Comparison Between Reactive and Exercise Hyperemia in Normal Subjects and Patients With Peripheral Arterial Disease V.
Bartoli, M.D., F.I.C.A., and B. Dorigo, FLORENCE,
M.D.
ITALY
The hyperemia that follows a period of circulatory arrest or muscular exercise has been extensively studied both in isolated skeletal muscles of animals and in the limbs of man.1-6 More recently, attention has been focused on the mechanisms of the hyperemic reaction and local vasodilator metabolites.’-13 However, few investigations deal with the comparison between exercise and reactive hyperemia. In the limbs of healthy man and in animals, postischemic and postexercise hyperemias demonstrate similarities. The first and peak flows do not differ significantly.’4-16 The recovery time of basal flow is prolonged, especially after heavy exercise.17,18 There are only few reports of the behavior of both hyperemias in peripheral arterial disease (PAD).19-21 To our knowledge, there has been no direct comparison of the two types of hyperemia within the same group of patients. Furthermore, it should be stressed that the evaluation of muscular exercise by means of a foot ergometer is imprecise, unless supplemented by an electronic instrument that gives a direct reading of the work performed.22 Materials and Methods
Calf blood flow was measured by means of a waterfilled venous occlusion plethysmograph in 15 normal male volunteers and in 16 male patients with PAD. In the 15 apparently normal volunteers, 10 limbs from different subjects were used in each group. In the patient group the main symptom was intermittent claudication in all the limbs, with the exception of four in which rest pain and impending gangrene were present. Main arterial obstruction was localized in the terminal aorta and/or the common iliac artery in 6 patients, in the external iliac and/or the femoral artery in 7 and at the femoropopliteal level in 3. There were nine bilateral arterial obstructions. A total of 25 limbs were examined. Plethysmographic measurements were made on all subjects at rest and From the Istituto di
Patologia Medica B, University
of Florence,
Florence, Italy.
40
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
41
during reactive and exercise hyperemia. Reactive hyperemia was produced by a 5-minute application of an occlusion cuff on the thigh. Exercise was performed in the supine position by means of a specialized electronic foot ergometer.22 In normal subjects exercise was stopped when the work load was 30 and 50 kg respectively, after 115 ~ 10 sec and 135 ~ 10 sec. In patients with PAD, exercise was interrupted when the subject experienced pain. The work load range was 17-75 kg (mean 35.3 kg): 25-35 kg (12 limbs), 45-55 kg (5 limbs), less than 25 kg (6 limbs), and more than 55 kg (2 limbs). The following variables were recorded routinely in all the subjects: (1) rest or basal flow, i.e., the calf blood flow at rest; (2) first flow, i.e., the first measured hyperemic blood flow in the calf after ischemia or exercise; (3) peak flow, i.e., the maximum blood flow recorded during hyperemia; (4) time of peak flow, i.e., the time in seconds when the maximum blood flow was recorded; and (5) time course for recovery of basal flow, i.e., the duration of the hyperemia. The significance of mean differences in quantifiable variables among groups was determined by application of the student t test. The r coefficient was used to correlate variables within the
same
group.
Resul ts
.
