-2 c-3 o-1 o-2 O-3 R-l
0.4 1.0 0.6 1.0 1.3 1.1 1.0
4.3 5.6 3.8 4.6 8.9 5.5 5.1
1.3 1 3 0.9 1.2 1.7 I .2 0.5
55 68 58 79 60 65 69
178 185 186 180 180 180
72 86 90 79 65 94 61
240 237 288 63 65 75
20.5 24.2 25.5 23.0 24.6 20.8 22.0
5.
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.8 1.8 1.6 2.3 1.1 0.8 1.7
13.5 13.6 24.4 27.8 10.2 5.9 12.2
2.4 3 1 2.3 3.4 2.2 1.0 1.1
70 72 73 68 68 56 60
180 174 180 180 168 176
80
138 116 95 41 30 38
23.8 25.0 25.8 20.8 19.8 19.8 20.6
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.1 0.9 1.2 0.7 0.4 0.9 0.8
4.7 11.1 10.3 15.3 2.1 7.2 11.6
1.2 1.2 1.7 1.2 0.5 0.7 1.0
85 75 83 70 79
178 180 182 161 168 162
117 136 175 55 62 66
26.0 23.7 24.1 21 .o 20.8 20.4 20.8
6.
*Work was performed on a bicycle ergometer at 1.500 Kg.M. per minute. fC: Exercise with unrestricted flow to the lower extremities. 0: Exercise minutes of arrested circulation in the supine position. :Resting flow is the mean of at least 16 consecutive determinations.
with
175 175 150 164 171
arrested
71 75 81 47 67 77 so
278 220 320 38 27 64
20.0 23.0 20.4 24.2 23.0 21.2 22.0
125 225 163 32 37 56
86 80 83 81 79 65
Y:: 81 70 71 60 97 100 103 75 81 79 79
circulation
24.2 22.2 23.6 21.0 20.8
of the
lower
23.8 25.0 26.0 19.8 25.8
extremities.
R: Two
Volume
66
Number
3
Alterations
in peripheral
of blood flow was noted. Subject 3 showed the highest variability, ranging from 0.9 to 2.7 ml. per 100 ml. of calf tissue per minute. Subject 1 showed the least variability, ranging from 0.8 to 1.2 ml. per 100 ml. of calf tissue per minute (Table II). Peak blood flows after exercise were generally observed within the first 3 minutes of recovery. In the majority of experiments the flows had returned to their resting levels at the conclusion of the test. The mean recovery blood flow values, under both conditions of exercise, were plotted semilogarithmically. Two distinctl) separate phases of each recovery curve were observed. The initial phase was characterized by a rapid rate of descent, whereas the secondary phase showed a much more gradual slope (Fig. 2). Similar patterns were seen for each individual subject (Fig. 3). Each phase of the recovery curve represented an independent, linear relationship, indicating that both phases of each curve were exponential in nature. An analysis of each phase was made to
blood flow on maximal
exercise
357
determine their respective equations. The equations of the -mean flow values for all subjects and for an individual (Subject 1) are shown in Table I I I. No significant difference was found between the blood flow recovery curves after the two separate exercise conditions. Both curves tended to parallel each other throughout the recovery period. Patterns of blood flow during the control experiments were quite unlike those found during recovery after either of the two exercising conditions (Fig. 4). Peak flows were obtained within 15 seconds after the restoration of the occluded circulation. The flows then dropped to the resting level within 1 minute and continued to decrease, reaching a mean minimum value of 0.5 ml. below the resting level 10 minutes later. At 23 minutes postocclusion, the flows had leveled off to values within f 0.2 ml. of the resting values (Table IV). The subjects showed little reaction to the control experiments in which circulation to both legs had been occluded for a
\-\\I-‘-I.:-: 0 = Unrsstri#sd
X = Arrested
Fig. 1. The recovery pattern of the heart and without circulation to the exercising the mean values for the 6 subjects.
Circulation
C~rculol~on
rate after exhaustive exercise, with limbs. The plotted points represent
358
Am. Heart
Wilmore and Horvath
Sefitember,
J. 1963
Fig. 2. The recovery patterns of calf blood flow after exhaustive exercise, with and without circulation to the exercising limbs. The plotted points represent the mean values of each 2-minute interval for the 6 subjects.
brief Z-minute interval. More positive responses were noted both during and after the ischemic exercises. Ten to 15 seconds before the end of exercise the subjects expressed a feeling of general and complete muscular fatigue in both legs. Considerable difficulty in moving from the bicycle to the supine position was observed after the exercise. Shortly after the subject assumed the supine position, dull pain was noted in the back and lower legs. When the occluding pressures were released, the
pain disappeared, and apnea which lasted for several seconds occurred, and was followed by slow, deep breathing, and a feeling of warmth in the legs. Discussion
The subjects’ reactions to circulatory occlusion, both during and after exercise and during the 2-minute control tests, are relatively consistent with the findings of others.5v7 During the control experiments, there
Volume Number
66 3
Alterations
in peripheral
blood $0~ on maximal
exercise
Subject
I
l. . -.
