Laser Doppler Flux Research Articles

Effect of sub‐occipital release on steady‐state and dynamic oscillatory features of the cardiovascular system (1170.7)

To determine if sub‐occipital release (SOR) modulates sympathetic control during basal conditions and in conditions with acutely increased activity, 9 healthy subjects (5 male, 4 female) participated in 2 protocols: 1) cold stress (15°C water perfused through a high‐density tube‐lined suit for 20 min) to increase sympathetic tone and 2) normothermia (34°C). In each thermal condition, subjects received in random order, SOR and yaw sham (30 cycles/min) for 2 min. Measurements included: heart rate (HR; ECG); mean arterial blood pressure (MAP; photoplethysmography); cutaneous vascular conductance (CVC; laser‐Doppler flux/MAP); stroke volume (SV; Modelflow); systemic vascular resistance (SVR; Modelflow); and low frequency (LF; 0.04‐0.15 Hz) spectral power (Fast‐Fourier Transform). Cold stress increased MAP (SOR: 90±2 to 98±2; yaw: 87±2 to 99±2 mmHg) and SVR (SOR: 15±2 to 17±2; yaw: 15±2 to 17±2 units), decreased CVC (SOR: 0.52±0.22 to 0.26±0.14; yaw: 0.46±0.15 to 0.24±0.11 units, normothermia to cold stress, respectively), and did not significantly change HR or SV. Blood pressure and laser‐Doppler flux LF spectral power also increased during cold stress. No significant differences were observed between SOR and yaw during normothermia or cold stress. These data indicate that cold stress increases sympathetic noradrenergic tone but SOR does not have the capability to modulate these variables.Grant Funding Source: Supported by a grant from the American Osteopathic Association

Tempol improves cutaneous thermal hyperemia through increasing nitric oxide bioavailability in young smokers

We recently found that young cigarette smokers display cutaneous vascular dysfunction relative to nonsmokers, which is partially due to reduced nitric oxide (NO) synthase (NOS)-dependent vasodilation. In this study, we tested the hypothesis that reducing oxidative stress improves NO bioavailability, enhancing cutaneous vascular function in young smokers. Ten healthy young male smokers, who had smoked for 6.3 ± 0.7 yr with an average daily consumption of 9.1 ± 0.7 cigarettes, were tested. Cutaneous vascular conductance (CVC) during local heating to 42°C at a rate of 0.1°C/s was evaluated as laser-Doppler flux divided by mean arterial blood pressure and normalized to maximal CVC, induced by local heating to 44°C plus sodium nitroprusside administration. We evaluated plateau CVC during local heating, which is known to be highly dependent on NO, at four intradermal microdialysis sites with 1) Ringer solution (control); 2) 10 μM 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol), a superoxide dismutase mimetic; 3) 10 mM N(ω)-nitro-l-arginine (l-NNA), a nonspecific NOS inhibitor; and 4) a combination of 10 μM tempol and 10 mM l-NNA. Tempol increased plateau CVC compared with the Ringer solution site (90.0 ± 2.3 vs. 77.6 ± 3.9%maximum, P = 0.028). Plateau CVC at the combination site (56.8 ± 4.5%maximum) was lower than the Ringer solution site (P < 0.001) and was not different from the l-NNA site (55.1 ± 4.6%maximum, P = 0.978), indicating the tempol effect was exclusively NO dependent. These data suggest that in young smokers, reducing oxidative stress improves cutaneous thermal hyperemia to local heating by enhancing NO production.

Capsaicin 8% patch for treprostinil subcutaneous infusion site pain in pulmonary hypertension patients