Table 1 shows the values of basal and hyperemic blood flows and the time for the recovery of basal flow in healthy subjects. First flow and peak flow coincide. There is no significant difference in the peak flow after 5-minute ischemia or exercise with a load of 50 kg. The duration of hyperemia is significantly longer after exercise (P < .001). When the muscular load is 30 kg, the first and peak flows of exercise hyperemia are lower than in reactive hyperemia (P < .001). The time course for recovery of basal flow is similar. Table 2 shows the behavior of reactive and exercise hyperemia with variable work loads until the occurrence of pain in 25 limbs of 16 subjects with PAD. First flow, peak flow and duration of hyperemia are significantly higher after exercise than after ischemia (P < .001). Similar results (Tables 3 and 4) are course
TABLE 1 Mean Values
of Reactive and
Exercise
Hyperemia
in 10 Limbs
from
I S Normal
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
Subjects
42 TABLE 2 Mean Values
of Reactive and Exercise
Hyperemia
in 25 Limbs
from
16 Patients with PAD
obtained when the comparison of the hyperemias is made in relation to the work load. Only the peak flow of exercise hyperemia with a work load of 25-35 kg does not differ from that of reactive hyperemia (Table 3). No correlation between first flow and peak flow can be demonstrated by using the r coefficient on the values found in PAD. There is positive correlation between the time of peak flow and duration of hyperemia (Table 2). The typical course of reactive and exercise hyperemia in normals and in subjects with PAD is shown in Figures 1 and 2. The duration and excess blood flow in the calf increase much more after exercise than after ischemia. Discussion
The results of this study provide further evidence that in healthy subjects the only difference between exercise and reactive hyperemia is in the duration of recovery time for basal flow, when the muscular work load is 50 kg. Therefore, in normal limbs, maximum hyperemic flow can be evoked either by a fiveminute ischemia or by muscular work of 50 kg. The longer duration of exercise hyperemia can be attributed to a greater release and concentration of vasodilating substances in tissue fluids. Our data also demonstrate that reactive and exercise hyperemia differ significantly when arterial obstruction is present, as in arteriosclerosis obliterans of TABLE 3
Comparison
Between Mean Values
of Reactive and Exercise Hyperemia With PA D
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
in 12 Limbs From 11 Patients
43 TABLE 4
Comparison
Between Mean Values
of Reactive and Exercise Hyperemia in 5 Limbs From 4
Patients With PAD
the lower limbs. First flow and peak flow are higher and recovery time more prolonged after exercise. No correlation is demonstrable between the two hyperemic flows. These findings could be interpreted to mean that in PAD the two hyperemias are independent both in mechanism and expression. It is likely that the muscular work, when protracted until pain occurs, as in this study, produces in the calf muscles a metabolic and circulatory adjustment other than that of ischemia. This different behavior of reactive and exercise hyperemia in PAD can be explained without postulating different local metabolites or nervous mechanisms of a special kind. It is well established that the hyperemic reaction is a locally mediated phenomenon.6,15,23 It is possible that a myogenic mechanism, as stressed by Bayliss and Folkow,24,25 is present in both hyperemias, even though the initiating changes are different. 26-28 The distribution of the hyperemia is broadly similar, because in periods of ischemia of five minutes or less the contribution of the skin is quite small.17 Two metabolic hypotheses can be postulated: (1) release in the calf muscles, upon the occurrence of pain, of a substance or substances that do not appear in reactive hyperemia; (2) greater concentration of the same metabolites and possible interaction between them. Many substances can be involved in exercise and reactive hyperemia, but only a few have been identified .6 Their concentration in tissue fluids surrounding resistance vessels produces a change in the vascular tone of small arteries, arterioles, and metarterioles, allowing a blood flow adjustment. The purpose of the hyperemic reaction and the mechanism responsible for its decrease is still not clear. The metabolites can be destroyed locally, washed away, or facilitate their entry into cells to restore normal concentration.18 No close relationship can be demonstrated between hyperemic reaction and blood-debt repayment, as suggested by the classic experiment of Blair et al. 21 At present, there is no positive evidence that the metabolites are different in reactive and exercise hyperemia. It may be that their release is greater and that the magnitude and the time course of their concentration in interstitial fluids are greater after muscular exercise than after ischemia. It follows that the changes in osmolality, pH, and 02 uptake show a similar course.
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
44
FIG. 1.
Typical course of reactive and exercise hyperemia (work load 30 and 50 kg) in normal subjects.
On the other hand, we must consider the different behavior of muscular vessels in reactive and exercise hyperemia. In working hyperemia, dilation occurs not only in the vessels of active units, but also in all the vessels of the whole muscle proportional to the frequency of impulses and number of contracting units. The lasting of the postcontraction hyperemia increases as a linear function of peak blood flow.3° There is also experimental evidence that the
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
45
FIG. 2.
Typical
course
of reactive and exercise
hyperemia
in
patients
with
peripheral
arterial disease.
increase of flow in previously open capillaries is the primary source of reactive hyperemia31 and the opening of new vessels of exercise hyperemia.30 The mechanical effect of muscular contraction on calf blood flow, which is present during exercise and absent during ischemia, should be stressed. Since muscle tissue is enclosed by a tight fascia, contractions will produce an increase in tissue pressure, which in turn will have a double effect on the blood circulation in the calf. Arterial inflow will be temporarily impeded because of a &dquo;nipping&dquo; effect on the arteries, and venous outflow will be enhanced because of a compression on the venous wall.32 It follows that in muscular relaxation the venous pressure is markedly reduced, and this lowering raises the effective arterial perfusion pressure.
