Determinants of Reactive Hyperemia Measured by Near‐Infrared Diffuse Correlation Spectroscopy

Abstract

Recent work has shown that measures of reactive hyperemia (RH) are temporally dissociated when assessed by Doppler ultrasound (i.e. upstream conduit blood flow) and near‐infrared diffuse correlation spectroscopy (NIR‐DCS; a direct measure of microvascular perfusion). To probe the physiological mechanisms underlying these discordant responses, we used Doppler ultrasound (Vivid‐i, GE) and NIR‐DCS (MetaOx, ISS Inc.) to measure RH in 13 healthy young adults (7F, 22.9 ± 3.3 yrs) under varying physiological conditions. First, with the arm at heart level (N), we manipulated the duration of limb ischemia (3 vs 6 min) to assess the impact of the ischemic stimulus. Second, we reduced/increased forearm perfusion pressure (FPP) by positioning the experimental arm above (60°) or below (30°) the heart, and measured RH following 3 min of occlusion. The 6min‐N trial was always conducted first, followed by the three 3‐min trials in randomized order. FPP was measured using finger photoplethysmography, corrected for the hydrostatic distance. For the 6min‐ and 3min‐N trials, resting BA blood flow was not different between conditions; however, baseline NIR‐DCS blood flow index (BFI) was lower during the 6min‐N trial than the 3min‐N trial (0.70 ± 0.40 vs 0.94 ± 0.41 cm2·10−8 AU, p < 0.01). As expected, the magnitude of peak BA blood flow during RH increased with increasing ischemia duration (341.9 ± 94.5 vs 284.9 ± 80.1 mL/min, 6min‐ vs 3min‐N, p = 0.03), as was peak NIR‐DCS derived BFI (3.11 ± 1.3 vs 2.54 ± 0.75 cm2·10−8 AU, p = 0.03). For the arm Above/Below trials, FPP was significantly lower in the Above position compared to Below (76.0 ± 5.4 vs 107.9 ± 5.9 mmHg, p < 0.01). Prior to cuff inflation, raising the arm above the heart also reduced BFI relative to the Below position (0.70 ± 0.26 vs 0.99 ± 0.51 cm2·10−8 AU, p = 0.03), whereas BA blood flow was similar between arm positions (23.4 ± 13.8 vs 32.1 ± 11.2 mL/min, p = 0.12). Following cuff deflation, peak BA blood flow (379.5 ± 143.5 vs 227.0 ± 63.9 mL/min, p < 0.01) and peak BFI (2.98 ± 1.00 vs 1.76 ± 0.59 cm2·10−8 AU, p <0.01) were higher with the arm Below the level of the heart compared to Above. The difference in peak BA blood flow was abolished however, when expressed as a % change from baseline (1198.8 ± 320.7 vs 1260.2 ± 817.8 %, Below vs Above, p = 0.79), whereas the difference in peak BFI was not (360.8 ± 170 vs 259.4 ± 64.8 %, p = 0.03). Remarkably, the RH BFI slope was nearly 3‐fold higher in the Below position compared to Above (0.14 ± 0.08 vs 0.05 ± 0.02, p < 0.01), but much smaller when manipulating the duration of ischemia (0.12 ± 0.04 vs 0.09 ± 0.04 cm2·10−8·s−1 AU, 3min‐ vs 6min‐N, p = 0.02), though this latter observation may have been due to an order effect. In toto, these results support previous findings that RH is dependent on the ischemic stimulus, regardless of the assessment technique, as the peak rates of BA blood flow and BFI were greater in the 6min‐N trial compared to the 3min‐N trial. Alternatively, the rate of microvascular reperfusion (i.e. BFI slope) is less affected by the ischemic stimulus to vasodilate and is instead primarily affected by changes in perfusion pressure, suggesting this measure may offer greater insight into the physiological mechanisms underlying microvascular function and reactive hyperemia.