In response to the recent letter by Antonio Crisafulli

We would like to thank the author of a recent letter for their supportive words about our publication in Experimental Physiology (Lam, Greenhough, Nazari, White, & Bruce, 2019). We agree that some of the findings we made bearcomparison with those made in a previous study led by the author (Crisafulli et al., 2011) and, indeed, earlier studies of a similar design to theirs (Asmussen & Nielsen, 1964; Sargeant, Rouleau, Sutton, & Jones, 1981). In these previous studies, amplification of cardiorespiratory responses was observed during the exercise of muscle groups with occluded circulation, in comparison to free-flowing conditions. These are interesting findings, but a limitation with this design is that it is impossible to determine whether the amplified responses are attributable to: (i) enhanced muscle metaboreflex activity from trapped metabolites; (ii) augmented mechanoreflex activity from the sensitization of polymodal mechanically sensitive afferents (Drew, McIntyre, Ring, & White, 2008; Li & Sinoway, 2002); (iii) the greater central motor drive (central command) required to compensate for the reduced capacity of the ischaemic muscle; or (iv) some complex combination. The advantage of the design used in our recent study is that it isolates the effects of enhanced metaboreflex activity (Lam et al., 2019). This is because we examined cardiorespiratory responses to single-legged cycling exercise with/without postexercise circulatory occlusion (PECO) of the inactive contralateral leg, thereby eliminating potential confounding effects of augmented mechanoreflex or central command. We do not yet understand how this altered afferent information is integrated centrally, such that it drives enhanced responses in ventilation and heart rate, but we can be confident that these amplified responses were a result of increased muscle metaboreflex activation. These findings, of course, contrast with studies using PECO at rest, which classically show that heart rate and ventilation return to baseline levels (e.g. Rowell, Hermansen, & Blackmon, 1976). We were surprised by the criticism of our publication for not discussing the role of the baroreflex in the heart rate response postexercise, because we suggested that it is likely to be attributable to the withdrawal of central command and muscle mechanoreflex activity postexercise, and hence the consequent reactivation of cardiac parasympathetic activity via the baroreflex. Indeed, support for this concept has been established elegantly by studies in which cardiac parasympathetic tone was blocked pharmacologically, demonstrating an incomplete recovery of heart rate during PECO at rest (Fisher et al., 2010). This clearly suggests that the metaboreflex can drive heart rate responses (via increased cardiac sympathetic activity), but it is usually masked by parasympathetic reactivation during resting PECO. We therefore believe that a more noteworthy (and unanswered) question is, why does ventilation classically return to baseline during PECO at rest? Perhaps a role for a ventilatory baroreflex (Heistad, Abboud, Mark, & Schmid, 1975)?