359
, .
.
Arrntrd
Circulation
.. .
‘.. . ...’
Work Load .*a . . . . . . .‘:‘...,*
Timr
1500 Kg. MI Minula
for ..*.
64 -:..
.. .. .
Seconds .
...
. . . .. . - ‘.
in minutes
Fig. 3. The calf blood flow of Subject 1 after a maximal exercise to fatigue, with unrestricted and arrested lation to the lower limbs during work. The plotted points represent the mean values of three experiments and three without circulation.
circuwith
9e-
i I
,-
Reactive
Hyprrrmio
-2
Occlusion
Miub
=-, s.32-
I b
I09wWTime
Fig. 4. Reactive the mean blood
hyperemia flow values
after 2 minutes of arterial for the 6 subjects.
in minutes
occlusion
of the lower
limbs.
The plotted
points
represent
360
Wilmore and Horvath
was a short l-minute interval during which the blood flow values dropped below their resting levels. Apparently, the blood and oxygen debt incurred during the interval of anoxia had more than been repaid during the interval of reactive hyperemia. This finding is in general agreement with the results of other investigators, although the duration of the subnormal blood flow was somewhat greater in the present study.8-1o The recovery blood flow curves after the two different conditions of exercise were similar despite the reduction of the mean work capacity with occluded circulation to one third to one sixth of that with unrestricted circulation. Under the work loads of these experiments, the muscles of the legs were in a state of near-maximal contraction during the major portion of the total exercise. Consequently, the muscles during contraction were possibly restricting the blood flow to and from the legs in much the same manner that the occlusion cuffs were restricting the flow during the ischemic exercise.l-“z5 Since the blood flow responses after both exercise conditions were similar, this suggests that the muscles were working under equivalent degrees of ischemia during the latter stages of both exercises. The time differential between the two conditions of exercise needed to reach this same degree of ischemia existed primarily because in one instance (in which the esercise was performed with occluded circulation) the muscles were working completely under anaerobic conditions, whereas in the other the muscles were working under both aerobic and anaerobic conditions due to the constricting action of the contracting muscles during a near-maximal rhythmic exercise. It would appear that the fatigue experienced under both conditions of exercise was an ischemic or biochemical fatigue in the local tissues which occurred when the supply of available metabolites had been exhausted. Merton” has suggested that ischemic fatigue is biochemical in nature and is explained by the fact that, because the muscles lack oxygen, the biochemical changes underlying the contractile process of the muscles become defective. McArdle and Verel,6 analyzing the factor(s) re-
Am. Hrart J. ScfMnber, 1963
sponsible for the subject’s ability to sustain a maximal exercise to fatigue under anaerobic conditions indicated that the role of myoglobin in supplying oxygen, and the quantity of oxygen available in the volume of blood trapped in the exercising extremities, was small. They suggested that the biochemical processes concerned with the release and utilization of the energy stored in glycogen, and phosphate compounds, such as creatine phosphate, were the primary factors of importance. The occurrence of two distinct phases of each recovery curve, which has not been reported in previous investigations, may be due in part to the magnitude of the activity. Consequently, it is suggested that the appearance of these two phases is related to or was a result of the ischemic working conditions induced by the exhaustive exercise. Since the reactive hyperemic response with its increased blood flow which was observed during the resting experiments could not account for the marked increase in blood flow after exercise with occluded circulation, some other explanation must be sought. It is suggested that the initial or primary phase of the recovery curve was, in part, a function of the reactive hyperemic response caused by the ischemic conditions of exercise and, in part, as was the secondary phase, a function of the normal blood flow debt incurred consequent to exercise. Similar curves exhibiting the same twophase characteristics have been noted by other investigators in respect to the recovery oxygen debt after a maximal esercise.12z13 The first phase of this curve has generally been referred to as the alactacid portion of the oxygen debt, and the second phase as the lactacid portion. It is quite possible that a direct relationship exists between the recovery blood flow response and the oxygen debt after a masima1 exercise. Elsner and Carlson reported that, in their study of postexercise hyperemia in trained and untrained subjects, the time for recovery of blood flow was prolonged beyond the time for repayment of the oxygen debt. They also found that training reduced the recovery blood flow, whereas the oxygen debt was unaffected, which suggests that the two phenomena were unrelated. However, the exercise
TVolume 66 Number 3
Alterations
in peripheral
