scholarly journals Reactive hyperemia: a review of methods, mechanisms, and considerations

2020 ◽  
Vol 318 (3) ◽  
pp. R605-R618 ◽  
Author(s):  
Ryan Rosenberry ◽  
Michael D. Nelson

Reactive hyperemia is a well-established technique for noninvasive assessment of peripheral microvascular function and a predictor of all-cause and cardiovascular morbidity and mortality. In its simplest form, reactive hyperemia represents the magnitude of limb reperfusion following a brief period of ischemia induced by arterial occlusion. Over the past two decades, investigators have employed a variety of methods, including brachial artery velocity by Doppler ultrasound, tissue reperfusion by near-infrared spectroscopy, limb distension by venous occlusion plethysmography, and peripheral artery tonometry, to measure reactive hyperemia. Regardless of the technique used to measure reactive hyperemia, blunted reactive hyperemia is believed to reflect impaired microvascular function. With the advent of several technological advancements, together with an increased interest in the microcirculation, reactive hyperemia is becoming more common as a research tool and is widely used across multiple disciplines. With this in mind, we sought to review the various methodologies commonly used to assess reactive hyperemia and current mechanistic pathways believed to contribute to reactive hyperemia and reflect on several methodological considerations.

1996 ◽  
Vol 81 (3) ◽  
pp. 1418-1422 ◽  
Author(s):  
D. N. Proctor ◽  
J. R. Halliwill ◽  
P. H. Shen ◽  
N. E. Vlahakis ◽  
M. J. Joyner

Estimates of calf blood flow with venous occlusion plethysmography vary widely between studies, perhaps due to the use of different plethysmographs. Consequently, we compared calf blood flow estimates at rest and during reactive hyperemia in eight healthy subjects (four men and four women) with two commonly used plethysmographs: the mercury-in-silastic (Whitney) strain gauge and Dohn air-filled cuff. To minimize technical variability, flow estimates were compared with a Whitney gauge and a Dohn cuff on opposite calves before and after 10 min of bilateral femoral arterial occlusion. To account for any differences between limbs, a second trial was conducted in which the plethysmographs were switched. Resting flows did not differ between the plethysmographs (P = 0.096), but a trend toward lower values with the Whitney was apparent. Peak flows averaged 37% lower with the Whitney (27.8 +/- 2.8 ml.dl-1.min-1) than with the Dohn plethysmograph (44.4 +/- 2.8 ml.dl-1.min-1; P < 0.05). Peak flow expressed as a multiple above baseline was also lower with the Whitney (10-fold) than with the Dohn plethysmograph (14.5-fold; P = 0.02). Across all flows at rest and during reactive hyperemia, estimates were highly correlated between the plethysmographs in all subjects (r2 = 0.96-0.99). However, the mean slope for the Whitney-Dohn relationship was only 60 +/- 2%, indicating that over a wide range of flows the Whitney gauge estimate was 40% lower than that for the Dohn cuff. These results demonstrate that the same qualitative results can be obtained with either plethysmograph but that absolute flow values will generally be lower with Whitney gauges.


2020 ◽  
pp. 1-19
Author(s):  
Marieta P. Theodorakopoulou ◽  
Maria Schoina ◽  
Pantelis Sarafidis

<b><i>Background:</i></b> Endothelium is the inner cellular lining of the vessels that modulates multiple biological processes including vasomotor tone, permeability, inflammatory responses, hemostasis, and angiogenesis. Endothelial dysfunction, the basis of atherosclerosis, is characterized by an imbalance between endothelium-derived relaxing factors and endothelium-derived contracting factors. <b><i>Summary:</i></b> Starting from the semi-invasive venous occlusion plethysmography, several functional techniques have been developed to evaluate microvascular function and subsequently used in patients with CKD. Flow-mediated dilatation of the forearm is considered to be the “gold standard,” while in the last years, novel, noninvasive methods such as laser speckle contrast imaging and near-infrared spectroscopy are scarcely used. Moreover, several circulating biomarkers of endothelial function have been used in studies in CKD patients. This review summarizes available functional methods and biochemical markers for the assessment of endothelial and microvascular function in CKD and discusses existing evidence on their associations with comorbid conditions and outcomes in this population. <b><i>Key Messages:</i></b> Accumulated evidence suggests that endothelial dysfunction occurs early in CKD and is associated with target organ damage, progression of renal injury, cardiovascular events, and mortality. Novel methods evaluating microvascular function can offer a detailed, real-time assessment of underlying phenomena and should be increasingly used to shed more light on the role of endothelial dysfunction on cardiovascular and renal disease progression in CKD.


1965 ◽  
Vol 209 (6) ◽  
pp. 1106-1114 ◽  
Author(s):  
Hermes A. Kontos ◽  
H. Page Mauck ◽  
John L. Patterson

Reactive hyperemia was studied in the hindlimb and forelimb of 81 anesthetized dogs. Reactive hyperemia volume in response to 5-sec arterial occlusions correlated moderately well with the decrease in intravascular pressure. This correlation was poor for 30-sec arterial occlusions. Venous congestion induced by venous occlusion decreased or abolished the vasodilator response to 5-sec arterial occlusions and decreased the response to 30-sec occlusions. Evidence is presented supporting the view that this effect of venous congestion was related to reduction in the fall in intravascular pressure during arterial occlusion. The response to 30-sec occlusions was decreased during acutely induced hypocapnia and increased following acetazolamide administration. The data support the view that both physical and metabolic factors contribute to the production of reactive hyperemia. They further suggest that the accumulation of CO2 in the ischemic tissues contributes to the production of reactive hyperemia.