Summary Reactive and exercise hyperemia were compared in healthy men and in patients with PAD. In both patients and normals the calf blood flow of reactive
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
46
recorded after a 5-minute ischemia. Exercise hyperemia was measured in normals after variable work loads (30 and 50 kg) and immediately after the occurrence of pain in patients with PAD. In healthy limbs the first and peak flows of exercise and reactive hyperemia are similar. The recovery time for basal flow is prolonged after exercise. However, reactive and exercise hyperemia differ significantly when arterial obstruction due to arteriosclerosis obliterans is present. First flow and peak flow are higher and recovery time more prolonged after exercise. It is also likely that the control mechanisms of the two hyperemic reactions are different. Muscular exercise, when protracted until pain occurs, can produce a metabolic and circulatory adjustment other than that of ischemia. There is experimental evidence to support this hypothesis.
hyperemia
was
Vittorio Bartoli, M.D., F.I.C.A. Via Mannelli, 203 50132 Florence, Italy
References 1.
2.
3. 4.
5.
6. 7.
8.
9.
10.
11.
12.
creases
Barcroft, H.: Circulation in skeletal muscle, in Handbook of Physiology. Section 2: Circulation. Vol. II. Washington, American Physiology Society, 1963, p. 1353. Shepherd, J. T.: Physiology of the Circulation in Human Limbs in Health and Disease. Philadelphia, W. B. Saunders, 1963, p. 127. Chapman, C. B. (ed.): Physiology of Muscular Exercise. Circ. Res., 20: Suppl. 1, 1967. Whelan, R. F.: Control of the Peripheral Circulation in Man. Springfield, Charles C. Thomas, 1967. Strandness, D. E., Jr.: Peripheral Arterial Disease. A Physiologic Approach. London, J. & A. Churchill, 1969. Zelis, R. (ed.): The Peripheral Circulations. New York, Grune & Stratton, 1975. Rodbard, S (ed.): Local Regulation of Blood Flow, Circ. Res., 28: Suppl. 1, 1971. Tominaga, S.: Local regulation of blood flow in the skeletal muscle: Probable participation of adenosine. Scand. J. Clin. Lab. Invest., 29: 129, 1972. Hilton, S. M.: Evidence for inorganic phosphate as the initiator of post-contraction hyperaemia in skeletal muscle. Scand. J. Clin. Lab. Invest., 29: 135, 1972. Mellander S.: Tissue osmolality as a mediator of exercise hyperemia. Scand. J. Clin. Lab. Invest., 29: 139, 1972. Eklund, B.: Influence of work duration on the regulation of muscle blood flow. Acta Physiol. Scand., Suppl. 411, 1974. Järhult, J., Hillman, J., Mellander, S.: Circulatory effects evoked by "physiological" in-
of arterial
osmolality.
Acta
Physiol.
Scand., 93: 129, 1975. 13. Haddy, F. J., Scott, J. B.; Metabolic factors in peripheral circulatory regulation. Fed. Proc., 34: 2006, 1975. 14. Eichna, L. W., Wilkins, R. W.: Reactive hy-
peremia : Factors influencing the blood flow during the vasodilatation following ischaemia. Bull. Johns Hopkins Hosp., 68: 450, 1941. 15.
Dornhorst, A. C., Whelan, R. F.: The blood
flow in muscle following exercise and circulatory arrest: The influence of reduction in effective local blood pressure, of arterial hypoxia and of adrenaline. Clin. Sci., 12: 33, 1953. 16. Hilton, S. M.: Experiments on the post-contraction hyperaemia of skeletal muscle. J. Physiol. (Lond.), 120: 230, 1953. 17. Dornhorst, A. C.: Hyperaemia induced by exercise and ischaemia. Br. Med. Bull., 19:
137, 1963. W. H.: Nature and mechanism of the restoration of normal blood flow after exercise and ischemia, in Circulation in Skeletal Muscle. Edited by O. Hudlickà. Oxford, Pergamon Press, 1968, p. 205. 19. Allwood, M. J.: Redistribution of blood flow in limbs with obstruction of a main artery. Clin. Sci., 22: 279, 1962. 20. Strandell, T., Wahren, J.: Circulation in the calf at rest, after arterial occlusion and after exercise in normal subjects and in patients with intermittent claudication. Acta Med. Scand., 173: 99, 1963. 21. Hillestad, L. K.: The peripheral blood flow in 18.