used in their study was not maximal, so that, consequently, their results and suggestions cannot be specifically applied to the present study.4 No direct correlation was found between the mean heart rate recovery and the mean blood flow recovery responses. During the first few minutes of recovery the heart rate decreased at a much faster rate than did the blood flow. At the completion of each experiment, however, the blood flow was approximately back to its pre-exercise resting level, whereas the heart rate was 9 to 20 beats per minute above its preexercise level. The maximum heart rates incurred during exercise were basically the same for both exercise conditions, despite the large difference in total work performed. This can be partially explained by the fact that similar degrees of ischemia occurred during the latter stages of each exercise condition, indicating that the numbers of trapped metabolites present in the working muscles were also similar. The accumulation of these trapped metabolites excited a reflex from the working muscles, resulting in an increased heart rate in both cases. This is in agreement with the conclusions of other investigators who have shown that the heart rate is controlled by impulses arising from the working muscles.‘4-16 The significant difference between the mean heart rate recovery curves after the two exercise conditions could possibly be explained on the basis of the amount of actual work performed. Brouha” reported that the speed of heart rate recovery after exercise depended on the total amount of work performed. He found that the more work an individual performed, the slower was his heart rate recovery. However, this may only partially explain these results, since the differences noted between the two curves in the present study were not so great as one might expect when one considers the respective differences in the total work completed. Summary
Recovery patterns of blood flow were studied after an exhaustive maximal exercise on a bicycle ergometer at 1,500 Kg.M. per minute under conditions of (a) unrestricted circulation, and (b) occluded
blood $0~ on maximal
exercise
361
circulation of the lower limbs. In addition, electrocardiograms were recorded before, during, and after exercise. Exercising with the circulation to the lower limbs occluded reduced the mean work capacity of each of the 6 subjects to one third to one sixth of his work capacity with unrestricted circulation. The mean maximum heart rates under both conditions were similar. The recovery of the heart rate after the exercise of shorter duration, when the circulation had been occluded, was much faster than after the longer exercise with unrestricted circulation. The mean blood flow recovery curves after both conditions of exercise indicated that (a) there was no statistical difference between the mean recovery rates after the two conditions, despite the time differential needed to reach the same level of fatigue, and (b) the recovery curves after both exercises were characterized by two distinctly different rates of recovery, which followed independent, exponentially linear equations. Although blood flow in the calf had returned to approximately its preexercise resting level by the completion of each experiment, the heart rates were still elevated 9 to 20 beats per minute above their pre-exercise level. REFERENCES 1. Grant, R. T.: Observations on the blood circulation in voluntary muscles in man, Clin. Sc. 3:157, 1938. 2. Barcroft, H., and Millen, J. L. E.: The blood flow through muscle during sustained contraction, J. Physiol. 97:17, 1939. 3. Barcroft, H., and Dornhorst, A. C.: The blood flow in the human calf during rhythmic exercise, J. Physiol. 109:402, 1949. 4. Elsner, R. W., and Carlson, L. D.: Postexercise hyperemia in trained and untrained subjects, I. ADDI. Phvsiol. 17:436. 1962. 5. McArdle, B., and Verel, D.: Responses to ischemic work in the human forearm, Clin. SC. 15:305, 1956. 6. Hyman, C., and Winsor, T.: The application of the segmental plethysmograph to the measurement of blood flow through the limbs of human beings, Am. J. Cardiol. 4:667, 1960. 7. Abramson, D. I.: Vascular responses in the extremities of man in health and disease, Chicago, 1944, Ilniversity of Chicago Press. D. I., Katzenstein, K. H., and 8. Abramson, Ferris, E. B.: Observations on reactive hyperemia in various portions of the extremities, AM. HEART I. 22:329. 1941. 9. Abramson, D. I., Katzenstein, K. H., and Ferris, E, B,: Effect of short periods of arterial
362
10.
11. 12.
13.
Am. Heart J. September, 1963
Wilmore and Horvath
occlusion on blood flow and oxygen uptake, J. Appl. Physiol. 16:851, 1961. Wilkins, R. W., and Eichna, L. W.: Blood flow to the forearm and calf: reactive hyperemia: factors influencing the blood flow during the vasodilatation following ischemia, Bull. Johns Hopkins Hosp. 68:450, 1941. Me&on, P. E.: Voluntary strength and fatigue, 1. Phvsiol. 123553. 1954. Henry, F. M., and DeMoor, J.: Lactic and alactic oxygen consumption in moderate exercise of graded intensity, J. Appl. Physiol. 8:610, 1956. Hill, A. V., Long, C. N. H., and Lupton, H.: Muscular exercise, lactic acid, and the supply and utilization of oxygen, Proc. Roy. Sot., B. %B :4.55, 1924.
14.
15.
16.
17.
Alam, M., and Smirk, F. H.: Observations in man on the pulse-accelerating reflex from the voluntary muscles of the legs, J. Physiol. 92:167, 1938. Asmussen, E., Nielson, M., and Wieth-Pederson, G.: On the regulation of circulation during muscular work, Acta physiol. scandinav. 6:353, 1943. Tuttle, W. W., and Horvath, S. M.: Comparison of effects of static and dynamic work on blood pressure and heart rate, J. Appl. Physiol. 10:294, 19.57. Rosenbaum, F. F., and Belknap, E. L., editors: Work and the heart, New York, 1959, Paul B. Hoeber, Inc.
in peripheral
blood
consequent
to maximal
exercise
flow
Jack H. Wilmore, &LA. Steven M. Horvath, Ph.D.* University, Calif.
