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HIGHLIGHTED TOPICS
Skeletal and Cardiac Muscle Blood Flow
1Department of Kinesiology, Kansas State University, Manhattan, Kansas; 2Department of Exercise Science and Physiology, Hiroshima Prefectural Women's University, Hiroshima, Japan; 3Department of Kinesiology, The University of Toledo, Toledo, Ohio; and 4Applied Physiology Laboratory, Kobe Design University, Kobe, Japan
Submitted 26 February 2004 ; accepted in final form 15 November 2004
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ABSTRACT |
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Doppler sonography; exercise hyperemia; recovery hyperemia; vascular conductance; muscle pump
In the present study we sought to clarify the interaction of muscle contraction and blood flow by examining the cardiovascular responses in naturally recruited muscles during voluntary upright knee extension exercise in the dependent limbs of humans. This was accomplished by comparing net blood flow during steady-state exercise with the blood flow observed during the first few cardiac cycles in recovery (after sufficient time for prior effects of muscle contraction, i.e., venous refilling and loss of pressure gradient, to be accounted for) across a series of dynamic work rates that ranged from light to heavy. We assumed that these first few cardiac cycles in recovery would reflect the level of vasodilation and vascular conductance during exercise but without the influence of muscle contractions (9, 12). Assuming also that mean arterial pressure (MAP) remained constant across the exercise-early recovery transition, we hypothesized that 1) if blood flow early in recovery was less than the mean flow during exercise, this would imply a positive net influence of the mechanical effects of muscle contraction-relaxation cycle to facilitate mean exercise blood flow (MBFM) above that achieved by vascular conductance and arterial pressure alone; 2) if the early recovery flow was greater than the MBFM, this would suggest that the net effect of the muscle contraction-relaxation cycle was impedance to flow as seen by Hamann et al. (12) and Dobson and Gladden (9); or finally 3) if early recovery flow was no different that the mean exercise level, this would suggest no net effect of the muscle contraction-relaxation cycle on exercise blood flow under these conditions. In addition, to gain further insight into the consequences of the muscle contraction-relaxation cycle on blood flow, we differentiated blood flow into that associated with muscle contraction (MBFC, usually retrograde) and net flow during the subsequent relaxation (MBFNR). To ascertain whether the MBFNR represented enhanced flow, we compared these values with the blood flow observed during the first few cardiac cycles in recovery (MBFR).
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METHODS |
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Experimental design.
For this experiment, subjects performed discontinuous, incremental one-leg knee extension exercise on a specially built leg ergometer (13). In contrast to our previous work (13), exercise was performed with the subject in the upright seated position, with the thigh parallel to and the lower leg perpendicular to the ground. A strap was then placed around the ankle of the subject and attached to a pneumatic cylinder by means of a cable-pulley system. Work was accomplished by compressing the air in the cylinder as the lower leg was extended. On relaxation, expansion of the gas in the cylinder brought the leg back to the starting position; i.e., knee flexion was passive during the downstroke. This mode of contraction-relaxation cycle is similar to most Krogh-ergometer-based knee extension exercise but is contrary to that used by Shoemaker et al. (32), who utilized both concentric and eccentric contractions, followed by relaxation, as their contraction cycle (which could have limited the effect of the muscle pump in their study). For comparison of blood flow responses to our previous work (13), the distance traveled by the lower limb during knee extension was limited to a fixed linear displacement (d) of the piston of the pneumatic cylinder of 10.9 cm, which represented a range of motion about the knee of 
20°. The amount of work performed (per stroke) was calculated as [PINT + (PF + PINT)/2]·d, where PINT is the initial pressure in the cylinder and PF is the final pressure at the end of the work stroke. This in turn was divided by the duration of the contraction cycle (0.16 s) to yield power (W). Work rate was varied by adjusting the pressure in the cylinder. Actual work rates were 0.07, 1.39, 2.72, 4.05, 5.11, 7.49, and 9.80 W. These represented exercise intensities ranging from 4–5% of maximum voluntary contraction at the lowest intensity to 30–40% at the highest intensity (see Measurements below), or up to 60–75% of the peak work rates as previously determined for this mode of exercise (13). The contraction frequency was set at 40 kicks per minute. A metronome was used to assist the subjects in maintaining the appropriate kicking frequency. Ventilation was not measured, so entrainment of breathing, with its potential effect on venous return, could not be assessed. However, from pilot work, this mode of exercise engenders such a small rise in metabolic rate (<700 ml/min) as to not appreciably affect the breathing rate. Each increment protocol consisted of 1 min rest, 3 min of exercise, and 1 min of recovery. Total time between stages was typically 10–15 min. Before the study, each subject was familiarized with the testing procedures and the exercise protocol by performing at least three to four practice sessions.
