Age‐related microvascular dysfunction: novel insight from near‐infrared spectroscopy

Abstract

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.

Reduced insulin sensitivity in young, normoglycaemic subjects alters microvascular tissue oxygenation during postocclusive reactive hyperaemia

“…Measurement of the sensitivity of STO 2 upslope has been well documented and supported in recent years, because NIRS is a low‐cost, easy‐to‐use methodology and has low test–retest variability both within and between days (McLay et al., ; Rosenberry et al., ; Soares et al., ). Soares et al () found that STO 2 upslope was positively correlated with %FMD of the brachial artery, a measure of cardiovascular health.…”

“…Recent research by Rosenberry et al. () indicated that the STO 2 upslope is likely to be influenced by the magnitude of the stimulus (i.e. the amount of ischaemia associated with cuff occlusion) as measured by the minimal STO 2 .…”

“…those who have a lower minimal STO 2 , have a steeper STO 2 upslope, owing, in part, to the increased number of vasodilating metabolites released during cuff occlusion. Rosenberry et al (2018) indicated that the STO 2 upslope is likely to be influenced by the magnitude of the stimulus (i.e. the amount of ischaemia associated with cuff occlusion) as measured by the minimal STO 2 .…”

“…the STO 2 reperfusion rate [STO 2 upslope (as a percentage per minute)] during PORH}. Research supports that NIRS, as a measure for microvascular responsiveness, is repeatable between trials (McLay, Nederveen, Pogliaghi, Paterson, & Murias, ) and sensitive to factors such as training (Soares, George, Proctor, & Murias, ), occlusion duration (McLay, Gilbertson, Pogliaghi, Paterson, & Murias, ), obesity (Soares & Murias, ), glucose load (Soares, Reimer, Alenezi, Doyle‐Baker, & Murias, ) and age (Rosenberry et al., ). Such findings support that NIRS coupled with PORH is an effective way to measure vascular health and assess the degree of vascular impairment in certain disease states.…”

The association between near‐infrared spectroscopy assessment of microvascular reactivity and flow‐mediated dilation is disrupted in individuals at high risk for cardiovascular disease

“…Thus, properly assessing vascular function within conduit artery and the microvascular circulation is important for prevention, early detection, and monitoring of CVD . In relation to this, the use of near‐infrared spectroscopy (NIRS) combined with vascular occlusion test (VOT) technique (NIRS‐VOT) has been demonstrated to be a useful tool for assessment of microvascular function . This technique evaluates microvascular reactivity by assessing the steepness of the upslope of the muscle oxygen saturation signal (reperfusion slope, % per s), typically following a 5‐min period of limb occlusion .…”