Hyman, C., Wong,
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
47 intermittent claudication. VI. Plethysmographic studies. The blood flow response to exer22.
23.
24.
25.
26.
27.
cise with arrested and free circulation. Acta Med. Scand., 174: 671, 1963. Pirri, F., Zanini, A., Dorigo, B., et al.: A new electronic foot ergometer for direct reading of muscle work load. Angiology, 28: 770, 1977. Bevegard, B. S., Shepherd, J. T.: Regulation of the circulation during exercise in man. Physiol. Rev., 47: 178, 1967. Bayliss, W. M.: On the local reactions of the arterial wall to changes of internal pressure. J. Physiol. (Lond.), 28: 220, 1902. Folkow, B.: Description of the myogenic hypothesis. Circ. Res., 14-15: Suppl. 1, 279, 1964. Arai, M., Endoh, H.: Blood flow through human skeletal muscle during and after contraction. Tohoku J. Exp. Med., 114: 379, 1974. Owen, T. L., Ehrhart, I. C., Scott, J. B., et al.: A comparison of recovery times from exercise
28.
29.
30.
31.
32.
and ischemic dilations at constant pressure and flow. Proc. Soc. Exp. Biol. Med., 149: 1040, 1975. Haddy, F. J., Scott, J. B.: Metabolic factors in peripheral circulatory regulation. Fed. Proc., 34: 2006, 1975. Blair, D. A., Glover, W. E., Roddie, I. C.: The abolition of reactive and post-exercise hyperaemia in the forearm by temporary restriction of arterial inflow. J. Physiol. (Lond.), 148: 648, 1959. Khayutin, V. M.: Determinants of working hyperaemia in skeletal muscle, in Circulation in Skeletal Muscle. Edited by O. Hudlickà. Oxford, Pergamon Press, 1968, p. 145. Burton, K. S., Johnson, P. S.: Reactive hyperemia in individual capillaries of skeletal muscle. Am. J. Physiol., 223: 517, 1972. Folkow, B., Gaskell, P., Waaler, B. A.: Blood flow through limb muscles during heavy rhythmic exercise. Acta Physiol. Scand., 80: 61, 1970.
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
Bartoli, M.D., F.I.C.A., and B. Dorigo, FLORENCE,
M.D.
ITALY
The hyperemia that follows a period of circulatory arrest or muscular exercise has been extensively studied both in isolated skeletal muscles of animals and in the limbs of man.1-6 More recently, attention has been focused on the mechanisms of the hyperemic reaction and local vasodilator metabolites.’-13 However, few investigations deal with the comparison between exercise and reactive hyperemia. In the limbs of healthy man and in animals, postischemic and postexercise hyperemias demonstrate similarities. The first and peak flows do not differ significantly.’4-16 The recovery time of basal flow is prolonged, especially after heavy exercise.17,18 There are only few reports of the behavior of both hyperemias in peripheral arterial disease (PAD).19-21 To our knowledge, there has been no direct comparison of the two types of hyperemia within the same group of patients. Furthermore, it should be stressed that the evaluation of muscular exercise by means of a foot ergometer is imprecise, unless supplemented by an electronic instrument that gives a direct reading of the work performed.22 Materials and Methods
Calf blood flow was measured by means of a waterfilled venous occlusion plethysmograph in 15 normal male volunteers and in 16 male patients with PAD. In the 15 apparently normal volunteers, 10 limbs from different subjects were used in each group. In the patient group the main symptom was intermittent claudication in all the limbs, with the exception of four in which rest pain and impending gangrene were present. Main arterial obstruction was localized in the terminal aorta and/or the common iliac artery in 6 patients, in the external iliac and/or the femoral artery in 7 and at the femoropopliteal level in 3. There were nine bilateral arterial obstructions. A total of 25 limbs were examined. Plethysmographic measurements were made on all subjects at rest and From the Istituto di
Patologia Medica B, University
of Florence,
Florence, Italy.
