Work

Response

Year: 2015

Type: article

Abstract: Dear Editor-in-Chief, We thank Murias and Paterson (4) for their interest in our work and for raising two important questions about our recent publication (6) in Medicine & Science in Sports & Exercise. This article provides evidence that deoxygenated myoglobin (deoxy-Mb) accumulation, assessed in the muscles of the lower leg, lags behind phosphocreatine (PCr) breakdown during moderate-intensity and heavy-intensity plantarflexion exercise in humans (6). The first concern is whether the fitting methods used to quantify deoxy-Mb and PCr kinetics influenced the interpretation that deoxy-Mb desaturation lags behind PCr breakdown. The second question is whether a V˙O2 time constant greater than 20 s resides beyond a “tipping point” for V˙O2 onset kinetics, where mitochondrial O2 delivery becomes limiting to the kinetics of oxidative phosphorylation. To address the first concern, naturally, we agree that selection of the appropriate fitting methods is crucial to the quantitation, statistical comparison, and interpretation of deoxy-Mb and PCr kinetic responses. Indeed, we went to great lengths to select modeling procedures that produce model fits that best reflect the physiologic processes underlying the deoxy-Mb and PCr responses. The decision to constrain PCr fit to begin at exercise onset was based on a feature of the underlying physiology and on the data. Specifically, creatine kinase reaction is extremely rapid; thus, PCr buffers the immediate energy demands of muscle contraction (1). Therefore, a model that allows PCr breakdown to begin before muscle contraction commences has little physiologic justification. Furthermore, in this study, the mean time delay, using an unconstrained fit, could not be distinguished from exercise onset at 120 s (moderate, 116 ± 5 s, P = 0.11; heavy, 117 ± 6 s, P = 0.18). Deoxy-Mb response was fit as described in a study by DeLorey et al. (2), where the onset time of deoxy-Mb increase (above baseline fluctuations) was identified and the kinetics was determined from a fitting window projecting forward from that point. Therefore, the reported deoxy-Mb time constant should be free from the influence of the early delay-like phase and should be dependent on the exponent-like region of the response. That said, to reassure the journal’s readership, here we provide a figure that better documents the group mean deoxy-Mb and PCr kinetic responses during the early transient period [Fig. 1; redrawn from Fig. 1 in Richardson et al. (6)]. The data, averaged across all participants, clearly illustrate that PCr kinetics is more rapid than deoxy-Mb kinetics during both moderate-intensity and heavy-intensity exercises and, of importance, this interpretation is unencumbered by concerns regarding fitting method selection.FIGURE 1: Group mean (n = 6) PCr breakdown and deoxy-Mb increase across the rest-to-exercise transition for moderate-intensity (60% of the work rate associated with isolated muscle aerobic capacity) and high-intensity (80% peak work rate) plantarflexion exercise. Data are normalized to the percentage of end-exercise values. The figure is redrawn from Figure 1 in Richardson et al. (6) to illustrate the difference in PCr and deoxy-Mb kinetics during the first minute of contractions. Error bars are omitted for clarity [see Richardson et al. (6)].The second concern raised by Murias and Paterson (4) regarding the proposed V˙O2 onset kinetics tipping point, where mitochondrial O2 delivery becomes limiting to the kinetics of oxidative phosphorylation, certainly provides a useful conceptual framework for examining such interactions. Murias et al. (5) suggested a value for the tipping point (V˙O2 time constant τ ∼20 s) that delimits an O2 delivery–dependent zone from an O2 delivery–independent zone based on a series of cycle ergometry experiments. This value is likely highly specific for (a) the exercise modality employed (e.g., double-leg cycling, plantarflexion exercise, etc.) and (b) the relative balance between the respiratory capacity of the muscle studied and the cardiovascular capacity to transport O2 to the active muscle mass. Therefore, although we acknowledge the view that V˙O2 onset kinetics appears to be O2 delivery–limited when τ V˙O2 is slower than 20 s during cycling exercise in young adults (5), this does not necessarily apply to our experimental paradigm. Because skeletal muscles in the lower limbs exhibit a mitochondrial content relatively similar to that of the rest of the muscles employed during cycling exercise (3), the use of a small muscle mass exercise modality (single-leg plantarflexion) in our study (6) would likely have limited the influence of O2 availability on the exercising muscle, thus shifting the tipping point to a higher value compared to a large muscle mass exercise such as cycling. Therefore, despite a calculated τ > 30 s for PCr and deoxy-Mb, due to very different experimental paradigms, our finding that O2 supply did not limit the adjustment of oxidative phosphorylation may not be an overstatement and does not necessarily conflict with the modified tipping point concept proposed by Murias et al. (5). Russell S. Richardson Division of Geriatrics Department of Medicine University of Utah Salt Lake City, UT Department of Exercise and Sport Science University of Utah Salt Lake City, UT Geriatric Research Education, and Clinical Center Salt Lake City VA Medical Center Salt Lake City, UT Claire Wary Institut of Myology Paris, FRANCE CEA, I2BM, MIRcen IdM NMR Laboratory Paris, FRANCE D. Walter Wray Division of Geriatrics Department of Medicine University of Utah Salt Lake City, UT Department of Exercise and Sport Science University of Utah Salt Lake City, UT Geriatric Research Education, and Clinical Center Salt Lake City VA Medical Center Salt Lake City, UT Jan Hoff Faculty of Medicine Norwegian University of Science and Technology Trondheim, NORWAY Harry B. Rossiter Division of Respiratory and Critical Care Physiology, and Medicine Department of Medicine Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance, CA Gwenael Layec Division of Geriatrics Department of Medicine University of Utah Salt Lake City, UT Geriatric Research Education, and Clinical Center Salt Lake City VA Medical Center Salt Lake City, UT Pierre G. Carlier Institut of Myology Paris, FRANCE CEA, I2BM, MIRcen IdM NMR Laboratory Paris, FRANCE

Source: Medicine & Science in Sports & Exercise

DOI: 10.1249/mss.0000000000000739