Measurements. Instantaneous blood velocity in the right femoral artery was continuously determined by using a Doppler ultrasound velocimetry system (model 500-V, Multigon Industries) operating in pulsed mode. The pulsed-wave Doppler transducer, with an operating frequency of 4 MHz and a fixed insonation angle of 45°, was placed flat on the skin 2–3 cm below the inguinal ligament, above and parallel to the common femoral artery. This position was selected to minimize turbulent flow arising from the bifurcation of the common femoral artery into the superficial and profundus branches. The gate was set at full width to ensure complete femoral artery insonation. The frequency spectrum of Doppler audio signals was converted to an instantaneous mean blood velocity by using a quadrature audio demodulator that was calibrated according to the specifications of the manufacturer (Hokanson). Blood pressure was continuously monitored noninvasively at the radial artery (model 7000, Colin, San Antonio, TX). ECG was obtained using a modified lead I. Software developed in our laboratory (13) was used to calculate femoral artery blood velocity averaged over one cardiac cycle between the R-R interval. The instantaneous cardiovascular (blood velocity, blood pressure, and ECG) and ergometer data (displacement, pressure) were digitized and stored for offline analysis.
To test the reproducibility of the protocol and data analysis, a separate study was performed on one subject. On 4 consecutive days with approximately the same conditions each day, the subject performed a protocol similar to the primary study but utilizing only two work rates (2.3 and 7.0 W). All measurements and data analysis were the same as for the primary study.
On a separate day, the femoral artery cross-sectional area (CSA) was determined by using a duplex Doppler computed sonography system (Acuson model 128XP) in two-dimension echo mode. The vessel diameter was determined at rest in the upright position from a cross-sectional view of the artery at the level used to measure blood velocity. From the images stored on VHS tape, 10–15 measurements were randomly made where the proximal and distal vessel walls were most accurately visualized. The mean of these measurements was then used to calculate an average CSA, which in turn was used to convert velocity to flow.
To determine whether the diameters of the resting femoral artery were representative of exercise values, and to validate the assumption of constant femoral artery diameters in the exercise-to-recovery transition, five different subjects performed a similar exercise protocol in which the femoral artery CSA was recorded continuously during the protocol by duplex Doppler computed sonography (Acuson model 128XP). Work rates were set at 30 and 60% of the maximum work rate achieved during a previous incremental exercise test. Ten measurements were taken for each subject, and work rate was measured during both the systolic and diastolic phases at rest, exercise, and for the first four to five cardiac cycles in recovery (14).
To compare the generated muscle force with our previous work (13) and with other modes of exercise, maximum voluntary contraction (MVC) for each subject was determined in the same position that the knee extension was performed (upright with knee bent at 90°). Each subject performed three maximum isometric efforts for 5 s each, with 2-min rest in between, against a fixed cable connected to a force transducer.
Data analysis. From the cardiac cycle-averaged blood flow responses, three characteristics, two during exercise and one during early recovery, were determined as follows. MBFM was defined as the average blood flow over the last 30 s of exercise. The peak oscillations in blood flow during exercise (MBFPO) were calculated as the mean of the 10 highest values of blood flow during exercise. The early recovery muscle blood flow (MBFR) was determined from the average of the first four cardiac cycles in recovery, after allowance for the equivalent time of a complete contraction-relaxation cycle for the last contraction of the exercise bout (see Fig. 1). This was done to allow for any residual effect of the last muscle contraction and muscle pump effect to dissipate.
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For each of the time points of observation of the blood flow response (the means, peak oscillations, early recovery, net relaxation, and contraction), corresponding values of MAP were also determined. Because an ohmic conductance does not exist across a pump (18), vascular conductance was only calculated for early recovery, as MBF/MAP.
Statistics. Group summary data are presented as means ± SD. For each of the cardiac cycle-derived primary variables (blood flow and MAP), data were initially analyzed by using a two-way ANOVA with two repeated measures to examine main effects of power output (stages 1–7) and data point (mean, peak oscillation, and early recovery) by use of NCSS 2000. Similarly, for the contraction-cycle-based blood flows, data were initially analyzed by a two-way ANOVA with two repeated measures to examine main effects of power output (stages 1–7) and data point (net MBF during relaxation and cardiac-cycle-derived early recovery MBF) A two-way ANOVA with two repeated measures (power output, time) was used to test the femoral artery diameters for rest, exercise, and early recovery. Post hoc testing of significant results was performed with a Fisher's least significant difference multiple-comparison test. In all cases, significance was declared when P < 0.05.
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RESULTS |
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10%, and with the exception of MBFR they were lower at the higher work rate.
