Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure

Endothelial cell dysfunction (ECD) has been demonstrated in patients with end-stage renal disease (ESRD) who have cardiovascular disease (CD) or diabetes mellitus (DM). While techniques to examine conduit arteries have been adapted to these patients, evaluation of microvascular function has lagged behind. Therefore, we used laser Doppler flowmetry (LDF) and scanned laser Doppler imaging (LDI) to quantify parameters of the postocclusion reactive hyperemia and thermal hyperemic responses (local heating to 43°C) in ESRD patients ( n = 63) and healthy individuals ( n = 33). Patients with ESRD were partitioned among those with either CD or DM or both (designated CDorDM, n = 30), patients with both CD and DM (designated CD+DM, n = 12, statistically similar to CDorDM), and patients with neither CD or DM (designated ∼CDorDM, n = 33). LDF during thermal hyperemia showed a decrease in the thermal peaks and plateau as well as a delay in plateau compared with control, consistent with ECD. LDF during reactive hyperemia showed a decrease in the pay-back area under the curve, also consistent with ECD. ∼CDorDM were heterogeneous: almost 50% contained flow abnormalities similar to CDorDM. There was also a reduction in the number of functional arterioles on LDI images. Fourier analysis of LDF oscillations showed that low-frequency oscillations characterizing endothelial function were impaired in CDorDM and in many ∼CDorDM. The data demonstrate that ESRD patients with expected ECD (CDorDM) are characterized by distinct abnormalities in LDF parameters. However, similar abnormalities are found in approximately one-half of ESRD patients without evidence for CD or DM. Postocclusive and thermal interrogation of the microvasculature with laser Doppler-resolved parameters of the microcirculation, followed by Fourier analysis of the very slow oscillations, may provide a valuable adjunct to early noninvasive diagnosis of ECD in ESRD, especially important in a subpopulation of ESRD patients with no known CD or DM, which could be at increased risk of impending clinical manifestations of vasculopathy.

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Limb perfusion in the lower limb amputee—a comparative study using a laser Doppler flowmeter and a transcutaneous oxygen electrode

Prosthetics and Orthotics International ◽

10.3109/03093648709078183 ◽

1987 ◽

Vol 11 (2) ◽

pp. 80-84 ◽

Cited By ~ 13

Author(s):

S. L. E. Fairs ◽

R. O. Ham ◽

B. A. Conway ◽

V. C. Roberts

Keyword(s):

Laser Doppler Flowmetry ◽

Lower Limb ◽

Local Heating ◽

Objective Assessment ◽

Relative Increase ◽

Laser Doppler ◽

Transcutaneous Oxygen ◽

Doppler Flowmetry ◽

Amputation Level ◽

Significant Difference

Accurate and objective assessment of amputation level in the lower limb plays an important role in patient management. Laser Doppler flowmetry (LDF) is a new and noninvasive technique for skin blood flow measurement and has been used pre-operatively in 25 patients undergoing amputation for vascular disease and in five normal controls. Baseline flux measurements were made at room temperature on the medial aspect of legs and then again after local heating of the skin for five minutes. Transcutaneous oxygen measurements were made at the same site for comparison and amputation level in patients selected on this basis. Significant differences (p<0.001) in TcPO2 values were found between controls (10.9±0.5kPa), below-knee (BK) amputees (6.0±1.5kPa) and above-knee (AK) amputees (1.5±0.6kPa). Baseline LDF flux did not differ significantly between any group. Heated flux values did however show a significant difference (p<0.005) between controls (52.4±23.5) and both BK (20.6±9.2) and AK groups (8.1±7.7) and also between the amputee groups. The relative increase in flux (heated flux/baseline flux) differed significantly between the BK (3.3±1.5) and AK (1.2±0.3) groups (p<0.001) and between these two and the controls (11.2±5.4) (p<0.001). The correlation between relative increase in flux and TcPO2 was 0.7 (p<0.001). It is concluded that laser Doppler flowmetry used in conjunction with thermal stressing could provide a quick, simple and non-invasive method for objectively determining amputation level in the lower limb.

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Skin Reactive Hyperemia in Diabetic Patients: A Study by Laser Doppler Flowmetry

Diabetes Care ◽

10.2337/diacare.14.11.958 ◽

1991 ◽

Vol 14 (11) ◽

pp. 958-962 ◽

Cited By ~ 45

Author(s):

E. Tur ◽

G. Yosipovitch ◽

Y. Bar-On

Keyword(s):

Laser Doppler Flowmetry ◽

Reactive Hyperemia ◽

Laser Doppler ◽

Diabetic Patients ◽

Doppler Flowmetry

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The acute impact of local cooling versus local heating on human skin microcirculation using laser Doppler flowmetry and tissue spectrophotometry

Burns ◽

10.1016/j.burns.2019.03.009 ◽

2020 ◽

Vol 46 (1) ◽

pp. 104-109 ◽

Cited By ~ 2

Author(s):

Dominik Bender ◽

Stephanie Tweer ◽

Frank Werdin ◽

Jens Rothenberger ◽

Adrien Daigeler ◽

...