BackgroundTreprostinil sodium improves haemodynamics and symptoms in pulmonary arterial hypertension (PAH) patients, but its subcutaneous (s.c.) administration can produce severe local site pain, and lead to discontinuation of vital treatment. Treprostinil is a prostacyclin analogue which stimulates prostacyclin receptors in skin nociceptor terminals, resulting in pain and cutaneous hypersensitivity, for which current pain remedies have limited effect. Capsaicin 8% patch relieves neuropathic pain for 3 months after a single 60 min cutaneous application; we investigated whether its pre-application can reduce s.c. trepostinil-induced pain. MethodsA single-centre, double-blind, randomized, placebo-controlled, crossover study was conducted to assess the safety and efficacy of a single capsaicin 8% patch pre-application for s.c. treprostinil pain in 11 PAH patients, relative to control patch with low-dose capsaicin 0.075% cream. ResultsThe primary efficacy endpoint, mean difference between the two treatment arms in an 11-point numerical pain rating scale from baseline to 2 weeks after patch applications, was significantly lower on the capsaicin 8% patch treatment arm [P=0.01, mean difference=−1.47 units, 95% credible interval (CI): −2. 59 to −0.38] in the patients who completed the study per protocol, although intention-to-treat analysis did not show significant difference (P=0.28). Heat pain thresholds were decreased (P=0.027, mean difference=5.43°C, 95% CI: 0.71–10.21) and laser Doppler flux increased (P=0.016, mean difference=370 units, 95% CI: 612 to 127.9) at the application site immediately after capsaicin 8% patch, confirming activity. ConclusionsFurther investigation of the efficacy of capsaicin 8% patch in this indication is warranted. Clinical trial registrationClinicalTrials.gov: NCT01393795.

The effect of L-arginine on microvascular reactivity in normotensive subjects with a family history of hypertension

Background : An increasing number of studies support the hypothesis that endothelial dysfunction due to reduced availability of nitric oxide plays a key role in initiation, development and progression of essential hypertension. The aim of our study was to determine whether the ingestion of L-arginine actually improves microvascular function in normotensive subjects with a family history of hypertension. Methods : 30 normotensive healthy men, aged 20–30 years, were divided into two groups according to the family history of hypertension. We measured ECG, heart rate, systolic and diastolic arterial pressure, cardiac output, stroke volume, total peripheral resistance (Task Force Monitor) and laser Doppler (LD) flux in the microvessels of the skin on the forearm at rest, before and after the administration of 0.9 g L-arginine. The endothelium-dependent vasodilation was assessed by iontophoresis of acetylcholine and the endothelium-independent vasodilation by iontophoresis of sodium nitroprusside. Results : After the ingestion of L-arginine the heart rate and the cardiac output statistically significantly decreased in both groups (paired t-test, p < 0.05). Arterial pressure did not change significantly. Stroke volume decreased and total peripheral resistance increased only in the group of subjects with a family history of hypertension (paired t-test, p < 0.05) The ingestion of L-arginine in predisposed normotensive subjects acutely improved the endothelium-dependent vasodilation (Dunnett’s test, p < 0.05), which is consistent with the assumption that endothelial dysfunction is already present in these subjects. Conclusions : In subjects with a family history of hypertension L-arginine improved endothelial function. This justifies L-arginine as a potential agent for the prevention and/or treatment of arterial hypertension.

High intensity interval training at overspeed in a lower body positive pressure treadmill improves performance in trained runners

Introduction: Exercise training of the lower limbs mediates localised conduit and resistance artery adaptations in the active region and systemic adaptations in the upper limbs. These changes to the vasculature are largelymediated through elevations in shear stress. Whether microcirculatory vascular responses to lower limb training occur systemically, and whether shear stress contributes to such adaptations, is currently unknown. Methods: Nine subjects completed an 8-week cycle ergometer training study, with unilateral cuff inflation around the forearm to unilaterally manipulate upper limb blood flow and shear stress during each exercise bout. To test skin microvascular function at 0, 4 and 8 weeks of exercise training, we measured laser-Doppler skin flux in response to localised disk heating at 33, 42 and 44 ◦C. Cutaneous vascular conductance was derived from skin flux and blood pressure values. Results: Acutely, the onset of cycling increased skin flux (12.1±4.1 to 131.7±35.0 PU) and temperature (31.7±0.4 to 33.6±0.9 ◦C), whilst in the cuffed arm (60mmHg) skin flux (11.91±2.22 to 52.92PU) and temperature (31.5±0.3 to 31.7±0.8 ◦C) responses were attenuated or absent (2-way ANOVA interaction-effect; both P<0.001). Chronically, after 8 weeks of cycling, skin flux responses during the plateau phase of heating at 42 ◦C (3.19±0.32 to 2.38±0.41PU/mmHg) and 44 ◦C (3.65±0.30 to 2.84±0.44PU/mmHg) were significantly lower in the uncuffed arm, but unchanged in the cuffed limb at (42 ◦C: 3.10±0.36 to 2.76±0.30PU/mmHg, 44 ◦C: 3.70±0.39 to 3.46±0.30PU/mmHg). Discussion: Cycling exercise is associated with increased skin perfusion in the upper limbs, an effect which is ameliorated by placement of a pressure cuff. Cycle training decreased the skin vasodilator response to an identical local heating stimulus, suggesting enlargement of the capillary bed and associated increase in skin blood flow transit time. We speculate that this impact of leg exercise training in the upper limbs may enhance systemic heat loss following training. No changes in the contra-lateral cuffed arm were apparent, suggesting that repeated increases in shear stress may mediate some of this adaptation in the skin microcirculation as a result exercise training.

