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• W2802087616 abstract "ViewpointCommentaries on Viewpoint: Principles, insights, and potential pitfalls of the noninvasive determination of muscle oxidative capacity by near-infrared spectroscopyPublished Online:24 Jan 2018https://doi.org/10.1152/japplphysiol.00857.2017MoreSectionsPDF (90 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat COMMENTARY ON VIEWPOINTSusie Chung and Michael D. Nelson.Author AffiliationsUniversity of Texas at Arlington.to the editor: In their Viewpoint, Adami and Rossiter (1) eloquently explore the strengths and weaknesses of combining near-infrared spectroscopy (NIRS) with repetitive postexercise arterial cuff occlusions to measure skeletal muscle oxidative capacity in vivo. Before the advent of this technique, the assessment of mitochondrial function was limited to invasive muscle biopsies and/or expensive and time-consuming magnetic resonance spectroscopy (MRS) techniques. Now, clinicians and researchers alike have a robust, high-throughput clinical platform to noninvasively assess muscle oxidative capacity across a wide range of muscles and disease states. That this approach is easily transportable and relatively low cost opens new possibilities for bedside medicine, clinical decision making, and incorporation into large multicenter clinical trials. However, this increased emphasis on clinical populations also emphasizes the need for future technology development to overcome the well-established limitations of NIRS with regards to limb adiposity (2). While Adami and Rossiter appropriately highlight the relatively large test-retest variability with this technique compared with the differences often observed between health and disease, it is important to emphasize that this variability is similar to that achieved with MRS (5) or muscle biopsies (4). This does highlight the importance of careful experimental/clinical design, however. Indeed, over 40% of the investigations referenced in this Viewpoint studied locomotor muscle groups, which are highly dependent on physical activity level (3). Targeting nonlocomotor muscle groups should help limit within-group variability. With these considerations in mind, we believe NIRS-derived muscle oxidative capacity assessments hold great promise in clinical translational medicine.REFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Ferrari M, Mottola L, Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 29: 463–487, 2004. doi:10.1139/h04-031. Crossref | PubMed | Google Scholar3. Larsen RG, Callahan DM, Foulis SA, Kent-Braun JA. Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior. Appl Physiol Nutr Metab 37: 88–99, 2012. doi:10.1139/h11-135. Crossref | PubMed | ISI | Google Scholar4. Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol 592: 3231–3241, 2014. doi:10.1113/jphysiol.2014.274456. Crossref | PubMed | ISI | Google Scholar5. Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115: 1757–1766, 2013. doi:10.1152/japplphysiol.00835.2013. Link | ISI | Google ScholarREFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Ferrari M, Mottola L, Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 29: 463–487, 2004. doi:10.1139/h04-031. Crossref | PubMed | Google Scholar3. Larsen RG, Callahan DM, Foulis SA, Kent-Braun JA. Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior. Appl Physiol Nutr Metab 37: 88–99, 2012. doi:10.1139/h11-135. Crossref | PubMed | ISI | Google Scholar4. Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol 592: 3231–3241, 2014. doi:10.1113/jphysiol.2014.274456. Crossref | PubMed | ISI | Google Scholar5. Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115: 1757–1766, 2013. doi:10.1152/japplphysiol.00835.2013. Link | ISI | Google ScholarAPPLICATION OF IN VITRO OXIDATIVE PHOSPHORYLATION ASSAY TO HUMAN LIMBS USING NEAR-INFRARED SPECTROSCOPYTakafumi Hamaoka.Author AffiliationsTokyo Medical University.to the editor: Adami and Rossiter (1) provide a contemporary viewpoint on the use of near-infrared spectroscopy (NIRS) to determine skeletal muscle oxidative capacity. There are numerous approaches and applications of NIRS to study skeletal muscle (4). The approach to evaluate muscle oxidative capacity evolved from observations of changes in muscle oxygenation in response to ischemia. Because continuous wavelength NIRS does not provide the absolute value of muscle oxygenation due to undetermined optical path lengths, a physiological calibration was adopted using ischemia to define a scale oxygen levels from near zero to near 100% (3). It was observed that the initial rate of deoxygenation after muscle contractions was greater than that of resting conditions, which reminded me (Hamaoka) of the in vitro assays of mitochondrial oxidative phosphorylation reported by Chance and Williams (2). They showed oxygen tension declined more rapidly under the conditions of higher (state 3) mitochondrial respiration (2). It was felt that the results in vitro should apply in vivo. This hypothesis was validated using brief arterial occlusions and comparing rates of muscle deoxygenation with NIRS to rates of change of ADP and phosphocreatine (PCr) using 31phosphorus magnetic resonance spectroscopy (3). Later, consecutive brief arterial occlusions were applied during the recovery phase after muscle contractions. The rate of recovery for muscle oxygen consumption was validated with comparisons to the rate of recovery for PCr (5). It is an honor to witness the growth of the original concept and methodology for measuring muscle oxidative rate or capacity, and its application to clinical settings. The author acknowledges Dr. Kevin McCully for the stimulating discussions that contributed to the ideas presented in this commentary.REFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217: 383–393, 1955. Crossref | PubMed | ISI | Google Scholar3. Hamaoka T, Iwane H, Shimomitsu T, Katsumura T, Murase N, Nishio S, Osada T, Kurosawa Y, Chance B. Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy. J Appl Physiol (1985) 81: 1410–1417, 1996. doi:10.1152/jappl.1996.81.3.1410. Link | ISI | Google Scholar4. Hamaoka T, McCully KK, Quaresima V, Yamamoto K, Chance B. Near-infrared spectroscopy/imaging for monitoring muscle oxygenation and oxidative metabolism in healthy and diseased humans. J Biomed Opt 12: 062105, 2007. doi:10.1117/1.2805437. Crossref | PubMed | ISI | Google Scholar5. Nagasawa T, Hamaoka T, Sako T, Murakami M, Kime R, Homma T, Ueda C, Ichimura S, Katsumura T. A practical indicator of muscle oxidative capacity determined by recovery of muscle O2 consumption using NIR spectroscopy. Eur J Sport Sci 3: 1–10, 2003. doi:10.1080/17461390300073207.Crossref | Google ScholarREFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217: 383–393, 1955. Crossref | PubMed | ISI | Google Scholar3. Hamaoka T, Iwane H, Shimomitsu T, Katsumura T, Murase N, Nishio S, Osada T, Kurosawa Y, Chance B. Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy. J Appl Physiol (1985) 81: 1410–1417, 1996. doi:10.1152/jappl.1996.81.3.1410. Link | ISI | Google Scholar4. Hamaoka T, McCully KK, Quaresima V, Yamamoto K, Chance B. Near-infrared spectroscopy/imaging for monitoring muscle oxygenation and oxidative metabolism in healthy and diseased humans. J Biomed Opt 12: 062105, 2007. doi:10.1117/1.2805437. Crossref | PubMed | ISI | Google Scholar5. Nagasawa T, Hamaoka T, Sako T, Murakami M, Kime R, Homma T, Ueda C, Ichimura S, Katsumura T. A practical indicator of muscle oxidative capacity determined by recovery of muscle O2 consumption using NIR spectroscopy. Eur J Sport Sci 3: 1–10, 2003. doi:10.1080/17461390300073207.Crossref | Google ScholarVALIDATION OF NEAR-INFRARED SPECTROSCOPY METHODOLOGY TO ASSESS SKELETAL MUSCLE OXIDATIVE CAPACITY TO THAT OF HIGH-RESOLUTION RESPIROMETRIC METHODOLOGY SHOULD EASE SOME CONCERNSRobert A. Jacobs, James Pearson, and Andrew W. Subudhi.Author AffiliationsUniversity of Colorado.to the editor: Adami and Rossiter (1) highlight important considerations when assessing skeletal muscle oxidative capacity (OXPHOSSM) with near-infrared spectroscopy (NIRS). Their two primary concerns 1) achieving maximal activation of oxidative enzymes and 2) potential limitations of oxygen delivery to muscle, were addressed when NIRS-derived OXPHOSSM was validated to in situ measures of OXPHOSSM via high-resolution respirometry (HRR) (5). The HRR protocol utilized saturating substrate concentrations and reported strong correlations (Pearson's r = 0.61–0.74, P < 0.01) between HRR- and NIRS-derived OXPHOSSM (5). Cellular respiration coordinates and integrates the interaction of many enzymes to function collectively within a system, often below their individual maximal enzymatic velocities; i.e., HRR derived cytochrome c oxidase activity, alone, exceeds complementary measures of OXPHOSSM (4). Thus valid measures of OXPHOSSM require maximal activation of respiratory pathways opposed to individual enzymes. Additionally, HRR uses saturating concentrations of oxygen such that observed variations across measurements reflect differences in mitochondrial function per se versus inconsistent fiber permeabilization and attendant diffusive disparities. Correlation between NIRS- and HRR-derived OXPHOSSM suggests that oxygen availability is not problematic when assessing OXPHOSSM via NIRS in healthy subjects. Moreover, oxygen delivery is a component of in vivo respiratory capacity. If oxygen availability becomes limiting, as observed in certain diseased states such as COPD, then delivery dictates OXPHOSSM and respiratory capacity adapts accordingly (3). We appreciate the primary concerns raised by Adami and Rossiter; however, we contend that controlling the influence of skin blood flow and subcutaneous adipose thickness are more significant considerations when assessing OXPHOSSM via NIRS (2).REFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Davis SL, Fadel PJ, Cui J, Thomas GD, Crandall CG. Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress. J Appl Physiol (1985) 100: 221–224, 2006. doi:10.1152/japplphysiol.00867.2005. Link | ISI | Google Scholar3. Gifford JR, Trinity JD, Layec G, Garten RS, Park SY, Rossman MJ, Larsen S, Dela F, Richardson RS. Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration. J Appl Physiol (1985) 119: 882–888, 2015. doi:10.1152/japplphysiol.00460.2015. Link | ISI | Google Scholar4. Jacobs RA, Flück D, Bonne TC, Bürgi S, Christensen PM, Toigo M, Lundby C. Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function. J Appl Physiol (1985) 115: 785–793, 2013. doi:10.1152/japplphysiol.00445.2013. Link | ISI | Google Scholar5. Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol 592: 3231–3241, 2014. doi:10.1113/jphysiol.2014.274456. Crossref | PubMed | ISI | Google ScholarREFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Davis SL, Fadel PJ, Cui J, Thomas GD, Crandall CG. Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress. J Appl Physiol (1985) 100: 221–224, 2006. doi:10.1152/japplphysiol.00867.2005. Link | ISI | Google Scholar3. Gifford JR, Trinity JD, Layec G, Garten RS, Park SY, Rossman MJ, Larsen S, Dela F, Richardson RS. Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration. J Appl Physiol (1985) 119: 882–888, 2015. doi:10.1152/japplphysiol.00460.2015. Link | ISI | Google Scholar4. Jacobs RA, Flück D, Bonne TC, Bürgi S, Christensen PM, Toigo M, Lundby C. Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function. J Appl Physiol (1985) 115: 785–793, 2013. doi:10.1152/japplphysiol.00445.2013. Link | ISI | Google Scholar5. Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol 592: 3231–3241, 2014. doi:10.1113/jphysiol.2014.274456. Crossref | PubMed | ISI | Google ScholarCOULD NIRS BE AS UBIQUITOUS AS THE METABOLIC CART IN EXERCISE PHYSIOLOGY LABORATORIES?Nathan T. Jenkins.Author AffiliationsUniversity of Georgia.to the editor: Until about the 1970s, the routine measurement of oxygen uptake (V̇o2) was limited to a small field of niche experts who specialized in work physiology. This was likely attributable to the complicated nature of the methodology; although elegant in its underlying principles, the Douglas bag technique (2) is cumbersome in its execution and highly subject to user expertise. Gradually, through technological advances and methodological simplifications (5), it has become routine for exercise physiology laboratories to have the ability to measure V̇o2max. Although speculative, it seems possible that an analogous evolution is underway for the assessment of muscle oxidative capacity. Due to the limitations of traditional methods (biopsy and 31P MRS) (1), mitochondrial capacity assessment has been traditionally confined to laboratories that specialize almost exclusively in muscle mitochondrial biology. But recent advances (3) in near-infrared spectroscopy (NIRS)-based methods could enable more investigators to incorporate assessments of mitochondrial capacity into their studies in a complementary manner to their primary focus. For example, our recent study (4) included a NIRS-based assessment of cycling training-induced changes in quadriceps oxidative capacity. Our NIRS measurement served as a validation of our training stimulus; i.e., was the training sufficient to increase muscle oxidative capacity, when other novel (vascular) markers may or may not have changed in response to training. Although further advances in the NIRS method are still needed, it is exciting to consider the novelty and innovation that could result from the collective field’s expanded ability to include assessments of mitochondrial capacity into integrative research projects. The author acknowledges Dr. Kevin McCully for the stimulating discussions that contributed to the ideas presented in this commentary.REFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Douglas CG. A method for determining the total respiratory exchange in man. J Physiol 42: xvii–xxii, 1911.Google Scholar3. Ryan TE, Erickson ML, Brizendine JT, Young H-J, McCully KK. Noninvasive evaluation of skeletal muscle mitochondrial capacity with near-infrared spectroscopy: correcting for blood volume changes. J Appl Physiol (1985) 113: 175–183, 2012. doi:10.1152/japplphysiol.00319.2012. Link | ISI | Google Scholar4. Shill DD, Southern WM, Willingham TB, Lansford KA, McCully KK, Jenkins NT. Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake. J Physiol 594: 7005–7014, 2016. doi:10.1113/JP272491. Crossref | PubMed | ISI | Google Scholar5. Wilmore JH, Costill DL. Semiautomated systems approach to the assessment of oxygen uptake during exercise. J Appl Physiol 36: 618–620, 1974. doi:10.1152/jappl.1974.36.5.618. Link | ISI | Google ScholarREFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Douglas CG. A method for determining the total respiratory exchange in man. J Physiol 42: xvii–xxii, 1911.Google Scholar3. Ryan TE, Erickson ML, Brizendine JT, Young H-J, McCully KK. Noninvasive evaluation of skeletal muscle mitochondrial capacity with near-infrared spectroscopy: correcting for blood volume changes. J Appl Physiol (1985) 113: 175–183, 2012. doi:10.1152/japplphysiol.00319.2012. Link | ISI | Google Scholar4. Shill DD, Southern WM, Willingham TB, Lansford KA, McCully KK, Jenkins NT. Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake. J Physiol 594: 7005–7014, 2016. doi:10.1113/JP272491. Crossref | PubMed | ISI | Google Scholar5. Wilmore JH, Costill DL. Semiautomated systems approach to the assessment of oxygen uptake during exercise. J Appl Physiol 36: 618–620, 1974. doi:10.1152/jappl.1974.36.5.618. Link | ISI | Google ScholarCOMMENTARY ON VIEWPOINTMiles F. Bartlett, Liam F. Fitzgerald, Julia D. Miehm, and Jane A. Kent.Author AffiliationsUniversity of Massachusetts Amherst.to the editor: Muscle oxidative capacity can be defined as the tissue’s maximum rate for oxidative phosphorylation, a process that takes place in the mitochondria and is supported by the delivery of oxygen and substrate. In their Viewpoint, Adami and Rossiter (1) discuss the potential for near-infrared spectroscopy (NIRS) to measure muscle oxidative capacity in vivo. Support for this viewpoint includes the associations between NIRS variables and both respirometry and 31-phosphorus