What is the central question of this study? Can near-infrared spectroscopy (NIRS)-derived post-occlusion tissue oxygen saturation recovery kinetics be used to study age-related impairments in microvascular function? What is the main finding and its importance? Using a previously established 5 min cuff occlusion protocol, we found that NIRS-derived indices of microvascular function were markedly reduced in elderly compared with young participants. However, when we controlled for the absolute level of vasodilatory stimulus and matched the tissue desaturation level between groups, we found similar responses in young and elderly participants. Overall, these data highlight the important role NIRS can serve in clinical vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols. Near-infrared spectroscopy (NIRS) has emerged as a promising tool to evaluate vascular reactivity in vivo. Whether this approach can be used to assess age-related impairments in microvascular function has not been tested. Tissue oxygen saturation (StO2) post-occlusion recovery kinetics were measured in two distinct age groups (<35 and >65 years of age) using NIRS placed over the flexor digitorum profundus. Key end-points included the following: (i) the desaturation rate during cuff occlusion; (ii) the lowest StO2 value obtained during ischaemia (StO2min); (iii) StO2 reperfusion rate; (iv) the highest StO2 value reached after cuff release (StO2max); and (v) the reactive hyperaemia area under the curve (AUC). At first, using a conventional 5 min cuff occlusion protocol, the elderly participants achieved a much slower rate of oxygen recovery (1.5 ± 0.2 versus 2.5 ± 0.2% s ), lower StO2max (85.2 ± 2.9 versus 92.3 ± 1.5%) and lower reactive hyperaemia AUC (2651.8 ± 307.0 versus 4940.0 ± 375.8% s ). However, owing to a lower skeletal muscle resting metabolic rate, StO2min was also significantly attenuated in the elderly participants compared with the young control subjects (55.7 ± 3.5 versus 41.0 ± 3.4%), resulting in a much lower ischaemic stimulus. To account for this important difference between groups, we then matched the level of tissue ischaemia in a subset of young healthy participants by reducing the cuff occlusion protocol to 3 min. Remarkably, when we controlled for tissue ischaemia, we observed no differences in any of the hyperaemic end-points between the young and elderly participants. These data highlight the important role NIRS can serve in vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.

Age is the greatest risk factor for chronic disease and is associated with a marked decline in functional capacity and quality of life. A key factor contributing to loss of function in older adults is the decline in skeletal muscle function. While the exact mechanism(s) remains incompletely understood, age‐related mitochondrial dysfunction is thought to play a major role. To explore this question further, we studied 15 independently living seniors (age: 72 ± 5 years; m/f: 4/11; BMI: 27.6 ± 5.9) and 17 young volunteers (age: 25 ± 4 years; m/f: 8/9; BMI: 24.0 ± 3.3). Skeletal muscle oxidative function was measured in forearm muscle from the recovery kinetics of muscle oxygen consumption using near‐infrared spectroscopy (NIRS). Muscle oxygen consumption was calculated as the slope of change in hemoglobin saturation during a series of rapid, supra‐systolic arterial cuff occlusions following a brief bout of exercise. Aging was associated with a significant prolongation of the time constant of oxidative recovery following exercise (51.8 ± 5.4 sec vs. 37.1 ± 2.1 sec, P = 0.04, old vs. young, respectively). This finding suggests an overall reduction in mitochondrial function with age in nonlocomotor skeletal muscle. That these data were obtained using NIRS holds great promise in gerontology for quantitative assessment of skeletal muscle oxidative function at the bed side or clinic.

Near‐infrared diffuse correlation spectroscopy (DCS) is an emerging technique for non‐invasive measurement of local muscle blood flow at the microvascular level. We have previously shown excellent agreement between single wavelength DCS and Doppler ultrasound of the brachial artery during rhythmic handgrip exercise, supporting the role of DCS in exercise physiology. Here, we report novel DCS data from our lab, incorporating two‐different wavelengths (785 nm and 852 nm), allowing for direct assessment of microvascular perfusion, together with oxyhemoglobin and deoxyhemoglobin. To‐date, we have studied eight individuals (male/female: 3/5, mean: age 48±22 (range: 22–76 years), height 170±8 cm, and weight 75±12 kg). Subjects were instrumented with the DCS probe located over the belly of the flexor digitorum profundus. Duplex ultrasound of the brachial artery was also performed as a secondary measure of skeletal muscle blood flow. Each subject performed two bouts of rhythmic hand grip exercise at 20% of their maximum voluntary contraction (MVC). Each exercise bout was preceded by a standardized resting baseline, and each period of data collection was separated by at least 10 minutes of rest. Data from each round of data collection were averaged. As reported previously using our single wavelength DCS device, blood flow index (BFI, the primary output from DCS) increased significantly (119±37%) with exercise. We also observed a −1.9±1.1% change in oxyhemoglobin and 21.8±10.0% change in deoxyhemoglobin resulting in a −5.9±2.6% change in tissue saturation with exercise. As a result, relative muscle oxygen consumption (rmVO2) increased by 160.2±55.4%. The novelty of this new approach is best illustrated by a case‐comparison between two subjects, who performed similar absolute (11 vs 10 kg) and relative work (20%), and yet achieved disparate levels of oxygen utilization during exercise (ΔrmO2 = 307% vs. 214%, Case A vs. Case B respectively). This difference appears to be explained predominantly by muscle oxygen extraction as both brachial artery blood flow and microvascular perfusion (by DCS) were similar in both subjects. In contrast, Case A exhibited a much greater change in StO2 (−17.8%) compared to Case B, whose StO2 more closely mirrored the group average (−6.8%). To help interpret these results, we evaluated skeletal muscle oxidative capacity in both subjects using an established NIRS‐based cuff occlusion protocol (Rosenberry et al. 2018. JoVE). Remarkably, these additional data corroborated our assumptions, showing a muscle oxygen consumption recovery time of 34 seconds in Case A and 93 seconds in Case B. Taken together, these data establish strong proof‐of‐concept that dual wavelength DCS can provide important mechanistic insight into the determinants of oxygen consumption. Extending these findings to patients with exercise intolerance (e.g. heart failure with preserved or reduced ejection fraction) may provide important therapeutic insight.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.