1980 ◽  
Vol 238 (6) ◽  
pp. G478-G484
Author(s):  
P. R. Kvietys ◽  
T. Miller ◽  
D. N. Granger

In a denervated autoperfused dog colon preparation, arterial perfusion pressure, venous outflow pressure, blood flow, and arteriovenous O2 difference were measured during graded arterial pressure alterations, arterial occlusion, venous pressure elevation, venous occlusion, and local intra-arterial infusion of adenosine. As perfusion pressure was reduced from 100 to 30 mmHg, colonic blood flow decreased and arteriovenous O2 difference increased. Although blood flow was not autoregulated O2 delivery was maintained within 10% of control between 70 to 100 mmHg and then decreased with further reduction in perfusion pressure. Arterial occlusion (15, 30, and 60 s) resulted in a postocclusion reactive hyperemia; the magnitude of the hyperemia was directly related to the duration of occlusion. Venous occlusion resulted in a postocclusion reactive hypoemia. Elevation of venous pressure from 0 to 20 mmHg increased vascular resistance, O2 extraction, and the capillary filtration coefficient, but decreased O2 delivery. Infusion of adenosine decreased vascular resistance and O2 extraction, but increased O2 delivery. These data suggest that both metabolic and myogenic mechanisms are involved in the control of colonic blood flow and oxygenation.


2019 ◽  
Vol 317 (4) ◽  
pp. R530-R538 ◽  
Author(s):  
Ryan Rosenberry ◽  
Darian Trojacek ◽  
Susie Chung ◽  
Daisha J. Cipher ◽  
Michael D. Nelson

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.


2001 ◽  
Vol 90 (2) ◽  
pp. 511-519 ◽  
Author(s):  
Mireille C. P. Van Beekvelt ◽  
Willy N. J. M. Colier ◽  
Ron A. Wevers ◽  
Baziel G. M. Van Engelen

The aim of this study was to investigate local muscle O2consumption (muscV˙o 2) and forearm blood flow (FBF) in resting and exercising muscle by use of near-infrared spectroscopy (NIRS) and to compare the results with the global muscV˙o 2 and FBF derived from the well-established Fick method and plethysmography. muscV˙o 2 was derived from 1) NIRS using venous occlusion, 2) NIRS using arterial occlusion, and 3) the Fick method [muscV˙o 2 (Fick)]. FBF was derived from 1) NIRS and 2) strain-gauge plethysmography. Twenty-six healthy subjects were tested at rest and during sustained isometric handgrip exercise. Local variations were investigated with two independent and simultaneously operating NIRS systems at two different muscles and two measurement depths. muscV˙o 2 increased more than fivefold in the active flexor digitorum superficialis muscle, and it increased 1.6 times in the brachioradialis muscle. The average increase in muscV˙o 2 (Fick) was twofold. FBF increased 1.4 times independent of the muscle or the method. It is concluded that NIRS is an appropriate tool to provide information about local muscV˙o 2 and local FBF because both place and depth of the NIRS measurements reveal local differences that are not detectable by the more established, but also more global, Fick method.


2021 ◽  
Vol 20 ◽  
Author(s):  
Gustavo Vieira de Oliveira ◽  
Mônica Volino-Souza ◽  
Renata Leitão ◽  
Vivian Pinheiro ◽  
Carlos Adam Conte-Júnior ◽  
...  

Abstract Background There is a spectrum of possibilities for analyzing muscle O2 resaturation parameters for measurement of reactive hyperemia in microvasculature. However, there is no consensus with respect to the responsiveness of these O2 resaturation parameters for assessing reactive hyperemia. Objectives This study investigates the responsiveness of the most utilized muscle O2 resaturation parameters to assess reactive hyperemia in the microvasculature of a clinical group known to exhibit impairments of tissue O2 saturation (StO2). Methods Twenty-three healthy young adults, twenty-nine healthy older adults, and thirty-five older adults at risk of cardiovascular disease (CVD) were recruited. Near-infrared spectroscopy (NIRS) was used to assess StO2 after a 5-min arterial occlusion challenge and the following parameters were analyzed: StO2slope_10s, StO2slope_30s, and StO2slope_until_baseline (upslope of StO2 over 10s and 30s and until StO2 reaches the baseline value); time to StO2baseline and time to StO2max (time taken for StO2 to reach baseline and peak values, respectively); ∆StO2reperfusion (the difference between minimum and maximum StO2 values); total area under the curve (StO2AUCt); and AUC above the baseline value (StO2AUC_above_base). Results Only StO2slope_10s was significantly slower in older adults at risk for CVD compared to healthy young individuals (p < 0.001) and to healthy older adults (p < 0.001). Conversely, time to StO2max was significantly longer in healthy young individuals than in older adult at CVD risk. Conclusions Our findings suggest that StO2slope_10s may be a measure of reactive hyperemia, which provides clinical insight into microvascular function assessment.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Schoina ◽  
Charalampos Loutradis ◽  
Evangelos Memmos ◽  
Eva Triantafillidou ◽  
Eleni Pagkopoulou ◽  
...  