magnetic resonance spectroscopy (MRS; 4, 5) measures, the current gold standards for in vitro and in vivo assessment of oxidative capacity, respectively (2). Indeed, with the recent development of frequency-domain NIRS systems, many of the technical problems related to this methodology appear to have been addressed. It is worth bearing in mind, however, that each of these methods differs in the physiological compartment being sampled. In the case of respirometry, oxidative capacity can be determined directly in isolated mitochondria, single muscle fibers, and fiber bundles (2, 3), but in the absence of full physiological conditions. In contrast, the in vivo measures obtained by MRS and NIRS reflect changes in the cytosol and vasculature, respectively. Furthermore, MRS is used to quantify oxidative ATP production in the volume of interest, whereas NIRS evaluates changes in oxygen saturation of hemoglobin (and to some extent, myoglobin) and therefore reflects oxygen consumption rather than oxidative ATP production. Thus, selection of the appropriate tool for evaluating muscle oxidative capacity will depend on instrumentation quality, the research question to be addressed, and an understanding of all methodological assumptions and constraints.REFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Kent JA, Fitzgerald LF. In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use. J Appl Physiol (1985) 121: 996–1003, 2016. doi:10.1152/japplphysiol.00583.2016. Link | ISI | Google Scholar3. Lanza IR, Bhagra S, Nair KS, Port JD. Measurement of human skeletal muscle oxidative capacity by 31P-MR spectroscopy: a cross-validation with in vitro measurements. J Magn Reson Imaging 34: 1143–1150, 2011. doi:10.1002/jmri.22733. Crossref | PubMed | ISI | Google Scholar4. Ryan TE, Brophy P, Lin C-T, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol 592: 3231–3241, 2014. doi:10.1113/jphysiol.2014.274456. Crossref | PubMed | ISI | Google Scholar5. Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115: 1757–1766, 2013. doi:10.1152/japplphysiol.00835.2013. Link | ISI | Google ScholarREFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Kent JA, Fitzgerald LF. In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use. J Appl Physiol (1985) 121: 996–1003, 2016. doi:10.1152/japplphysiol.00583.2016. Link | ISI | Google Scholar3. Lanza IR, Bhagra S, Nair KS, Port JD. Measurement of human skeletal muscle oxidative capacity by 31P-MR spectroscopy: a cross-validation with in vitro measurements. J Magn Reson Imaging 34: 1143–1150, 2011. doi:10.1002/jmri.22733. Crossref | PubMed | ISI | Google Scholar4. Ryan TE, Brophy P, Lin C-T, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol 592: 3231–3241, 2014. doi:10.1113/jphysiol.2014.274456. Crossref | PubMed | ISI | Google Scholar5. Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115: 1757–1766, 2013. doi:10.1152/japplphysiol.00835.2013. Link | ISI | Google ScholarUSE OF AUTOMATION SOFTWARE FOR INCREASED STANDARDIZATION, ACCURACY, AND PRECISIONAdam A. Lucero,1 David S. Rowlands,1 and Lee Stoner12.Author Affiliations1Massey University.2University of North Carolina at Chapel Hill.to the editor: Near infrared spectroscopy (NIRS) permits the assessment of skeletal muscle mitochondrial oxidative capacity in situ. In situ, mitochondrial respiration is dependent on several physiological systems operating within a closed environment, i.e., microvascular perfusion of blood, tissue oxygen extraction, and terminal respiratory chain oxidative coupling. Therefore, NIRS, which has been validated against phosphorus-magnetic resonance spectroscopy based assessments (2), measures a composite of mitochondrial respiratory capacity. However, NIRS procedures require substantial operator expertise, and further technological innovation is necessary to improve measurement precision (reliability) and accuracy (validity). First, with respect to the former, we have found that rapid (<1.0 s) occlusion improves reliability (3). Second, our custom automated analysis software enables immediate