40
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
41
during reactive and exercise hyperemia. Reactive hyperemia was produced by a 5-minute application of an occlusion cuff on the thigh. Exercise was performed in the supine position by means of a specialized electronic foot ergometer.22 In normal subjects exercise was stopped when the work load was 30 and 50 kg respectively, after 115 ~ 10 sec and 135 ~ 10 sec. In patients with PAD, exercise was interrupted when the subject experienced pain. The work load range was 17-75 kg (mean 35.3 kg): 25-35 kg (12 limbs), 45-55 kg (5 limbs), less than 25 kg (6 limbs), and more than 55 kg (2 limbs). The following variables were recorded routinely in all the subjects: (1) rest or basal flow, i.e., the calf blood flow at rest; (2) first flow, i.e., the first measured hyperemic blood flow in the calf after ischemia or exercise; (3) peak flow, i.e., the maximum blood flow recorded during hyperemia; (4) time of peak flow, i.e., the time in seconds when the maximum blood flow was recorded; and (5) time course for recovery of basal flow, i.e., the duration of the hyperemia. The significance of mean differences in quantifiable variables among groups was determined by application of the student t test. The r coefficient was used to correlate variables within the
same
group.
Resul ts
.
Table 1 shows the values of basal and hyperemic blood flows and the time for the recovery of basal flow in healthy subjects. First flow and peak flow coincide. There is no significant difference in the peak flow after 5-minute ischemia or exercise with a load of 50 kg. The duration of hyperemia is significantly longer after exercise (P < .001). When the muscular load is 30 kg, the first and peak flows of exercise hyperemia are lower than in reactive hyperemia (P < .001). The time course for recovery of basal flow is similar. Table 2 shows the behavior of reactive and exercise hyperemia with variable work loads until the occurrence of pain in 25 limbs of 16 subjects with PAD. First flow, peak flow and duration of hyperemia are significantly higher after exercise than after ischemia (P < .001). Similar results (Tables 3 and 4) are course
TABLE 1 Mean Values
of Reactive and
Exercise
Hyperemia
in 10 Limbs
from
I S Normal
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
Subjects
42 TABLE 2 Mean Values
of Reactive and Exercise
Hyperemia
in 25 Limbs
from
16 Patients with PAD
obtained when the comparison of the hyperemias is made in relation to the work load. Only the peak flow of exercise hyperemia with a work load of 25-35 kg does not differ from that of reactive hyperemia (Table 3). No correlation between first flow and peak flow can be demonstrated by using the r coefficient on the values found in PAD. There is positive correlation between the time of peak flow and duration of hyperemia (Table 2). The typical course of reactive and exercise hyperemia in normals and in subjects with PAD is shown in Figures 1 and 2. The duration and excess blood flow in the calf increase much more after exercise than after ischemia. Discussion
The results of this study provide further evidence that in healthy subjects the only difference between exercise and reactive hyperemia is in the duration of recovery time for basal flow, when the muscular work load is 50 kg. Therefore, in normal limbs, maximum hyperemic flow can be evoked either by a fiveminute ischemia or by muscular work of 50 kg. The longer duration of exercise hyperemia can be attributed to a greater release and concentration of vasodilating substances in tissue fluids. Our data also demonstrate that reactive and exercise hyperemia differ significantly when arterial obstruction is present, as in arteriosclerosis obliterans of TABLE 3
Comparison
Between Mean Values
of Reactive and Exercise Hyperemia With PA D
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
in 12 Limbs From 11 Patients
43 TABLE 4
Comparison
Between Mean Values
of Reactive and Exercise Hyperemia in 5 Limbs From 4
Patients With PAD
the lower limbs. First flow and peak flow are higher and recovery time more prolonged after exercise. No correlation is demonstrable between the two hyperemic flows. These findings could be interpreted to mean that in PAD the two hyperemias are independent both in mechanism and expression. It is likely that the muscular work, when protracted until pain occurs, as in this study, produces in the calf muscles a metabolic and circulatory adjustment other than that of ischemia. This different behavior of reactive and exercise hyperemia in PAD can be explained without postulating different local metabolites or nervous mechanisms of a special kind. It is well established that the hyperemic reaction is a locally mediated phenomenon.6,15,23 It is possible that a myogenic mechanism, as stressed by Bayliss and Folkow,24,25 is present in both hyperemias, even though the initiating changes are different. 26-28 The distribution of the hyperemia is broadly similar, because in periods of ischemia of five minutes or less the contribution of the skin is quite small.17 Two metabolic hypotheses can be postulated: (1) release in the calf muscles, upon the occurrence of pain, of a substance or substances that do not appear in reactive hyperemia; (2) greater concentration of the same metabolites and possible interaction between them. Many substances can be involved in exercise and reactive hyperemia, but only a few have been identified .6 Their concentration in tissue fluids surrounding resistance vessels produces a change in the vascular tone of small arteries, arterioles, and metarterioles, allowing a blood flow adjustment. The purpose of the hyperemic reaction and the mechanism responsible for its decrease is still not clear. The metabolites can be destroyed locally, washed away, or facilitate their entry into cells to restore normal concentration.18 No close relationship can be demonstrated between hyperemic reaction and blood-debt repayment, as suggested by the classic experiment of Blair et al. 21 At present, there is no positive evidence that the metabolites are different in reactive and exercise hyperemia. It may be that their release is greater and that the magnitude and the time course of their concentration in interstitial fluids are greater after muscular exercise than after ischemia. It follows that the changes in osmolality, pH, and 02 uptake show a similar course.
