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Near-infrared diffuse correlation spectroscopy (NIR-DCS) is an optical imaging technique for measuring relative changes in skeletal muscle microvascular perfusion (i.e., fold-change above baseline) during reactive hyperemia testing and exercise and is reported as a blood flow index (BFI). Although it is generally accepted that changes in BFI are primarily driven by changes in muscle perfusion, it is well-known that large, hyperthermia-induced changes in cutaneous blood flow can uncouple this relationship. What remains unknown, is how much of an impact that changes in cutaneous perfusion have on NIR-DCS BFI and estimates of skeletal muscle perfusion under thermoneutral conditions, where changes in cutaneous blood flow are assumed to be relatively low. We therefore used epinephrine-iontophoresis to pharmacologically block changes in cutaneous perfusion throughout a battery of experimental procedures. The data show that: (1) epinephrine-iontophoresis attenuates changes in cutaneous perfusion for up to 4-hours post-treatment, even in the face of significant neural- and local-stimuli, (2) under thermoneutral conditions, cutaneous perfusion does not significantly impact NIR-DCS BFI during reactive hyperemia testing or moderate-intensity exercise, and (3) during passive whole-body heat stress, when cutaneous vasodilation is pronounced, epinephrine-iontophoresis preserves NIR-DCS measures of skeletal muscle BFI during moderate-intensity exercise. Collectively, these data suggest that cutaneous perfusion is unlikely to have a major impact on NIR-DCS estimates of skeletal muscle BFI under thermoneutral conditions, but that epinephrine-iontophoresis can be used to abolish cutaneous contamination of the NIR-DCS BFI signal during studies where skin blood flow may be elevated but skeletal muscle perfusion is of specific interest.

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Post-ischemia reperfusion kinetics are markedly dissociated when comparing the macro- versus microvasculature. We used Doppler ultrasound and near-infrared diffuse correlation spectroscopy (NIR-DCS), an emerging technique for continuously and non-invasively quantifying relative changes in skeletal muscle microvascular perfusion (i.e., Blood Flow Index; or BFI), to measure macro- and microvascular reactive hyperemia (RH) in the non-dominant arm of 16 healthy young adults. First, we manipulated the duration of limb ischemia (3 vs 6 min) with the limb at heart level (neutral, -N). Then, we reduced/increased forearm perfusion pressure (PP) by positioning the arm above (3min-A, 60°) or below (3min-B, 30°) the heart. The major novel findings were two-fold: Changes in the ischemic stimulus similarly affected peak macrovascular (i.e., conduit, mL·min-1) and microvascular (i.e., peak NIR-DCS derived BFI) reperfusion during reactive hyperemia (6min-N>3min-N, p<0.05, both) but did not affect the rate at which microvascular reperfusion occurs (i.e. BFI slope). Second, changing forearm PP predictably affected both peak macro- and microvascular reperfusion during RH (3min-B>N>A, p<0.05, all), as well as the rate at which microvascular reperfusion occurred (BFI Slope; 3min-B>N>A, p<0.05). Together, the data suggest that kinetic differences between macro- and microvascular reperfusion are largely determined by differences in fluid mechanical energy (i.e., pressure, gravitational, and kinetic energies) between the two compartments that work in tandem to restore pressure across the arterial tree following a period of tissue ischemia.

Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48‐h food restriction model to acutely increase myocardial triglyceride (mTG) content – measured by 1H magnetic resonance spectroscopy – in 27 young healthy volunteers (13 men/14 women). Forty‐eight hours of fasting caused a more than 3‐fold increase in mTG content (P < 0.001). Diastolic function – defined as early diastolic circumferential strain rate (CSRd) – was unchanged following the 48‐h fasting intervention, but systolic circumferential strain rate was elevated (P < 0.001), indicative of systolic–diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low‐dose dobutamine (2 μg/kg/min) caused a similar change in systolic circumferential strain rate as was found during 48 h of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic–systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease. Key points Preclinical evidence strongly suggests that myocardial lipid accumulation (termed steatosis) is an important mechanism driving heart disease. Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities. Using a 48‐h food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction. These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target.