Systemic adaptations to exercise training in skin microcirculation in humans

Introduction: Exercise training of the lower limbs mediates localised conduit and resistance artery adaptations in the active region and systemic adaptations in the upper limbs. These changes to the vasculature are largelymediated through elevations in shear stress. Whether microcirculatory vascular responses to lower limb training occur systemically, and whether shear stress contributes to such adaptations, is currently unknown. Methods: Nine subjects completed an 8-week cycle ergometer training study, with unilateral cuff inflation around the forearm to unilaterally manipulate upper limb blood flow and shear stress during each exercise bout. To test skin microvascular function at 0, 4 and 8 weeks of exercise training, we measured laser-Doppler skin flux in response to localised disk heating at 33, 42 and 44 ◦C. Cutaneous vascular conductance was derived from skin flux and blood pressure values. Results: Acutely, the onset of cycling increased skin flux (12.1±4.1 to 131.7±35.0 PU) and temperature (31.7±0.4 to 33.6±0.9 ◦C), whilst in the cuffed arm (60mmHg) skin flux (11.91±2.22 to 52.92PU) and temperature (31.5±0.3 to 31.7±0.8 ◦C) responses were attenuated or absent (2-way ANOVA interaction-effect; both P<0.001). Chronically, after 8 weeks of cycling, skin flux responses during the plateau phase of heating at 42 ◦C (3.19±0.32 to 2.38±0.41PU/mmHg) and 44 ◦C (3.65±0.30 to 2.84±0.44PU/mmHg) were significantly lower in the uncuffed arm, but unchanged in the cuffed limb at (42 ◦C: 3.10±0.36 to 2.76±0.30PU/mmHg, 44 ◦C: 3.70±0.39 to 3.46±0.30PU/mmHg). Discussion: Cycling exercise is associated with increased skin perfusion in the upper limbs, an effect which is ameliorated by placement of a pressure cuff. Cycle training decreased the skin vasodilator response to an identical local heating stimulus, suggesting enlargement of the capillary bed and associated increase in skin blood flow transit time. We speculate that this impact of leg exercise training in the upper limbs may enhance systemic heat loss following training. No changes in the contra-lateral cuffed arm were apparent, suggesting that repeated increases in shear stress may mediate some of this adaptation in the skin microcirculation as a result exercise training.

Increased Permeability of Cutaneous Lymphatic Capillaries and Enhanced Blood Flow in Psoriatic Plaques

Introduction: Morphological abnormalities of microvessels are described in psoriasis. However, there are conflicting data as to whether their function is also altered. Objective: Our aim was to study the morphology and function of the lymphatic capillaries of psoriatic skin. Methods: Morphology and permeability of initial lymphatics were studied by microlymphography and densitometry in 20 patients. Perfusion was studied by laser Doppler fluxmetry. Results: Permeability of lymphatics in plaques was increased by 7.6% compared to unafflicted skin (p < 0.001). Lymphatic vessel density and the extension of dye in lymphatic networks were not significantly different between involved and uninvolved areas. Both sites showed a wide range of diameters of lymphatics. The median laser Doppler flux in plaques was increased by 144% (91-380%) compared to unaffected skin (p < 0.001). Conclusions: Increased permeability of lymphatics and increased blood flow was demonstrated in vivo in psoriatic skin lesions. These findings may reflect the local inflammatory process and may be used as markers when studying new therapeutic approaches for psoriasis.