outcome feedback and retesting as required. Lastly, we plan to develop automation software to control arterial occlusions based on real-time NIRS tissue oxygen saturation (StO2) feedback. Accurate assessment of mitochondrial oxidative capacity is dependent on maximal activation of mitochondrial oxidative enzymes while maintaining adequate StO2 so as to not alter phosphocreatine recovery kinetics (1). This can be achieved by using a 5-min arterial occlusion to determine the minimum and subsequent maximum StO2. Then, during the oxidative capacity test, the automation software will prevent full StO2 depletion during the occlusion, then ensure adequate recovery following occlusion based on real-time StO2 feedback. In summary, automation software, for arterial occlusion control and outcome analysis, will limit operator bias and assist with measurement standardization, thereby enhancing measurement accuracy and precision.REFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Lucero AA, Addae G, Lawrence W, Neway B, Credeur DP, Faulkner J, Rowlands D, Stoner L. Reliability of muscle blood flow and oxygen consumption response from exercise using near-infrared spectroscopy. Exp Physiol 103: 90–100, 2018. doi:10.1113/EP086537.Crossref | ISI | Google Scholar3. Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115: 1757–1766, 2013. doi:10.1152/japplphysiol.00835.2013. Link | ISI | Google ScholarREFERENCES1. Adami A, Rossiter HB. Viewpoint: Principles, insights, and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy. J Appl Physiol. doi:10.1152/japplphysiol.00445.2017.Link | ISI | Google Scholar2. Lucero AA, Addae G, Lawrence W, Neway B, Credeur DP, Faulkner J, Rowlands D, Stoner L. Reliability of muscle blood flow and oxygen consumption response from exercise using near-infrared spectroscopy. Exp Physiol 103: 90–100, 2018. doi:10.1113/EP086537.Crossref | ISI | Google Scholar3. Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985) 115: 1757–1766, 2013. doi:10.1152/japplphysiol.00835.2013. Link | ISI | Google ScholarMITOCHONDRIAL CAPACITY: WHAT DOES IT MEAN?Kevin K. McCully, and Jarrod Call.Author AffiliationsUniversity of Georgia.to the editor: Adami and Rossiter (1) present an emerging method for evaluating skeletal muscle mitochondrial capacity. A key to these measurements is the understanding of what mitochondrial capacity means and how it can be used to evaluate skeletal muscle. The near-infrared derived recovery rate constant reflects the metabolic rate with maximal substrate availability analogous to Michaelis-Menten enzyme kinetics. This can be inferred to be the maximal metabolic rate of the muscle (5). Because the NIRS measurements are performed on intact skeletal muscle in the body, the rate constant reflects structurally intact skeletal muscle. This is important because of the increasing realization that structure of mitochondrial in intact skeletal muscle is both dynamic and important in determining its function (2). The key question then is how to interpret the measurements of NIRS-derived mitochondrial capacity. A simplified approach is to consider mitochondrial capacity to be a combination of mitochondrial function and mitochondrial volume. Recent studies employing innovative approaches to gain mechanistic insight have shown that exercise training can increase mitochondrial volume independent of biogenesis (3) and describe the pathology associated with aging leading to decreases in mitochondrial capacity (4). Considering this, the advantage of the NIRS measured mitochondrial capacity is that it reflects the oxidative metabolic capacity of the intact skeletal muscle under the operating conditions in the intact organism. The limitation is that NIRS measured mitochondrial capacity does not provide mechanistic interpretations for the changes that underlie changes in mitochondrial capacity.REFERENCE" @default.
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• W2802087616 doi "https://doi.org/10.1152/japplphysiol.00857.2017" @default.
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