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DISCUSSION |
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60–75% peak work rate, on the basis of our laboratory's previous work (13)] during upright knee extension exercise. The primary finding is that at the lightest work rate rhythmic muscle contraction enhanced MBFM, compared with blood flow early in recovery. Above this work rate, there was no systematic enhancement of mean MBF during steady-state exercise. In fact, at the higher work rates, there was evidence that the net effect of muscle contraction-relaxation was impedance to flow. During dynamic exercise, MBF is determined by skeletal muscle vascular conductance, the perfusion pressure gradient, and the efficacy of the muscle pump (6, 18, 23). With regard to the last, there is ample evidence from a variety of studies that muscle contraction transiently increases venous outflow from the muscle and/or limb (9, 29). The fundamental controversy lies in whether the overall effect of muscle contraction (pump) is to enhance the net (average) MBF, decrease the net flow, or have no discernable effect. There is evidence that the muscle pump can actively assist muscle perfusion (26, 29) and accounts for much of the immediate rise in vascular conductance at the onset of exercise, before metabolic vasodilation (19, 27, 28). Tschakovsky et al. (35) demonstrated with rhythmic cuff inflation and deflation that MBF at rest can be enhanced by a mechanical muscle pump effect. Furthermore, Shiotani et al. (31) found that, in humans, cycling in the upright position under near-unloaded conditions (5 W) was associated with twice the femoral arterial blood flow, presumably via the venous muscle pump, compared with cycling at the same light work rate in the supine position. However, this difference disappeared as the work rate was ramped up to 45 W over 60 s (31). Our results are similar to those of Shiotani et al. in that MBFM was significantly greater than early recovery for the lightest work rate, but this difference disappeared as the work rates became greater (with the isolated exception of stage 5).
In contrast, a recent study by Hamann et al. (12) found no evidence for a muscle pump enhancement of peak MBF. In their preparation, conscious dogs standing on a treadmill were maximally adenosine vasodilated. The onset of locomotion failed to further elevate blood flow. Dobson and Gladden (9) also found no evidence of the muscle pump enhancing peak MBF during electrical stimulation of isolated dog gastrocnemius muscle. However, the unphysiological recruitment patterns of electrically activated muscle in that study may not have engaged the muscle pump effectively (16). Our present data, gathered under conditions of natural muscle and vascular recruitment during moderate steady-state exercise, extend these observations. As such, our results suggest that any net enhancement to MBF by the muscle pump occurred only at very light work rates but that for moderate and higher work rates there was generally no net effect of the muscle pump to augment net MBF during steady-state submaximal, upright knee extension exercise.
To assess any potential effect of the muscle pump to augment net exercise blood flow, we compared mean MBF during steady-state exercise to early recovery blood flow, after allowing time for any effects from the exercising period (i.e., venous refilling and loss of pressure gradient) to elapse. Because blood flow values during the first four cardiac cycles during early recovery were not significantly different from each other, this suggested that changes in vascular tone (conductance) had not yet occurred. Generally, MBFM was similar to recovery blood flow (except for stages 1 and 5). There was no significant change in MAP from exercise to early recovery for stages 1–4, suggesting that for stages 2–4, the muscle pump did not augment blood flow above that achievable by blood pressure and vascular conductance alone (Fig. 8). From stages 5 to 7, MAP was progressively higher during exercise than during recovery. Because MBFNR again was generally similar to MBFR, this suggested that the net effect of the muscle contraction-relaxation cycle was progressive impedance to flow, which necessitated a higher MAP to achieve the mean exercise flow under these conditions (Fig. 8).
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A critical assumption in the present study was that vascular conductance and blood flow (MBFR) during the first few cardiac cycles in recovery from dynamic exercise reflected the state of the peripheral circulation during the exercise period but in the absence of any mechanical influence of muscle contraction itself (analogous to a submaximally vasodilated animal model) (9, 12). To our knowledge, little work has been reported to date regarding the timing of changes in vascular conductance immediately on cessation of exercise. Because vascular conductance cannot be measured across a pump such as rhythmically contracting muscle (18), we could not directly determine vascular conductance during exercise to validate this assumption. However, evidence regarding the onset of vasodilation after application of a dilatory stimulus indirectly supports our assumption. For example, Wunsch et al. (39) found that potassium chloride, adenosine, acetylcholine, and sodium nitroprusside applied directly to isolated rat arterioles each exhibited a delay of 5 s before vasodilation occurred. Similarly Sheriff and Zidon (30) found an 5 s delay in the onset of vasodilation after grade changes during treadmill running in rats. Furthermore, once vasodilation had been initiated, the overall response took several seconds to reach a peak (30, 34, 39) and, relevant to our assumption, several more seconds to decay after even a single contraction (35). In contrast, smooth muscle hyperpolarization (11) and/or contraction-induced mechanical distortion of the arterial resistance vessels (34) have recently been suggested as putative mechanisms for rapid (within 2 s) vasodilation after exercise onset. It remains uncertain whether removal of either of these two stimuli or mechanisms on cessation of exercise is rapid enough to invalidate our assumption. Thus, on the basis of the present data, our assumption that early recovery blood flow reflects the state of the peripheral circulation during the exercise period, without mechanical interference from muscle contraction, appears to be valid. A similar conclusion was reached by Shiotani et al. (31) for femoral artery blood flow in the immediate recovery from upright cycle exercise. [N.B. If this assumption is wrong, i.e., if the first few cardiac cycles in recovery do reflect a reduced vascular conductance relative to that of exercise, this would imply that the method used here (the difference between exercise relaxation and early recovery blood flow) would overestimate the contribution of the muscle pump to the exercise blood flow.]
