Interindividual differences in the ischemic stimulus and other technical considerations when assessing reactive hyperemia

Abstract

Reactive hyperemia is an established, noninvasive technique to assess microvascular function and a powerful predictor of all-cause and cardiovascular morbidity and mortality. Emerging evidence from our laboratory suggests a close link between reactive hyperemia and the metabolic rate of the ischemic limb and the existence of large interindividual differences contributing to markedly different stimuli to vasodilate. Here we relate forearm tissue desaturation (i.e., the ischemic stimulus to vasodilate, measured by near-infrared spectroscopy) to brachial artery hyperemic velocity and flow (measured using duplex ultrasound) across a wide range of ischemic stimuli. Twelve young and 11 elderly individuals were prospectively studied. To recapitulate conventional vascular occlusion testing, reactive hyperemia was first assessed using a standard 5-min occlusion period. Then, to evaluate the dose dependence of tissue ischemia on reactive hyperemia, we randomly performed 4-, 6-, and 8-min cuff occlusions in both groups. In all cases, peak velocity, as well as the 5-s average velocity, immediately after the cuff occlusion was significantly higher in the young than the elderly group; however, tissue desaturation was also much more pronounced in the young group ( P < 0.05), representing a greater ischemic stimulus. Remarkably, when reactive hyperemia was adjusted for the ischemic vasodilatory stimulus, group differences in reactive hyperemia were abrogated. Together, these data challenge conventional interpretations of reactive hyperemia and show that the ischemic stimulus to vasodilate varies across individuals and that the level of reactive hyperemia is often coupled to the magnitude of tissue desaturation.

Influence of cuff‐occlusion duration on contrast‐enhanced ultrasound assessments of calf muscle microvascular blood flow responsiveness in older adults

“…The inclusion of a broad age range and not accounting for physical activity or fitness levels may have also contributed to variance in our data (Black, Green, & Cable, 2008); however, this may also strengthen the generalizability of our findings. Furthermore, the direct relationship between occlusion duration and the magnitude of post-occlusion CEUS measurements in the current study is consistent with findings from other hyperaemic response studies using plethysmography (Bauer, Bruegger, Gamble, & Christ, 2002) and NIRS (Iannetta et al, 2019;McLay et al, 2016;Rosenberry et al, 2018;Rosenberry, Trojacek, Chung, Cipher, & Nelson, 2019).…”

Suitability of the muscle O2 resaturation parameters most used for assessing reactive hyperemia: a near-infrared spectroscopy study

“… 13 , 18 Our findings demonstrated that only StO 2slope _ 10s was significantly slower in older adults with CVD risk factors compared to healthy older adults and to healthy young individuals, suggesting that StO 2slope_10s may be a more sensitive NIRS parameter for assessing reactive hyperemia. The StO 2slope _ 10s has typically been adopted to assess O 2 resaturation rate, since previous studies have reported that this parameter is correlated with reactive hyperemia measured in the brachial artery 20 and with FMD response. 8 , 11 It has been postulated that the StO 2slope _ 10s may be a stimulus for FMD response given that FMD is evoked by increasing blood flow after cuff release.…”

“…The inclusion criteria for older adults at high risk for CVD were age ≥ 60 years and possessing at least four CVD risk factors, according to a previous study demonstrating that presence of three or more CVD risk factors is related to microvascular dysfunction. 10 , 20 The following CVD risk factors were used as inclusion criteria: triglycerides ≥ 150 mg/dL; total-cholesterol ≥ 200 mg/dL; LDL-cholesterol ≥ 150 mg/dL, HDL-cholesterol ≤ 40 mg/dL for men and ≤ 50 mg/dL for women; high-blood glucose ≥ 120 mg/dL and/or taking oral hypoglycemic medications; and high systolic blood pressure (SBP) ≥ 135 mm Hg, and/or high diastolic blood pressure (DBP) ≥ 90 mm Hg, and/or taking anti-hypertensive medications. The exclusion criteria included human immunodeficiency virus (HIV); cancer; rheumatoid arthritis; smoking; and chronic obstructive pulmonary disease; as well as participants not being engaged in any exercise program.…”

Shear stress‐induced flow‐mediated dilatation: is it up to haemoglobin?

“…While reduced NO scavenging by haemoglobin is a very plausible explanation, as put forth by the investigators, it is interesting to consider the role of reduced arterial oxygen content (and oxygen delivery) on the present results. Indeed, our laboratory has recently highlighted the importance of the 'ischaemic stimulus' on reactive hyperaemia (Rosenberry et al 2019). While the between condition difference in peak reactive hyperaemia did not reach statistical significance, there was a clear trend favouring the Journal Club J Physiol 598.24 haemodilution condition.…”

“…Indeed, our laboratory has recently highlighted the importance of the ‘ischaemic stimulus’ on reactive hyperaemia (Rosenberry et al . 2019). While the between condition difference in peak reactive hyperaemia did not reach statistical significance, there was a clear trend favouring the haemodilution condition.…”