A large slice of cardiac output or humble pie for the respiratory muscles?

First estimates of human skeletal muscle blood flow during exercise, utilizing the 133Xe clearance method in the sixties, left humans looking rather inadequate compared to other mammals, but suggested cardiac output was well matched with potential skeletal muscle demand. In this light, it was somewhat of a surprise when, in 1977, the addition of intense arm cranking, which presumably increased total demand for skeletal muscle blood flow, reduced blood flow in the exercising legs (Secher & Volianitis, 2006). Although these data questioned the premise that skeletal muscle perfusion could not outstrip the pumping capacity of the heart, several subsequent studies failed to replicate this finding, probably due to differences in experimental design (e.g. Richardson et al. 1995). However, more recent studies have confirmed the concept that the cardiac output ‘pie’ needs to be carefully ‘sliced’ to adequately perfuse skeletal muscle during whole body exercise compared to when smaller muscle groups are recruited in isolation. This is particularly noticeable during exercise, which demands the use of both the arms and legs, for example during cross-country skiing. There does not seem to be a hierarchy amongst locomotor muscles which dictates that differing limb muscles receive a greater or lesser slice of the total available cardiac output, Specifically, the addition of arm exercise to leg exercise attenuates blood flow in the legs while the addition of leg exercise to arm exercise can reduce blood flow in the arms (Secher & Volianitis, 2006). The explanation for this need to attenuate skeletal muscle blood flow came with a series of human skeletal muscle blood flow studies, performed with both thermodilution and Doppler ultrasound techniques, during isolated single leg knee-extensor exercise. To date the highest reported skeletal muscle blood flow is 3.75 l kg−1 min−1 in highly trained cyclists performing this exercise modality (Richardson et al. 1995). In parallel with these developments, it is recognized that xenon diffuses into the intramuscular fat stores, making its clearance too slow to accurately reflect blood flow. Thus, if skeletal muscle blood flow can indeed range from 2 to 4 l kg−1 min−1 across untrained to trained humans, an equal simultaneous demand from all skeletal muscles would require a cardiac output severalfold greater than the highest recorded to satisfy potential need. Hence, the term ‘a sleeping giant’ has been coined to describe the skeletal muscle's potential demand for blood flow. The recognition of a finite cardiac output and potentially much greater skeletal muscle demand for perfusion raises the question of which mechanisms are employed to protect blood pressure in this scenario. The most obvious is sympathetically mediated vasoconstriction, documented by superimposing forearm exercise on leg exercise, which yielded increased sympathetic activation and attenuated leg blood flow (Saito et al. 1992), and the increase in noradrenaline spillover across the exercising muscle bed when cardiac output is limited by beta blockade (Secher & Volianitis, 2006). Another likely strategy is to increase cardiac output to maintain the required blood pressure. However, if the blood pressure the arterial baroreceptors are set to control beat to beat is not established by the increase in cardiac output, total peripheral resistance needs to be elevated with vasoconstriction also in working skeletal muscles. So, amid this ‘competition’ for a slice of cardiac output the question arises, does the ‘importance’ of some skeletal muscles (e.g. muscles of respiration) protect them from a marked increase in sympathetic activity? As already mentioned there is little evidence of hierarchy between limb muscles, but is there a mechanism that facilitates breathing over movement when cardiac output becomes limiting? Harms et al. (1997) provided evidence of this notion when they documented that increasing or decreasing the work of breathing had the reciprocal effect on blood flow in the exercising legs, suggesting that the respiratory muscles demonstrate some sort of dominance over the locomotor muscles, perhaps by greater sympatholysis in the face of an increasing drive to vasoconstrict. In this issue of The Journal of PhysiologyVogiatzis et al. (2009) reveal that intercostal blood flow is lower during exercise than when the same level of ventilation is maintained in the absence of limb movement. Thus, in contrast to the work of Harms et al. (1997), these findings suggest that blood flow is controlled in a similar fashion to other muscles, with no evidence of a priority over limb muscles. However, it remains to be established, as stated by the authors, whether the primary respiratory muscle, the diaphragm, can maintain blood flow during maximal whole body exercise. Indeed, there are animal studies that suggest that blood flow to the diaphragm is less affected by sympathetic stimulation than other skeletal muscles. Therefore, in light of the prior inference that perhaps when faced with the choice between moving and breathing the choice would be to secure breathing. It appears, at least for this important component of the respiratory muscles, humble pie is on the menu for now.