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
44
FIG. 1.
Typical course of reactive and exercise hyperemia (work load 30 and 50 kg) in normal subjects.
On the other hand, we must consider the different behavior of muscular vessels in reactive and exercise hyperemia. In working hyperemia, dilation occurs not only in the vessels of active units, but also in all the vessels of the whole muscle proportional to the frequency of impulses and number of contracting units. The lasting of the postcontraction hyperemia increases as a linear function of peak blood flow.3° There is also experimental evidence that the
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
45
FIG. 2.
Typical
course
of reactive and exercise
hyperemia
in
patients
with
peripheral
arterial disease.
increase of flow in previously open capillaries is the primary source of reactive hyperemia31 and the opening of new vessels of exercise hyperemia.30 The mechanical effect of muscular contraction on calf blood flow, which is present during exercise and absent during ischemia, should be stressed. Since muscle tissue is enclosed by a tight fascia, contractions will produce an increase in tissue pressure, which in turn will have a double effect on the blood circulation in the calf. Arterial inflow will be temporarily impeded because of a &dquo;nipping&dquo; effect on the arteries, and venous outflow will be enhanced because of a compression on the venous wall.32 It follows that in muscular relaxation the venous pressure is markedly reduced, and this lowering raises the effective arterial perfusion pressure.
Summary Reactive and exercise hyperemia were compared in healthy men and in patients with PAD. In both patients and normals the calf blood flow of reactive
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
46
recorded after a 5-minute ischemia. Exercise hyperemia was measured in normals after variable work loads (30 and 50 kg) and immediately after the occurrence of pain in patients with PAD. In healthy limbs the first and peak flows of exercise and reactive hyperemia are similar. The recovery time for basal flow is prolonged after exercise. However, reactive and exercise hyperemia differ significantly when arterial obstruction due to arteriosclerosis obliterans is present. First flow and peak flow are higher and recovery time more prolonged after exercise. It is also likely that the control mechanisms of the two hyperemic reactions are different. Muscular exercise, when protracted until pain occurs, can produce a metabolic and circulatory adjustment other than that of ischemia. There is experimental evidence to support this hypothesis.
hyperemia
was
Vittorio Bartoli, M.D., F.I.C.A. Via Mannelli, 203 50132 Florence, Italy
References 1.
2.
3. 4.
5.
6. 7.
8.
9.
10.
11.
12.
creases
Barcroft, H.: Circulation in skeletal muscle, in Handbook of Physiology. Section 2: Circulation. Vol. II. Washington, American Physiology Society, 1963, p. 1353. Shepherd, J. T.: Physiology of the Circulation in Human Limbs in Health and Disease. Philadelphia, W. B. Saunders, 1963, p. 127. Chapman, C. B. (ed.): Physiology of Muscular Exercise. Circ. Res., 20: Suppl. 1, 1967. Whelan, R. F.: Control of the Peripheral Circulation in Man. Springfield, Charles C. Thomas, 1967. Strandness, D. E., Jr.: Peripheral Arterial Disease. A Physiologic Approach. London, J. & A. Churchill, 1969. Zelis, R. (ed.): The Peripheral Circulations. New York, Grune & Stratton, 1975. Rodbard, S (ed.): Local Regulation of Blood Flow, Circ. Res., 28: Suppl. 1, 1971. Tominaga, S.: Local regulation of blood flow in the skeletal muscle: Probable participation of adenosine. Scand. J. Clin. Lab. Invest., 29: 129, 1972. Hilton, S. M.: Evidence for inorganic phosphate as the initiator of post-contraction hyperaemia in skeletal muscle. Scand. J. Clin. Lab. Invest., 29: 135, 1972. Mellander S.: Tissue osmolality as a mediator of exercise hyperemia. Scand. J. Clin. Lab. Invest., 29: 139, 1972. Eklund, B.: Influence of work duration on the regulation of muscle blood flow. Acta Physiol. Scand., Suppl. 411, 1974. Järhult, J., Hillman, J., Mellander, S.: Circulatory effects evoked by "physiological" in-
of arterial
osmolality.
