Counterpoint: The muscle pump is not an important determinant of muscle blood flow during exercise.

It is well known that muscle contractions evoke an immediate increase in blood flow to active skeletal muscle (1, 2, 4, 5, 8, 9, 11– 15). In fact, studies employing both human and animal models have shown that skeletal muscle blood flow is significantly elevated within 1 s after the release of a brief contraction (2, 11, 13, 14). A potential mechanistic explanation invokes the concept of the muscle pump, which is hypothesized to elevate skeletal muscle blood flow by mechanical rather than metabolic factors (6). As the muscle contracts, the veins within the muscle are compressed and the venous contents are expelled. On relaxation, it is thought that the muscle fibers (which are tethered to the walls of the veins) open the lumen of the compliant vessels and create low pressure (6, 7). The reduction in venous pressure increases the pressure gradient across the muscle vascular bed and enhances muscle perfusion. Ideally, to support this hypothesis one need only measure the fluctuations in venous pressure within the muscle during contractions. Unfortunately, it has been technically impossible to measure pressure in the venules of skeletal muscle. This technical limitation has created a situation in which the muscle pump theory has persisted despite the lack of direct confirmation. On the basis of the available data, we contend that the muscle pump is not an important determinant of muscle blood flow during exercise. Our position is based on three lines of evidence. First, the magnitude of contraction-elicited changes in blood flow is far greater than can be accounted for by putative changes in intravascular pressure. Second, the time course of changes in blood flow does not correlate with that predicted from the muscle pump. Third, in the absence of vasodilation, muscle contractions do not evoke an increase in muscle blood flow. By definition, the muscle pump can only influence blood flow for as long as venous pressure is reduced. Once arterial inflow replaces the volume of blood expelled during contraction, venous pressure is restored and there can be no further effect of the muscle pump on blood flow. Therefore, the proportion of skeletal muscle hyperemia attributable to the muscle pump should be directly related to the volume of blood needed to replace that expelled from the veins. Evaluation of this idea is facilitated under experimental conditions where the refilling of the veins is not interrupted by a subsequent contraction, i.e., a single brief contraction. In anesthetized dogs positioned in an upright position to maintain a normal hydrostatic gradient, we obtained continuous measurements of arterial and venous blood flow before, during, and after maximal tetanic contractions of 1-s duration evoked by electrical stimulation of the sciatic nerve (15). The volume of blood expelled from the veins during muscle contraction and the volume of blood flowing into the arterial circulation were calculated by integrating the pulsatile blood flow tracings. In the horizontal upright position, muscle contraction ejected a volume of 1.6 _ 0.2 ml from the venous circulation. The cumulative arterial blood volume amounted to 32.9 _ 4.4 ml. Because the venous circulation should have been refilled by the first 1.6 ml of blood, the additional 30_ ml of blood must be explained by some other mechanism. Thus under these conditions, the muscle pump can be responsible for only a small percentage of the total arterial inflow after contraction. If the muscle pump is the primary determinant of the initial blood flow response to contraction, then one would expect the peak blood flow to be observed in the first few cardiac cycles after a single contraction. That time course is not what is observed in the human forearm or canine hindlimb. Studies using continuous Doppler ultrasound measurements in humans show an immediate contraction-induced elevation in arterial blood flow with a peak occurring 4– 5 s after release of contraction (1, 9, 13, 14). With the use of the same canine model described above, arterial blood flow was elevated within the first second after contraction and then increased progressively until reaching a peak at 4– 7 s (11, 15). Furthermore, at the prevailing blood flows in the dog, it can be calculated that the venous volume expelled would have been refilled in _1 s, eliminating the basis for any muscle pump effect after this time. Thus careful analysis of the time course of the blood flow response to a single contraction reveals a progressive increase in blood flow and temporal dissociation of the peak blood flow effect from the presumed contraction-related changes in intravascular pressure. This time course is incompatible with the postulate of the muscle pump playing the primary role in the observed hyperemia. One of the challenges for investigators interested in this topic is that the muscle pump and vasodilator mechanisms may be activated simultaneously (13, 16). It would be desirable to study the muscle pump in isolation without any dilation of the skeletal muscle vasculature. A novel experimental approach to accomplish this objective in vivo is to infuse K_ intra-arterially to raise the external potassium concentration, which clamps the membrane potential in a depolarized state, rendering the vascular smooth muscle unable to relax. In anesthetized dogs, the increase in hindlimb blood flow after tetanic contraction was prevented by intra-arterial infusion of K_ (4). That is to say, in the absence of vasodilation, there was virtually no change in blood flow. The K_ infusion protocol did not alter the force produced by contraction, indicating that this experimental manipulation should have had no discernible effect on muscle pump function. Another method of impairing the dilator ability of the skeletal muscle vasculature is to infuse a potent vasodilator to elicit maximal vasodilation before initiating contractions. When this approach was employed in anesthetized animals, muscle contractions did not further increase blood flow (3, 10), except in the case of spontaneous contractions of the diaphragm (10). One drawback of in situ exercise models is that electrical stimulation simultaneously activates all the fibers within the muscle (synchronous contractions). The fact that spontaneous diaphragmatic contractions increased diaphragm blood flow (10) prompted the suggestion that the muscle pump may be more effective in dynamic exercise when the muscles are contracting asynchronously (6). Experiments in our laboratory (5) used a similar approach of minimizing changes in local vascular tone by infusing high doses of adenosine before the commencement of treadmill exercise in conscious dogs. Under these conditions, voluntary contractions failed to increase blood flow to the exercising muscles. A straightforward interpretation of our data is that the magnitude of any change in venous pressure elicited by the muscle pump was inadequate to elevate blood flow at the onset of exercise. Taken as a whole, data isolating the influence of the muscle pump (3– 5, 10) do not support the ability of the muscle pump to increase blood flow when the muscle vascular bed is unable to dilate. In summary, examination of the blood flow response to a single contraction reveals that the muscle pump cannot adequately account for the magnitude of the hyperemia nor the time course of the response. Furthermore, there is no increase in muscle blood flow to electrically stimulated or spontaneous contractions when vasodilation is prevented. That the muscle pump aids venous return to the heart cannot be refuted, but the preponderance of the evidence suggests that it is not an important determinant of muscle blood flow during exercise.