Choroidal circulation measurements by laser Doppler flux metry

AbstractContinuous real time Laser Doppler Flowmetry (LDF), has been used in humans, for the evaluation of the subfoveal choroidal circulation and the investigation of the regulatory processes of the choroidal blood flow in response to various physiological stimuli, as increases and decreases of the ocular perfusion pressure. A progressive decrease of the choroidal blood flow was observed with the aging and the progession of the age related macular degeneration. Abnormal regulation of the choroidal blood flow in patients suffering with neovascular AMD or Diabétic microangiopathy were also reported. The correlation of the subfoveal choroidal blood flow with the anatomical changes of the choroidal circulation as observed by OCT are under investigation.

Adenosine Effects on Renal Function in the Rat: Role of Sodium Intake and Cytochrome P450

Background/Aims: Adenosine (ADO) causes vasodilation in most tissues. In the kidney it can induce vasoconstriction or vasodilation, depending on the prevailing stimulation of A1 or A2 receptors (A1R, A2R). ADO-induced alterations of renal excretion may be secondary to haemodynamic changes, or reflect a direct influence on tubular transport. This whole-kidney study explored renal excretory responses to ADO receptor stimulation as related to renal haemodynamics sodium intake and cytochrome P450 (CYP-450) activity. Methods: The effects of ADO or an A2aR agonist (DPMA) on urine flow (V), sodium excretion (UNaV) and total solute excretion were examined in anaesthetized Wistar rats on a low-sodium or high-sodium (HS) diet. Total renal blood flow (RBF; renal artery probe), and outer- and inner-medullary blood flows (OM-BF, IM-BF; laser-Doppler fluxes) were also determined. Results: Consistent opposed effects of ADO and DPMA were only observed with the HS diet. ADO increased V (150%) and UNaV (100%); there were also significant increases in RBF, OM-BF and IM-BF. These changes were prevented by 1-aminobenzotriazol, a CYP-450 inhibitor. In HS rats, DPMA significantly decreased arterial blood pressure and renal excretion. Conclusions: Post-ADO diuresis/natriuresis was in part secondary to renal hyperperfusion; the response was probably mediated by CYP-450-dependent active agents. Selective A2aR stimulation induced systemic vasodilation, major hypotension, and a secondary decrease in renal excretion.

Oxidative Stress and Neuronal NOS Activity: Putative Determinants of Rapid Blood Pressure Increase After Renal Denervation in Anesthetized Rats

Long-term effects of renal denervation (DNX) commonly include a decrease in blood pressure (BP), observed in both normotensive animals and various models of hypertension. On the other hand, short term BP responses vary. We examined how post-DNX increase in BP observed in this study depends on baseline metabolic and functional status of animals, with a special interest for the role of oxidative stress. Anesthetized Wistar rats on standard (STD), low-sodium (LS) or high-sodium (HS) diet were used, untreated or pre-treated with tempol, a superoxide scavenger, or N(omega)-propyl-L-arginine (L-NPA), an inhibitor of neuronal NOS (nNOS). Early BP and renal hemodynamic responses were examined to right- and then left-side DNX performed using an own relatively non-invasive technique. Left kidney cortical, outer- and inner-medullary blood flows (CBF, OMBF, IMBF) were continuously recorded as laser-Doppler fluxes. Sequential denervations significantly increased BP to final 19 %, 12 %, and 6 % above control level in HS, LS, and STD groups, respectively. CBF, a measure of total renal perfusion, increased in LS and STD but not in HS rats. Tempol pretreatment prevented the post-denervation BP increase on each diet. Selective inhibition of nNOS prevented BP increase in STD and HS groups, a modest increase persisted in LS rats. We propose that enhanced afferent impulsation from intrarenal chemoreceptors related to oxidative stress in the kidney was the background for acute BP increase after DNX. The response was triggered by a release of brain sympatho-excitatory centers from inhibition by renal afferents, this was followed by widespread sympathetic cardiovascular stimulation.