Acta
Physiol.
Scand., 93: 129, 1975. 13. Haddy, F. J., Scott, J. B.; Metabolic factors in peripheral circulatory regulation. Fed. Proc., 34: 2006, 1975. 14. Eichna, L. W., Wilkins, R. W.: Reactive hy-
peremia : Factors influencing the blood flow during the vasodilatation following ischaemia. Bull. Johns Hopkins Hosp., 68: 450, 1941. 15.
Dornhorst, A. C., Whelan, R. F.: The blood
flow in muscle following exercise and circulatory arrest: The influence of reduction in effective local blood pressure, of arterial hypoxia and of adrenaline. Clin. Sci., 12: 33, 1953. 16. Hilton, S. M.: Experiments on the post-contraction hyperaemia of skeletal muscle. J. Physiol. (Lond.), 120: 230, 1953. 17. Dornhorst, A. C.: Hyperaemia induced by exercise and ischaemia. Br. Med. Bull., 19:
137, 1963. W. H.: Nature and mechanism of the restoration of normal blood flow after exercise and ischemia, in Circulation in Skeletal Muscle. Edited by O. Hudlickà. Oxford, Pergamon Press, 1968, p. 205. 19. Allwood, M. J.: Redistribution of blood flow in limbs with obstruction of a main artery. Clin. Sci., 22: 279, 1962. 20. Strandell, T., Wahren, J.: Circulation in the calf at rest, after arterial occlusion and after exercise in normal subjects and in patients with intermittent claudication. Acta Med. Scand., 173: 99, 1963. 21. Hillestad, L. K.: The peripheral blood flow in 18.
Hyman, C., Wong,
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
47 intermittent claudication. VI. Plethysmographic studies. The blood flow response to exer22.
23.
24.
25.
26.
27.
cise with arrested and free circulation. Acta Med. Scand., 174: 671, 1963. Pirri, F., Zanini, A., Dorigo, B., et al.: A new electronic foot ergometer for direct reading of muscle work load. Angiology, 28: 770, 1977. Bevegard, B. S., Shepherd, J. T.: Regulation of the circulation during exercise in man. Physiol. Rev., 47: 178, 1967. Bayliss, W. M.: On the local reactions of the arterial wall to changes of internal pressure. J. Physiol. (Lond.), 28: 220, 1902. Folkow, B.: Description of the myogenic hypothesis. Circ. Res., 14-15: Suppl. 1, 279, 1964. Arai, M., Endoh, H.: Blood flow through human skeletal muscle during and after contraction. Tohoku J. Exp. Med., 114: 379, 1974. Owen, T. L., Ehrhart, I. C., Scott, J. B., et al.: A comparison of recovery times from exercise
28.
29.
30.
31.
32.
and ischemic dilations at constant pressure and flow. Proc. Soc. Exp. Biol. Med., 149: 1040, 1975. Haddy, F. J., Scott, J. B.: Metabolic factors in peripheral circulatory regulation. Fed. Proc., 34: 2006, 1975. Blair, D. A., Glover, W. E., Roddie, I. C.: The abolition of reactive and post-exercise hyperaemia in the forearm by temporary restriction of arterial inflow. J. Physiol. (Lond.), 148: 648, 1959. Khayutin, V. M.: Determinants of working hyperaemia in skeletal muscle, in Circulation in Skeletal Muscle. Edited by O. Hudlickà. Oxford, Pergamon Press, 1968, p. 145. Burton, K. S., Johnson, P. S.: Reactive hyperemia in individual capillaries of skeletal muscle. Am. J. Physiol., 223: 517, 1972. Folkow, B., Gaskell, P., Waaler, B. A.: Blood flow through limb muscles during heavy rhythmic exercise. Acta Physiol. Scand., 80: 61, 1970.
Downloaded from ang.sagepub.com at University of Otago Library on March 12, 2015