Keyword(s):

Human Skin ◽

Laser Doppler Flowmetry ◽

Local Heating ◽

Laser Doppler ◽

Local Cooling ◽

Skin Microcirculation ◽

Doppler Flowmetry

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Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01217.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. H425-H432 ◽

Cited By ~ 48

Author(s):

Marvin S. Medow ◽

Indu Taneja ◽

Julian M. Stewart

Keyword(s):

Nitric Oxide ◽

Peak Flow ◽

Reactive Hyperemia ◽

Laser Doppler ◽

Doppler Flowmetry ◽

Time To Peak ◽

Flow Parameters ◽

Cox Inhibitor ◽

Cutaneous Circulation ◽

Synthase Inhibitor

We tested the hypothesis that cyclooxygenases (COXs) or COX products inhibit nitric oxide (NO) synthesis and thereby mask potential effects of NO on reactive hyperemia in the cutaneous circulation. We performed laser-Doppler flowmetry (LDF) with intradermal microdialysis in 12 healthy volunteers aged 19–25 yr. LDF was expressed as the percent cutaneous vascular conduction (%CVC) or as the maximum %CVC (%CVCmax) where CVC is LDF/mean arterial pressure. We tested the effects of the nonisoform-specific NO synthase inhibitor nitro-l-arginine (NLA, 10 mM), the nonspecific COX inhibitor ketorolac (Keto, 10 mM), combined NLA + Keto, and NLA + sodium nitroprusside (SNP, 28 mM) on baseline and reactive hyperemia flow parameters. We also examined the effects of isoproterenol, a β-adrenergic agonist that causes prostaglandin-independent vasodilation to correct for the increase in baseline flow caused by Keto. When delivered directly into the intradermal space, Keto greatly augments all aspects of the laser-Doppler flow response to reactive hyperemia: peak reactive hyperemic flow increased from 41 ± 5 to 77 ± 7%CVCmax, time to peak flow increased from 17 ± 3 to 56 ± 24 s, the area under the reactive hyperemic curve increased from 1,417 ± 326 to 3,376 ± 876%CVCmax·s, and the time constant for the decay of peak flow increased from 100 ± 23 to 821 ± 311 s. NLA greatly attenuates the Keto response despite exerting no effects on baseline LDF or on reactive hyperemia when given alone. Low-dose NLA + SNP duplicates the Keto response. Isoproterenol increased baseline and peak reactive flow. These results suggest that COX inhibition unmasks NO dependence of reactive hyperemia in human cutaneous circulation.

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S-Transform Applied to Laser Doppler Flowmetry Reactive Hyperemia Signals

IEEE Transactions on Biomedical Engineering ◽

10.1109/tbme.2005.863843 ◽

2006 ◽

Vol 53 (6) ◽

pp. 1032-1037 ◽

Cited By ~ 50

Author(s):

S. Assous ◽

A. Humeau ◽

M. Tartas ◽

P. Abraham ◽

J.P. L'Huillier

Keyword(s):

Laser Doppler Flowmetry ◽

Reactive Hyperemia ◽

Laser Doppler ◽

Doppler Flowmetry ◽

S Transform

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Laser Doppler flowmetry: multifractal spectra of signals recorded in hand of young healthy subjects before and after local heating

IFMBE Proceedings - World Congress on Medical Physics and Biomedical Engineering, September 7 - 12, 2009, Munich, Germany ◽

10.1007/978-3-642-03882-2_516 ◽

2009 ◽

pp. 1944-1947

Author(s):

B. Buard ◽

G. Mahé ◽

F. Chapeau-Blondeau ◽

D. Rousseau ◽

P. Abraham ◽

...

Keyword(s):

Laser Doppler Flowmetry ◽

Healthy Subjects ◽

Local Heating ◽

Laser Doppler ◽

Doppler Flowmetry ◽

Multifractal Spectra ◽

Before And After

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The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology

Folia Medica ◽

10.1515/folmed-2016-0011 ◽

2016 ◽

Vol 58 (2) ◽

pp. 77-88 ◽

Cited By ~ 2

Author(s):

Sevdalina N. Lambova

Keyword(s):

Differential Diagnosis ◽

Systemic Sclerosis ◽

Doppler Ultrasound ◽

Predictive Value ◽

Laser Doppler ◽

Nailfold Capillaroscopy ◽

Doppler Imaging ◽

Peripheral Arteries ◽

Doppler Flowmetry ◽

Instrumental Methods

AbstractMicro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud’s phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome.The current review discusses the instrumental methods for vascular assessments.Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