Contraction-induced oscillations in MBF have been recognized for over 50 years (3). In each investigation in which MBF has been reported on a contraction-by-contraction basis (2, 4, 20, 22, 23, 32, 33, 37), impedance of blood flow during contractions, due to increased intramuscular pressure (25), has been noted. In the present study, we were able to observe significant flow impedance, and even retrograde flow in the femoral artery, at surprisingly low muscle tensions (4–5% MVC, Fig. 6), similar to that reported by Robergs et al. (24) for forearm exercise (6% MVC) but half of the lowest work intensity (10% MVC) for knee extension exercise observed by Walloe and Wesche (37). Our laboratory has previously observed that retrograde blood flow during incremental continuous exercise in the supine position reached a constant, maximum value of 3–4 ml/contraction at very light muscle forces and power outputs (13), similar to that observed in the present study (4 ml/contraction). Kagaya and Ogita (15) also reported no significant change in blood flow during the contraction phase of rhythmic handgrip exercise over a range of muscle forces (10 and 30% MVC) similar to that employed here. This pattern of response (relatively constant minimum blood flow during contraction at higher power outputs) is similar to those reported for brachial artery blood flow during wrist flexion-extension exercise (24).
It is interesting to note that the mode of exercise performed here [knee extension exercise over a limited (20°) range of motion] might be considered less likely than normal locomotion to demonstrate an effect of the muscle pump (16). For comparison, running typically is associated with a range of motion of 37° around the knee (from 165° at contact to 128° at maximum flexion) (7, 8), whereas cycling may elicit a range of knee movement of 74°, depending on relative seat height (21). Also, the more common Krogh-style knee extension ergometer is associated with a range of motion of up to 80° (1). Thus, although not isometric, our mode of muscle contraction represents a smaller range of motion than would be encountered in other forms of exercise, both stationary and locomotory. Even so, we were able to detect wide oscillations about the mean blood flow that represented the impedance and subsequent enhancement to flow (muscle pump) caused by our mode of muscle contractions.
Because of conflicting data in the literature regarding vessel diameter changes during dynamic exercise (5, 15, 20, 22, 36), we assessed the diameter of the femoral artery during the rest-to-exercise and the exercise-to-recovery transitions in a different group of subjects. We found no change in femoral artery diameter from rest to exercise to early recovery for two work rates comparable to those performed in the present study, validating our use of diameters determined at rest as representative of exercise values, similar to the conclusions of Radegran (22), Shiotani et al. (31), and DeLorey et al. (5).
In summary, we have quantified the net contribution of the muscle pump during steady-state upright knee extension exercise by comparing mean blood flow during exercise to early recovery blood flow across a wide range of submaximal work rates in humans. Furthermore, by comparing blood flow during the relaxation phase between contractions to the early recovery flow, assuming vascular conductance remained unchanged from the exercise level, we were able to quantify the potential enhancement effect of the muscle contraction-relaxation cycle to MBF. For the lightest work rate, MBFM was greater than during recovery, suggesting a muscle pump-induced enhancement to flow. For the next intermediate work rates (stages 2–4), the net effect of the muscle pump was neutral; i.e., it neither enhanced nor impeded net blood flow. At the heavier work rates the increased impedance to flow with increased contraction force was not fully compensated for by any enhanced flow during relaxation. This required an increase in MAP during the exercising phase so as to maintain mean MBF at a level equivalent to that set by vasodilation.
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GRANTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES |
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, Average blood flow during corresponding cardiac cycle. Dotted vertical line shows equivalent time for contraction-relaxation cycle for last kick (i.e., time of onset of the next contraction, if existed). PO, peak exercise oscillations. R, first cardiac cycle in recovery fully after the time for the last relaxation period (i.e., after the dotted line). R2, R3, and R4 represent the next 3 consecutive cardiac cycles in recovery. Note oscillatory behavior of blood velocity-flow curves due to intermittent effect of muscle contraction to impede flow, followed by augmented flow during the relaxation phase, relative to early recovery blood flow. Also note secondary, intermittent smaller peak in blood pressure associated with muscle contraction and retrograde flow in the femoral artery.
), and 7th (
) stages are shown.
); peak exercise oscillation (MBFPO, 
); early recovery hyperemia (MBFR, 
) and MBFR (