E
valuations of changes in the patterns of local blood flow in the extremities consequent to exercise have been made by several investigators. Grant’ reported that a sustained contraction of the muscles of the forearm compressed the vessels in that forearm, with the degree of compression being dependent on the strength of the contraction. Barcroft and Miller? measured the flow of blood through the calf during sustained contractions at various loads and found that the plantar-flexors of the foot were almost or quite ischemic during a strong or near-maximal contraction. Barcroft and Dornhorst3 investigated the flow through the calf during rhythmic exercise and reported that pressing a moderately weighted pedal once per second over a short period of time reduced the blood flow by 40 per cent of its normal value. Other investigators have attempted to determine the recovery blood flow patterns after different exercise stresses. Elsner and Carlson studied the responses of blood flow in the calves of trained and untrained subjects after a brief treadmill exercise at 4 m.p.h. on a 10 per cent grade for 5 minutes. They reported that the group which had undergone training experienced a more rapid recovery of blood flow after
the exercise stress, possibly indicating a decrease in the local concentration of vasodilator metabolites during recovery as a result of the training program. McArdle and Verel,5 investigating the responses of blood flow in the forearms of their subjects to different amounts of ischemic work performed at different loads indicated that blood flow responses after ischemia were linearly related not only to the duration of ischemia but to the amount of work performed, except when ischemia or work was of small magnitudes. Few investigators have attempted to measure the effects of maximal exercise on the recovery patterns of blood flow in the human extremities. The present study was designed to determine the postexercise recovery patterns of blood flow consequent to maximal exercise under conditions of either unrestricted or arrested circulation to the lower limbs during the exercise period. Method The subjects were 6 male volunteers, 18 to 30 years of age, who exhibited no physical abnormalities (Table I). Seven experiments were performed on each subject. The first three consisted of riding a bicycle ergometer to fatigue, as evidenced
From the Laboratory of Environmental Stress. University of California, Santa Barbara. This study was aided in part by the Medical Research and Development Division, Office of the Surgeon partment of the Army. Received for publication Nov. 13, 1962. *Address: Department of Physical Education, University of California, Santa Barbara, University. Calif.
3.53
General,
De-
354
Am. Heart I. Sefitember, 1963
Wilmore and Horvath
by the subject’s inability to continue the exercise pace. The next three consisted of the same exercise, but, in addition, the circulation to the lower limbs was arrested during the period of exercise. The final test, for control purposes, was conducted with the subject in the supine position, with the circulation to the lower limbs arrested for an interval of 2 minutes, the average duration of circulatory arrest during and after the ischemic exercise, in order to evaluate the extent of the hyperemic response to occlusion alone. Blood flows were measured by the venous occlusion plethysmographic method, utilizing the segmental plethysmograph, as described by Hyman and Winsor. A venous occlusion pressure of 60 mm. Hg applied directly above the knee, and an arterial occlusion pressure of 210 mm. Hg applied at the ankle were used. All determinations were taken with the subject in the supine position. After the subject had rested for 30 minutes in the recumbent position, a series of 16 consecutive determinations of blood flow was made. The average of these was taken as the individual’s resting blood flow for that particular experiment. The reproducibility of the methods employed was determined from the results of a preliminary study in which 34 consecutive determinations on the forearm were taken from each of 4 subjects. The standard error of the mean ranged from 1.68 f 0.03 to 2.55 f 0.08 ml. per 100 ml. of forearm tissue per minute (Table II). After the resting determinations were made, the subject mounted the bicycle ergometer. A 3-minute warm-up period at 600 Kg.M. per minute preceded each subject’s ride to exhaustion at 1,500 Kg.M. per minute, with both work loads being performed at 50 revolutions per minute. -4fter completion of the exercise, the subject immediately dismounted and returned to the recumbent position. Postexercise blood flows were then measured for 2 minutes at 15second intervals, starting 1 minute after exercise. In a like manner, flows were recorded consecutively for 2-minute intervals every 4 minutes, i.e., 1 to 3 minutes, 5 to 7 minutes, 9 to 11 minutes, etc., up to and including 41 to 43 minutes postexercise.
