The following letters are in response to the Point:Counterpoint series “The muscle metaboreflex does/does not restore blood flow to contracting muscles” that appears in this issue (vol. 100: 357–361, 2006; doi: 10.1152/japplphysiol/01222.2005; http://jap.physiol.org/content/vol100/issue1/2006).
To the Editor: Does the muscle metaboreflex restore blood to contracting muscle? The question is difficult and the answer remains controversial because investigators have yet to devise an ideal preparation for its study. The present Point:Counterpoint highlights this problem but the muscles of respiration may provide some insight. First, Dr. Joyner (3) points out that respiratory loading during heavy cycle exercise causes a reduction in leg blood flow (1). Indeed, for a ±50% change in the work of breathing, leg blood flow changed 2 l/min or 11% of control, which was accompanied by changes in norepinephrine spillover. Similar to limb muscle, increases in sympathetic activity appear to be triggered by metaboreceptors in the diaphragm (2). Second, it has been shown that during treadmill exercise, lactic acid injected into the phrenic or deep circumflex iliac arteries of dogs elicits pressor responses and reduces hindlimb blood flow and vascular conductance (4). It appears that limb muscles in both exercising humans and dogs are susceptible to sympathetically mediated vasoconstriction from a metaboreflex originating in respiratory muscle. Of course, the increased sympathetic outflow is likely directed to the diaphragm as well as to limb muscle and it is not known if there is a corresponding increased blood flow to the respiratory muscles. John Hunter (1794; Ref. 5) stated that “blood goes where it is needed.” This statement has considerable appeal; if a respiratory metaboreflex-induced reduction in human or dog limb blood flow does not increase blood flow to the contracting respiratory muscles, where else is it needed?
- Copyright © 2006 the American Physiological Society
To the Editor: The Point:Counterpoint by Dr. O'Leary and Dr. Joyner (3) is concerned with whether the muscle metaboreflex restores blood flow to contracting muscles; that is, whether the metaboreflex is a flow-sensitive, flow-raising reflex or a flow-sensitive, pressure-raising reflex that leads, ultimately, to vasoconstriction also in contracting muscles, thus preventing restoration of blood flow (3).
Data by Dr. O'Leary in dogs are straightforward in indicating that the muscle metaboreflex partially restores blood flow to underperfused contracting muscles during submaximal exercise, primarily through an increased overall cardiac performance (3).
Dr. Joyner, who quotes studies from his and other laboratories, is concerned that no similar evidence exists in humans (3). However, most of these studies focused on exercise of small muscle masses. The regulatory mechanisms attending cardiovascular responses to exercise may differ according to the type of exercise and size of active muscle mass (1).
Indeed, some evidence that the muscle metaboreflex would be capable of partially restoring blood flow to underperfused muscles exists also in humans (2, 4, 5). We reported (2) a greater HR response to mild-intensity, electrically induced dynamic leg extension performed under ischemic conditions in comparison to intensity-matched, electrically induced exercise under free-flow condition and voluntary exercise. This was accompanied by a greater pressor response. If stroke volume at this low exercise intensity remained constant, as outlined by Dr. O'Leary (3), then the reflex tachycardia increased CO, which would account for the greater pressor response to partially restore blood flow to underperfused muscles.
Clearly, if maximal vascular conductance outweighs the maximal pumping capacity of the heart, then vasoconstriction in exercising muscles may ensue to maintain blood pressure.
To the Editor: Although we have not performed the all-inclusive investigation in humans of measuring leg blood flow, we have indeed performed dynamic leg exercise with lower body positive pressure (LBPP) of 0, 15, 30, and 45 Torr (5) while measuring cardiac output (Qc). When estimations were made for the 11-mmHg rise in blood pressure at rest caused by LBPP, a 5-mmHg rise in MAP was due to the change in Qc (+45%), whereas the remainder was increased through changes in TPR (+55%). At 60% Vo2peak, blood pressure increases involved a 30% change in Qc coupled with a 70% change in TPR, whereas at 85% Vo2peak the Qc changed 10% with a 90% change in TPR. Thus there appeared to be an increasing contribution from changes in TPR at higher exercise intensities. These findings confirm the data of Saltin (3) and Secher et al. (4) in which the humans' maximal vascular conductance far exceeds maximal Qc and therefore requires active vasoconstriction to maintain arterial blood pressure during whole body exercise. We suggest that these findings identify a species difference between the human and the dog and provide a compromise in the interpretation of O'Leary's point(s) and Joyner's counterpoint(s) (2), especially when the recent work of O'Leary's group (1) identifies that in the congestive heart failure exercising dog model (i.e., when the Qc is limited), activation of the muscle metabaroreflex uses peripheral vasoconstriction as the primary pressure-raising mechanism.
To the Editor: When considering the importance of the metaboreflex and whether or not cardiac output (CO) or total peripheral resistance (TPR) increases, the bottom line is whether this reflex causes enhancement of the blood flow to the ischemic muscle. This is simply whether the relative increase in arterial pressure exceeds the change in resistance of the ischemic muscle. This requires the direct measurement of blood flow of this ischemic muscle.
Both O'Leary and Joyner (1) suggest that if CO does not increase, then TPR will increase. Does this suggest that the CNS is aware that CO did not change and switches sympathetic output to increase TPR? I would propose that when CO changes are limited, then muscle ischemia becomes more enhanced, resulting in a larger reflex activation that recruits more sympathetic activity and causes more TPR changes.
Other vascular bed responses can complicate the story, particularly the role of renal and cutaneous vascular beds. For example, in humans, if body temperature rises significantly during exercise, sweat gland activation and bradykinin release may secondarily cause a large decreased cutaneous vascular resistance that may not be readily altered by vasoconstrictor sympathetic activity induced by the metaboreflex.
In addition, and perhaps a topic for another point:counterpoint discussion, the metaboreflex may account for much of the exercise-induced shift of the arterial baroreflex response curves at higher arterial pressures. This need to integrate other functional systems is what makes physiology so fun!