Aspirin and Clopidogrel Alter Core Temperature and Skin Blood Flow during Heat Stress

Antithrombotic therapy with oral aspirin (ASA) or clopidogrel (CLO) (Plavix; Bristol-Myers Squibb, Bridgewater, NJ) is associated with an attenuated skin vasodilator response and a greater rate of rise in core temperature in healthy, middle-age individuals during passive heating in a water perfused suit. The present double-blind, crossover study examined the functional consequences of 7 d of low-dose ASA (81 mg·d) versus CLO (75 mg·d) treatment in 14 healthy, middle-age (50-65 yr) men and women during passive heating in air (40 min at 30°C, 40% relative humidity) followed by exercise (60% V˙O2peak). Oral temperature (Tor) was measured in the antechamber (23.0°C ± 0.1°C) before entering a warm environmental chamber. After 40 min of rest, subjects cycled on a recumbent cycle ergometer for up to 120 min. Esophageal temperature (Tes) and laser Doppler flux were measured continuously, and the latter was normalized to maximal cutaneous vascular conductance (%CVCmax). Before entry into the environmental chamber there were no differences in Tor among treatments; however, after 40 min of rest in the heat, Tes was significantly higher for ASA and CLO versus placebo (37.2°C ± 0.1°C, 37.3°C ± 0.1°C, vs 37.0°C ± 0.1°C, both P < 0.001), a difference that persisted throughout exercise (P < 0.001 vs placebo). The mean body temperature thresholds for the onset of cutaneous vasodilation were shifted to the right for both ASA and CLO during exercise (P < 0.05). ASA and CLO resulted in elevated core temperatures during passive heat stress and shifted the onset of peripheral thermoeffector mechanisms toward higher body temperatures during exercise heat stress.

Regional relation between skin blood flow and sweating to passive heating and local administration of acetylcholine in young, healthy humans

Regional variation in sweating over the human body is widely recognized yet variation in vasomotor responses and mechanisms causing this variation remain unclear. This study aimed to explore the relation between regional sweating rates (RSR) and skin blood flow (SkBF) responses to thermal and pharmacological stimuli in young, healthy subjects. In nine subjects (23 ± 3 yr), intradermal microdialysis (MD) probes were inserted into the ventral forearm, abdomen, thigh, and lower back and perfused with lactated Ringer solution. RSR over each MD membrane were measured using ventilated capsules with a laser Doppler probe housed in each capsule for measurement of red cell flux (laser Doppler flux, LDF) as an index of SkBF. Subjects completed a whole body heating protocol to 1°C rise in oral temperature and an acetylcholine dose response (ACh 1 × 10(-7)-0.1 M; mean skin temperature 34°C). Maximal LDF were obtained at the end of both protocols (50 mM sodium nitroprusside).During heating RSR varied among sites (P < 0.0001) and was greater on the back versus other sites (P < 0.05), but LDF was similar between sites (P = 0.343). RSR and SkBF showed a strong relation during initial (arm: r = 0.77 ± 0.09, thigh: r = 0.81 ± 0.08, abdomen: r = 0.89 ± 0.04, back: r = 0.86 ± 0.04) but not latter stages of heating. No differences in RSR (P = 0.160) or SkBF (LDF, P = 0.841) were observed between sites during ACh perfusion. Taken together, these data suggest that increases in SkBF are necessary to initiate and increase sweating, but further rises in RSR are not fully dependent on SkBF in a dose-response manner. Furthermore, RSR cannot be explained by cholinergic sensitivity or variation in SkBF.