In the three tests in which circulation to the lower limbs was occluded during the exhaustive effort, a pressure of 300 mm. Hg was introduced into the two thigh cuffs, which were placed as high on the thighs as possible, at that instant at which the work load was increased from 600 to 1,500 Kg.M. per minute. No peripheral pulsations could be detected in these extremities after the application of this pressure. Electrocardiograms were recorded before exercise, at l-minute intervals during exercise and the first 10 minutes of recovery, and then at 4-minute intervals until the end of the testing period. The temperature of the skin of the calf and the temperature of the room, as measured by copper constantan thermocouples, were obtained before exercise and at 4-minute intervals after exercise. Throughout the entire study, the temperature of the room varied from 20 to 26”C., with the individual variation for any one experiment never exceeding f 1°C. Results
The mean riding time of the 6 subjects with unrestricted circulation during the exercising period was 215 seconds, compared to a mean time of 55 seconds when circulation to the lower limbs was occluded during the exercise. The temperature of the skin of one calf varied only f 1°C. during any one test. However, the temperature of the skin of the calf undergoing measurement of blood flow was always 0.2 to 1.8”C. lower than that of the other calf. At no time were abnormalities noted in the resting or exercising electrocardiograms of the 6 subjects. Only slight differences in the means for the maximum heart rates during exercise were observed between the two exercise conditions. The rates were 180 beats per minute during exercise with unrestricted circulation, and 172 beats per minute with occluded circulation. No correlation was found when the maximum heart rates were compared with the corresponding riding times. Although the resting and maximum heart rates before and during the two conditions of exercise were only slightly different, a significant difference at the 1 per cent level (t = 11.197) was noted between the individual recovery
Volume Number
66 3
Alterations
Table I. Physical
characteristics
~
P,b)
in peripheral
blood $0~ on maximal
exercise
355
of the subjects )
727
1
y;$t
/
S~r~2prea
~
Vdyw$
calf
Subject 30 25 18 21 26 27
1. 2. 3. 4. 5. 6.
Table II. Variability
183 176 188 183 180 191
86 ;: 80 73 88
2.08 1.88 2.02 2.02 1.92 2.18
1,700 1,300 960 1,520 540 1,160
of blood Jlow during a single test period Blood flow (ml./100 ml./min.)
Subject*
Limb volume (ml.1
Number determinations
of
Standard error of the mean Range
Mean
Forearm 1. 3. 7. 8.
540 500 240 200
3.5 34 34 34
1.0-2.1 2.14.3 1.9-3.3 1.0-2.4
1.7 2.6 2.6 1.8
0.03 0.08 0.07 0.06
1. 2. 3. 4. 5. 6.
1,700 1,300 960 1,520 540 1,160
16 16 16 16 16 16
0.7-1.0 1.2-2.0 l.l-1,8 0.4-0.8 1.3-2.3 0.9-l .3
0.8 1.7 1.3 0.6 1.8 1.1
0.01 0.06 0.04 0.03 0.06 0.03
Calf
*Subjects
in the supine
position.
Table III. Equations
o-f mean flow values Primary
All
subjects Occluded circulation Unrestricted circulation
Subject 1 Occluded circulation Unrestricted circulation
In y= -0.40x+ In y = -0.32x
lny= In y=
-0.57x+ -0.40x+
rates. The recovery from exercise with occluded circulation was much faster than from the exercise with unrestricted circulation. By the end of the testing period, the mean heart rate under the occluded conditions was near its mean pre-exercise
phase
+
Secondary
8.67 8.52
10.25 8.70
phase
In y= In y=
-0.06x+ -0.06x+
4.06 4.06
lny= lny=
-0.04x+ -0.14x+
3.12 5.52
resting level, differing by only 9 beats per minute. At the same time, the mean rate under unrestricted conditions was still 20 beats above its resting level (Fig. 1). A high degree of variability among individual subjects’s day-to-day resting levels
356
Am. Heart .I. S@tcmber, 1963
Wilmore and Horvath
Table IV. Calf’ blood jlow and heart rate re@onses to work* of circulation to the lower extremities during work
Heart rate (beats per min.)
Blood flow (ml./100 ml./min.) Subject
Riding time (sec.)
Test conditionst Restingj
1.
as mod$ied by the przsencl: or absence
End
test
Resting
End
Temperalure (“C.1
test 466 301 325 75 so 76
C-l c-2 c-3 o-1 o-2 o-3 R-l
0.8 0.9 0.8 0.8 1.2 1.0 0.8
6.4 10.6 13.1 9.7 9.7 14.1 3.1
1.8 0.8 1.4 0.8 1.4 1.9 0.3
64 63 60 53 64 54 63
2.
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.4 2.0 1.7 1.4 0.8 1.4 2.3
14.8 16.2 16.8 9.5 7.5 11.1 10.6
1.4 1.9 1.7 1.3 0.9 1.6 1.6
65 65 65 52 67 58 60
175 180 188 147 166 186
3.
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.6 1.4 1.3 2.7 0.9 1.0 0.9
5.7 5.1 3.8 17.5 6.5 13.1 7.3
2.2 2.0 1.5 3.5 1.1 0.9 1.0
70 62 69 59 67 60
185 178 168 186 196
4.