Abstract Background and Aims Αlterations in endothelial function and capillary circulation have been associated with increased cardiovascular events and overall mortality. Both diabetes mellitus (DM) and chronic kidney disease (CKD) have been associated with microcirculatory damage. Nailfold video-capillaroscory can provide a thorough assessment of capillary density and microcirculation changes. This is the first study examining in comparison microcirculatory function parameters in diabetic and non-diabetic patients with CKD. Method We included 48 diabetic and 48 non-diabetic adult patients (&gt;18 years) with CKD (eGFR: &lt;90 and ≥15mL/min/1.73m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase). Results Baseline demographic, anthropometric and laboratory characteristics were similar between patients with and without diabetes in total and in CKD stages. Overall, no significant differences at baseline capillary density were observed between groups; however diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3±3.8 vs 38.3±4.3 capillaries/mm2, p=0.022) and at venous congestion (37.8±4.0 vs 39.8±4.2 capillaries/mm2, p=0.015). When stratified according to CKD stages, the between-group differences in parameters of interest were not significant in stages 2, 3a and 4. In stage 3b, capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline (31.1±2.8 vs 33.4±3.4 capillaries/mm2, p=0.044), during postocclusive hyperemia (36.8±2.7 vs 40.0±4.3 capillaries/mm2, p=0.037) and venous congestion (38.3±2.8 vs 41.5±3.5 capillaries/mm2, p=0.022). Conclusion Capillary density during postocclusive reactive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory functional impairment in CKD. These differences are more prominent in CKD stage 3b, and less prominent in earlier and later stages.


1961 ◽  
Vol 16 (5) ◽  
pp. 851-857 ◽  
Author(s):  
David I. Abramson ◽  
Samuel Tuck ◽  
Yvonne Bell ◽  
Roscoe E. Mitchell ◽  
Agenor M. Zayas

In 17 experiments, performed on the forearm of normal subjects, the effect of 2½, 5, and 10 min of arterial occlusion was studied. Blood flow was obtained with the venous occlusion plethysmograph, and oxygen uptake was calculated using the Fick principle. Arterial occlusion resulted in the production of an oxygen debt which was subsequently repaid. With progressively longer periods of anoxia there was a proportionate increase in the magnitude of the debt. Similar conclusions could not be drawn from blood flow studies alone, since the vascular change represented only one means of repayment of the oxygen debt during reactive hyperemia, the other being a greater extraction of oxygen from each unit of blood early in the postocclusion period. The constant overswing on either side of the control base line, observed in the records of oxygen uptake, suggested the absence of delicately balanced and efficient checks on the mechanisms responsible for repayment of the oxygen debt incurred in the period of tissue anoxia. Submitted on March 27, 1961


2019 ◽  
Vol 317 (5) ◽  
pp. R746-R753
Author(s):  
Elizabeth C. Schroeder ◽  
Thessa I. M. Hilgenkamp ◽  
Wesley K. Lefferts ◽  
Nadia Robinson ◽  
Tracy Baynard ◽  
...  

Acute inflammation is associated with increased risk of cardiovascular events and impaired vasodilatory capacity. Vasodilatory capacity can be measured in different segments of the arterial tree; however, it is unknown if the effects of acute inflammation are vascular segment-specific or if inflammation-induced dysfunction can be attenuated by factors that modulate cardiovascular risk, such as high cardiorespiratory fitness. The purpose of this study was to determine the effect of acute inflammation and fitness on conduit artery, resistance artery, and microvascular function in healthy, young adults. Vascular function was assessed at baseline and 24 h after a typhoid vaccination in 11 low-fit (5 male, 24 yr of age, 34.5 ± 2.9 ml·kg−1·min−1 peak O2 uptake (V̇o2peak)] and 12 high-fit (7 male, 27 yr of age, 56.4 ± 9.7 ml·kg−1·min−1 V̇o2peak) young adults. Vascular assessments included flow-mediated dilation (FMD) of the brachial artery, forearm reactive hyperemia (RH) via venous occlusion plethysmography, and near-infrared spectroscopy (NIRS) during a 5-min arterial occlusion. Acute inflammation was evident with increases in IL-6 and C-reactive protein ( P < 0.01), and mean arterial pressure did not change ( P = 0.33). FMD was lower in the high-fit group, yet it was reduced in both groups at 24 h, even after controlling for shear ( P < 0.05). No effect of acute inflammation was observed for RH or NIRS ( P > 0.05). Acute inflammation had nonuniform effects on vascular function throughout the arterial tree in young adults, and fitness did not alter the vascular response. This suggests that cardiorespiratory fitness may not protect the vasculature during acute inflammation in young adults in the absence of age- or disease-related decline in vascular function.


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