Response to: control of muscle exercise hyperaemia: are the mechanisms found in transition?

Abstract

I would like to thank Drs Poole and Behnke for their interest in our review and for initiating a scientific discussion (Poole & Behnke, 2015). If the mechanisms regulating exercise hyperaemia are to be identified in the transition from rest to exercise, it requires that the regulatory mechanisms at the onset of exercise and during ‘steady-state’ exercise conditions are the same. Our knowledge of the regulatory mechanisms during both conditions is incomplete, but it is clear that metabolic processes are too slow to account for the initial blood flow response. It therefore seems likely that the mechanism(s) initiating exercise hyperaemia are, at least in part, different from the ones that sustain it (Clifford & Hellsten, 2004). Thus, although the mechanisms governing the initial rise in exercise hyperaemia are intriguing and important, they do not necessarily provide insight into the regulatory mechanism(s) during ‘steady-state’ conditions or vice versa. It is postulated by Drs Poole and Behnke that ‘steady-state’ exercise hyperaemia for a given work rate is similar in sedentary people, elite athletes and patients and, based on this assumption, the authors make the bald statement that ‘steady-state’ blood flows may not be particularly insightful for resolving the control mechanisms. However, there is evidence demonstrating that exercise hyperaemia and heterogeneity are affected by training status (Saltin et al. 1976; Kalliokoski et al. 2001) and ageing (Proctor & Parker, 2006) as well as in disease states (Sullivan et al. 1989; Nyberg et al. 2012b). Moreover, when combined with other measurements (such as blood samples, microdialysis and/or biopsies), differences in metabolism and regulatory mechanisms can be revealed despite a similar exercise hyperaemia (Mortensen et al. 2012; Nyberg et al. 2012a). Based on the assumption that exercise hyperaemia is similar among populations, Drs Poole and Behnke suggest it is the oxygen uptake () kinetics that are insightful for explaining differences in exercise tolerance between an athlete and a heart failure patient, but neglect the importance of O2 delivery and its impact on muscle metabolism when the fatigue and thus exercise intolerance become apparent. In this light, it is critical to remark that the fatigue processes during walking/running are temporally more closely related to than the kinetics. Understanding why exercise hyperaemia and consequently O2 delivery are impaired in heart failure is key to understanding O2 utilization and exercise intolerance (Esposito et al. 2010). Our human studies have often been inspired by results obtained in advanced animal studies, and we have turned to animal models when limited in our human models. That said, there are clear anatomical and physiological differences between animals and humans that are important to cardiovascular regulation, and one should be very careful before extrapolating findings in animals to humans (see Rowell, 2007). It is my opinion that observations from animal studies should never be seen as definitive before they have been confirmed in humans. Drs Poole and Behnke indicate that the mechanisms governing exercise hyperaemia are different between populations, but the same holds true for species. Skeletal muscle perfusion rates can reach similar values in animals and humans, but the size of the heart in relation to body weight is much smaller in humans. How does this affect the kinetics and the contribution of O2-dependent and independent limitations to O2 utilization? It is clearly relevant to relate not only findings in humans to findings in animals, but also the other way around. I agree with Drs Poole and Behnke that a blend of animal and human investigations is the key to new insight into the regulatory mechanisms in health and how they are altered in disease states. I would like to reassure Drs Poole and Behnke that if we had been asked to write a more extensive review, we would certainly have included more animal work, multiple exercise conditions (for example transition, low and high intensities) and populations (for example, training status and patients). However, we were asked to write a short review on the Scandinavian perspective of blood flow regulation, and this is why our review is limited to the mechanisms regulating ‘steady-state’ exercise hyperaemia in healthy humans. None declared.