C-l c-2 c-3 o-1 o-2 O-3 R-l
0.4 1.0 0.6 1.0 1.3 1.1 1.0
4.3 5.6 3.8 4.6 8.9 5.5 5.1
1.3 1 3 0.9 1.2 1.7 I .2 0.5
55 68 58 79 60 65 69
178 185 186 180 180 180
72 86 90 79 65 94 61
240 237 288 63 65 75
20.5 24.2 25.5 23.0 24.6 20.8 22.0
5.
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.8 1.8 1.6 2.3 1.1 0.8 1.7
13.5 13.6 24.4 27.8 10.2 5.9 12.2
2.4 3 1 2.3 3.4 2.2 1.0 1.1
70 72 73 68 68 56 60
180 174 180 180 168 176
80
138 116 95 41 30 38
23.8 25.0 25.8 20.8 19.8 19.8 20.6
C-l c-2 c-3 o-1 o-2 o-3 R-l
1.1 0.9 1.2 0.7 0.4 0.9 0.8
4.7 11.1 10.3 15.3 2.1 7.2 11.6
1.2 1.2 1.7 1.2 0.5 0.7 1.0
85 75 83 70 79
178 180 182 161 168 162
117 136 175 55 62 66
26.0 23.7 24.1 21 .o 20.8 20.4 20.8
6.
*Work was performed on a bicycle ergometer at 1.500 Kg.M. per minute. fC: Exercise with unrestricted flow to the lower extremities. 0: Exercise minutes of arrested circulation in the supine position. :Resting flow is the mean of at least 16 consecutive determinations.
with
175 175 150 164 171
arrested
71 75 81 47 67 77 so
278 220 320 38 27 64
20.0 23.0 20.4 24.2 23.0 21.2 22.0
125 225 163 32 37 56
86 80 83 81 79 65
Y:: 81 70 71 60 97 100 103 75 81 79 79
circulation
24.2 22.2 23.6 21.0 20.8
of the
lower
23.8 25.0 26.0 19.8 25.8
extremities.
R: Two
Volume
66
Number
3
Alterations
in peripheral
of blood flow was noted. Subject 3 showed the highest variability, ranging from 0.9 to 2.7 ml. per 100 ml. of calf tissue per minute. Subject 1 showed the least variability, ranging from 0.8 to 1.2 ml. per 100 ml. of calf tissue per minute (Table II). Peak blood flows after exercise were generally observed within the first 3 minutes of recovery. In the majority of experiments the flows had returned to their resting levels at the conclusion of the test. The mean recovery blood flow values, under both conditions of exercise, were plotted semilogarithmically. Two distinctl) separate phases of each recovery curve were observed. The initial phase was characterized by a rapid rate of descent, whereas the secondary phase showed a much more gradual slope (Fig. 2). Similar patterns were seen for each individual subject (Fig. 3). Each phase of the recovery curve represented an independent, linear relationship, indicating that both phases of each curve were exponential in nature. An analysis of each phase was made to
blood flow on maximal
exercise
357
determine their respective equations. The equations of the -mean flow values for all subjects and for an individual (Subject 1) are shown in Table I I I. No significant difference was found between the blood flow recovery curves after the two separate exercise conditions. Both curves tended to parallel each other throughout the recovery period. Patterns of blood flow during the control experiments were quite unlike those found during recovery after either of the two exercising conditions (Fig. 4). Peak flows were obtained within 15 seconds after the restoration of the occluded circulation. The flows then dropped to the resting level within 1 minute and continued to decrease, reaching a mean minimum value of 0.5 ml. below the resting level 10 minutes later. At 23 minutes postocclusion, the flows had leveled off to values within f 0.2 ml. of the resting values (Table IV). The subjects showed little reaction to the control experiments in which circulation to both legs had been occluded for a
\-\\I-‘-I.:-: 0 = Unrsstri#sd
X = Arrested
Fig. 1. The recovery pattern of the heart and without circulation to the exercising the mean values for the 6 subjects.
Circulation
C~rculol~on
rate after exhaustive exercise, with limbs. The plotted points represent
358
Am. Heart
Wilmore and Horvath
Sefitember,
J. 1963
Fig. 2. The recovery patterns of calf blood flow after exhaustive exercise, with and without circulation to the exercising limbs. The plotted points represent the mean values of each 2-minute interval for the 6 subjects.
brief Z-minute interval. More positive responses were noted both during and after the ischemic exercises. Ten to 15 seconds before the end of exercise the subjects expressed a feeling of general and complete muscular fatigue in both legs. Considerable difficulty in moving from the bicycle to the supine position was observed after the exercise. Shortly after the subject assumed the supine position, dull pain was noted in the back and lower legs. When the occluding pressures were released, the
pain disappeared, and apnea which lasted for several seconds occurred, and was followed by slow, deep breathing, and a feeling of warmth in the legs. Discussion
The subjects’ reactions to circulatory occlusion, both during and after exercise and during the 2-minute control tests, are relatively consistent with the findings of others.5v7 During the control experiments, there
Volume Number
66 3
Alterations
in peripheral
blood $0~ on maximal
exercise
Subject
I
l. . -.