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Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00366.2012 ◽

2013 ◽

Vol 305 (4) ◽

pp. R452-R458 ◽

Cited By ~ 10

Author(s):

Jessica D. Dahmus ◽

Rebecca S. Bruning ◽

W. Larry Kenney ◽

Lacy M. Alexander

Keyword(s):

Local Heating ◽

Reactive Hyperemia ◽

Area Under The Curve ◽

Control Site ◽

Microvascular Function ◽

Sensory Nerves ◽

Controlled Study ◽

Double Blind ◽

Doppler Flowmetry ◽

Cutaneous Vasodilation

Platelet P2Y12-ADP and COX-1 receptor inhibition with oral clopidogrel (CLO) and low-dose aspirin (ASA), respectively, attenuates reflex-mediated cutaneous vasodilation, but little is known about how these medications affect local vasodilatory signaling. Reactive hyperemia (RH) results in vasodilation that is mediated by sensory nerves and endothelium-derived hyperpolarization factors (EDHF) through large-conductance calcium-activated potassium channels, whereas slow local heating (LH) elicits vasodilation largely through the production of nitric oxide (NO). We hypothesized that CLO and ASA would attenuate locally mediated cutaneous vasodilation assessed by RH and LH (0.5°C/min). In a randomized, cross-over, double-blind placebo-controlled study, nine healthy men and women (56 ± 1 yr) took CLO (75 mg), ASA (81 mg), and placebo for 7 days. Skin blood flow was measured (laser-Doppler flowmetry, LDF) and cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal CVC (%CVCmax: 43°C and 28 mM sodium nitroprusside). RH response parameters, including area under the curve (AUC), total hyperemic response (THR), and the decay constant tau (λ) were calculated. NO-dependent vasodilation during LH was assessed by calculating the difference in %CVCmax between a control site and an NO synthase-inhibited site (10 mM l-NAME: intradermal microdialysis). CLO augmented the AUC and THR (AUCclo = 3,783 ± 342; THRclo = 2,306 ± 266% CVCmax/s) of the RH response compared with ASA (AUCASA = 3,101 ± 325; THRASA = 1,695 ± 197% CVCmax/s) and placebo (AUCPlacebo = 3,000 ± 283; THRPlacebo = 1,675 ± 170% CVCmax/s; all P < 0.0001 vs. CLO). There was no difference in the LH response or calculated NO-dependent vasodilation among treatments (all P > 0.05). Oral CLO treatment augments vasodilation during RH but not LH, suggesting that CLO may improve cutaneous microvascular function.

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The role of baseline in the cutaneous vasoconstrictor responses during combined local and whole body cooling in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00815.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. H3187-H3192 ◽

Cited By ~ 29

Author(s):

Gary J. Hodges ◽

Wojciech A. Kosiba ◽

Kun Zhao ◽

Guy E. Alvarez ◽

John M. Johnson

Keyword(s):

Blood Flow ◽

Skin Blood Flow ◽

Local Heating ◽

Laser Doppler ◽

Whole Body ◽

Local Cooling ◽

Doppler Flowmetry ◽

Vasoconstrictor Response ◽

Body Cooling ◽

Whole Body Cooling

Previous work showed that local cooling (LC) attenuates the vasoconstrictor response to whole body cooling (WBC). We tested the extent to which this attenuation was due to the decreased baseline skin blood flow following LC. In eight subjects, skin blood flow was assessed using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was expressed as LDF divided by blood pressure. Subjects were dressed in water-perfused suits to control WBC. Four forearm sites were prepared with microdialysis fibers, local heating/cooling probe holders, and laser-Doppler probes. Three sites were locally cooled from 34 to 28°C, reducing CVC to 45.9 ± 3.9, 42 ± 3.9, and 44.5 ± 4.8% of baseline ( P < 0.05 vs. baseline; P > 0.05 among sites). At two sites, CVC was restored to precooling baseline levels with sodium nitroprusside (SNP) or isoproterenol (Iso), increasing CVC to 106.4 ± 12.4 and 98.9 ± 10.1% of baseline, respectively ( P > 0.05 vs. precooling). Whole body skin temperature, apart from the area of blood flow measurement, was reduced from 34 to 31°C. Relative to the original baseline, CVC decreased ( P < 0.05) by 44.9 ± 2.8 (control), 11.3 ± 2.4 (LC only), 29 ± 3.7 (SNP), and 45.8 ± 8.7% (Iso). The reductions at LC only and SNP sites were less than at control or Iso sites ( P < 0.05); the responses at those latter sites were not different ( P > 0.05), suggesting that the baseline change in CVC with LC is important in the attenuation of reflex vasoconstrictor responses to WBC.

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