359
, .
.
Arrntrd
Circulation
.. .
‘.. . ...’
Work Load .*a . . . . . . .‘:‘...,*
Timr
1500 Kg. MI Minula
for ..*.
64 -:..
.. .. .
Seconds .
...
. . . .. . - ‘.
in minutes
Fig. 3. The calf blood flow of Subject 1 after a maximal exercise to fatigue, with unrestricted and arrested lation to the lower limbs during work. The plotted points represent the mean values of three experiments and three without circulation.
circuwith
9e-
i I
,-
Reactive
Hyprrrmio
-2
Occlusion
Miub
=-, s.32-
I b
I09wWTime
Fig. 4. Reactive the mean blood
hyperemia flow values
after 2 minutes of arterial for the 6 subjects.
in minutes
occlusion
of the lower
limbs.
The plotted
points
represent
360
Wilmore and Horvath
was a short l-minute interval during which the blood flow values dropped below their resting levels. Apparently, the blood and oxygen debt incurred during the interval of anoxia had more than been repaid during the interval of reactive hyperemia. This finding is in general agreement with the results of other investigators, although the duration of the subnormal blood flow was somewhat greater in the present study.8-1o The recovery blood flow curves after the two different conditions of exercise were similar despite the reduction of the mean work capacity with occluded circulation to one third to one sixth of that with unrestricted circulation. Under the work loads of these experiments, the muscles of the legs were in a state of near-maximal contraction during the major portion of the total exercise. Consequently, the muscles during contraction were possibly restricting the blood flow to and from the legs in much the same manner that the occlusion cuffs were restricting the flow during the ischemic exercise.l-“z5 Since the blood flow responses after both exercise conditions were similar, this suggests that the muscles were working under equivalent degrees of ischemia during the latter stages of both exercises. The time differential between the two conditions of exercise needed to reach this same degree of ischemia existed primarily because in one instance (in which the esercise was performed with occluded circulation) the muscles were working completely under anaerobic conditions, whereas in the other the muscles were working under both aerobic and anaerobic conditions due to the constricting action of the contracting muscles during a near-maximal rhythmic exercise. It would appear that the fatigue experienced under both conditions of exercise was an ischemic or biochemical fatigue in the local tissues which occurred when the supply of available metabolites had been exhausted. Merton” has suggested that ischemic fatigue is biochemical in nature and is explained by the fact that, because the muscles lack oxygen, the biochemical changes underlying the contractile process of the muscles become defective. McArdle and Verel,6 analyzing the factor(s) re-
Am. Hrart J. ScfMnber, 1963
sponsible for the subject’s ability to sustain a maximal exercise to fatigue under anaerobic conditions indicated that the role of myoglobin in supplying oxygen, and the quantity of oxygen available in the volume of blood trapped in the exercising extremities, was small. They suggested that the biochemical processes concerned with the release and utilization of the energy stored in glycogen, and phosphate compounds, such as creatine phosphate, were the primary factors of importance. The occurrence of two distinct phases of each recovery curve, which has not been reported in previous investigations, may be due in part to the magnitude of the activity. Consequently, it is suggested that the appearance of these two phases is related to or was a result of the ischemic working conditions induced by the exhaustive exercise. Since the reactive hyperemic response with its increased blood flow which was observed during the resting experiments could not account for the marked increase in blood flow after exercise with occluded circulation, some other explanation must be sought. It is suggested that the initial or primary phase of the recovery curve was, in part, a function of the reactive hyperemic response caused by the ischemic conditions of exercise and, in part, as was the secondary phase, a function of the normal blood flow debt incurred consequent to exercise. Similar curves exhibiting the same twophase characteristics have been noted by other investigators in respect to the recovery oxygen debt after a maximal esercise.12z13 The first phase of this curve has generally been referred to as the alactacid portion of the oxygen debt, and the second phase as the lactacid portion. It is quite possible that a direct relationship exists between the recovery blood flow response and the oxygen debt after a masima1 exercise. Elsner and Carlson reported that, in their study of postexercise hyperemia in trained and untrained subjects, the time for recovery of blood flow was prolonged beyond the time for repayment of the oxygen debt. They also found that training reduced the recovery blood flow, whereas the oxygen debt was unaffected, which suggests that the two phenomena were unrelated. However, the exercise
TVolume 66 Number 3
Alterations
in peripheral
used in their study was not maximal, so that, consequently, their results and suggestions cannot be specifically applied to the present study.4 No direct correlation was found between the mean heart rate recovery and the mean blood flow recovery responses. During the first few minutes of recovery the heart rate decreased at a much faster rate than did the blood flow. At the completion of each experiment, however, the blood flow was approximately back to its pre-exercise resting level, whereas the heart rate was 9 to 20 beats per minute above its preexercise level. The maximum heart rates incurred during exercise were basically the same for both exercise conditions, despite the large difference in total work performed. This can be partially explained by the fact that similar degrees of ischemia occurred during the latter stages of each exercise condition, indicating that the numbers of trapped metabolites present in the working muscles were also similar. The accumulation of these trapped metabolites excited a reflex from the working muscles, resulting in an increased heart rate in both cases. This is in agreement with the conclusions of other investigators who have shown that the heart rate is controlled by impulses arising from the working muscles.‘4-16 The significant difference between the mean heart rate recovery curves after the two exercise conditions could possibly be explained on the basis of the amount of actual work performed. Brouha” reported that the speed of heart rate recovery after exercise depended on the total amount of work performed. He found that the more work an individual performed, the slower was his heart rate recovery. However, this may only partially explain these results, since the differences noted between the two curves in the present study were not so great as one might expect when one considers the respective differences in the total work completed. Summary
Recovery patterns of blood flow were studied after an exhaustive maximal exercise on a bicycle ergometer at 1,500 Kg.M. per minute under conditions of (a) unrestricted circulation, and (b) occluded
blood $0~ on maximal
exercise
361
circulation of the lower limbs. In addition, electrocardiograms were recorded before, during, and after exercise. Exercising with the circulation to the lower limbs occluded reduced the mean work capacity of each of the 6 subjects to one third to one sixth of his work capacity with unrestricted circulation. The mean maximum heart rates under both conditions were similar. The recovery of the heart rate after the exercise of shorter duration, when the circulation had been occluded, was much faster than after the longer exercise with unrestricted circulation. The mean blood flow recovery curves after both conditions of exercise indicated that (a) there was no statistical difference between the mean recovery rates after the two conditions, despite the time differential needed to reach the same level of fatigue, and (b) the recovery curves after both exercises were characterized by two distinctly different rates of recovery, which followed independent, exponentially linear equations. Although blood flow in the calf had returned to approximately its preexercise resting level by the completion of each experiment, the heart rates were still elevated 9 to 20 beats per minute above their pre-exercise level. REFERENCES 1. Grant, R. T.: Observations on the blood circulation in voluntary muscles in man, Clin. Sc. 3:157, 1938. 2. Barcroft, H., and Millen, J. L. E.: The blood flow through muscle during sustained contraction, J. Physiol. 97:17, 1939. 3. Barcroft, H., and Dornhorst, A. C.: The blood flow in the human calf during rhythmic exercise, J. Physiol. 109:402, 1949. 4. Elsner, R. W., and Carlson, L. D.: Postexercise hyperemia in trained and untrained subjects, I. ADDI. Phvsiol. 17:436. 1962. 5. McArdle, B., and Verel, D.: Responses to ischemic work in the human forearm, Clin. SC. 15:305, 1956. 6. Hyman, C., and Winsor, T.: The application of the segmental plethysmograph to the measurement of blood flow through the limbs of human beings, Am. J. Cardiol. 4:667, 1960. 7. Abramson, D. I.: Vascular responses in the extremities of man in health and disease, Chicago, 1944, Ilniversity of Chicago Press. D. I., Katzenstein, K. H., and 8. Abramson, Ferris, E. B.: Observations on reactive hyperemia in various portions of the extremities, AM. HEART I. 22:329. 1941. 9. Abramson, D. I., Katzenstein, K. H., and Ferris, E, B,: Effect of short periods of arterial
362
10.
11. 12.
13.
Am. Heart J. September, 1963
Wilmore and Horvath
occlusion on blood flow and oxygen uptake, J. Appl. Physiol. 16:851, 1961. Wilkins, R. W., and Eichna, L. W.: Blood flow to the forearm and calf: reactive hyperemia: factors influencing the blood flow during the vasodilatation following ischemia, Bull. Johns Hopkins Hosp. 68:450, 1941. Me&on, P. E.: Voluntary strength and fatigue, 1. Phvsiol. 123553. 1954. Henry, F. M., and DeMoor, J.: Lactic and alactic oxygen consumption in moderate exercise of graded intensity, J. Appl. Physiol. 8:610, 1956. Hill, A. V., Long, C. N. H., and Lupton, H.: Muscular exercise, lactic acid, and the supply and utilization of oxygen, Proc. Roy. Sot., B. %B :4.55, 1924.
14.
15.
16.
17.
Alam, M., and Smirk, F. H.: Observations in man on the pulse-accelerating reflex from the voluntary muscles of the legs, J. Physiol. 92:167, 1938. Asmussen, E., Nielson, M., and Wieth-Pederson, G.: On the regulation of circulation during muscular work, Acta physiol. scandinav. 6:353, 1943. Tuttle, W. W., and Horvath, S. M.: Comparison of effects of static and dynamic work on blood pressure and heart rate, J. Appl. Physiol. 10:294, 19.57. Rosenbaum, F. F., and Belknap, E. L., editors: Work and the heart, New York, 1959, Paul B. Hoeber, Inc.