Abstract TP262: Pulsed Electromagnetic Field (PEMF) Increases Microvascular Flow And Tissue Oxygenation In the Normal Rat Brain

Introduction: Pulsed Electromagnetic Field (PEMF) treatment has been shown to improve wound healing through increased nitric oxide levels. Thus, we hypothesized that PEMF improves microvascular (MV) flow and tissue oxygenation in the brain. Methods: Using in-vivo 2-photon laser scanning microscopy (2PLSM) over the parietal cortex of the normal rat brain, we measured MV red blood cell (RBC) flow velocity, diameters (range 3 to 15 μm which includes arterioles and venules), and tissue oxygenation (NADH fluorescence) before, during 30 minutes PEMF treatment and for three hours thereafter (three sessions with 30 min intervals). Doppler flux (0.9 mm probe diameter), arterial blood pressure, intracranial pressure, and arterial blood gases were concurrently monitored. Results: Microvascular flow velocities and diameters increased after PEMF treatment. Average MV diameters (300 MV measured in each of six rats) increased from 9.1±1.8 μm before to 9.4±2.1 μm during PEMF treatment (n=6, p&lt;0.05). Blood flow velocities also increased by 4.4±1.3 and 2.3±1.1 % during and after PEMF treatment respectively in comparison to baseline (p&lt;0.05). PEMF treatment decreased NADH autofluorescence indicating better tissue oxygenation and increased blood supply (96.1±2.4 and 98.2±1.3 % during and after PEMF treatment, respectively, compared to the baseline, p&lt;0.05). Laser Doppler flux averaged over a brain volume of 1 mm3 was unchanged before and during PEMF treatment. Conclusions: Thirty minutes of PEMF treatment induced MV dilation, increased RBC velocity and tissue oxygenation that persisted for 3 hours. Within the 3-hour period, however, MV diameters and RBC velocities gradually returned to baseline. Whether the effects observed are nitric oxide induced remains to be determined.

Impaired acetylcholine-induced cutaneous vasodilation in young smokers: roles of nitric oxide and prostanoids

Cigarette smoking attenuates acetylcholine (ACh)-induced cutaneous vasodilation in humans, but the underlying mechanisms are unknown. We tested the hypothesis that smokers have impaired nitric oxide (NO)- and cyclooxygenase (COX)-dependent cutaneous vasodilation to ACh infusion. Twelve young smokers, who have smoked more than 5.2 ± 0.7 yr with an average daily consumption of 11.4 ± 1.2 cigarettes, and 12 nonsmokers were tested. Age, body mass index, and resting mean arterial pressure were similar between the groups. Cutaneous vascular conductance (CVC) was evaluated as laser-Doppler flux divided by mean arterial pressure, normalized to maximal CVC (local heating to 43.0°C plus sodium nitroprusside administration). We evaluated the increase in CVC from baseline to peak (CVCΔpeak) and area under the curve of CVC (CVCAUC) during a bolus infusion (1 min) of 137.5 μM ACh at four intradermal microdialysis sites: 1) Ringer (control), 2) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combination of l-NAME + ketorolac. CVCΔpeak and CVCAUC at the Ringer site in nonsmokers were greater than in smokers (CVCΔpeak, 42.9 ± 5.1 vs. 22.3 ± 3.5%max, P < 0.05; and CVCAUC, 8,085 ± 1,055 vs. 3,145 ± 539%max·s, P < 0.05). In nonsmokers, CVCΔpeak and CVCAUC at the l-NAME site were lower than the Ringer site (CVCΔpeak, 29.5 ± 6.2%max, P < 0.05; and CVCAUC, 5,377 ± 1,109%max·s, P < 0.05), but in smokers, there were no differences between the Ringer and l-NAME sites (CVCΔpeak, 16.8 ± 4.3%max, P = 0.11; and CVCAUC, 2,679 ± 785%max·s, P = 0.30). CVCΔpeak and CVCAUC were reduced with ketorolac in nonsmokers (CVCΔpeak, 13.3 ± 3.6%max, P < 0.05; and CVCAUC, 1,967 ± 527%max·s, P < 0.05) and smokers (CVCΔpeak, 7.8 ± 1.8%max, P < 0.05; and CVCAUC, 1,246 ± 305%max·s, P < 0.05) and at the combination site in nonsmokers (CVCΔpeak, 15.9 ± 3.1%max, P < 0.05; and CVCAUC, 2,660 ± 512%max·s, P < 0.05) and smokers (CVCΔpeak, 11.5 ± 2.6%max, P < 0.05; and CVCAUC, 1,693 ± 409%max·s, P < 0.05), but the magnitudes were greater in nonsmokers (P < 0.05). These results suggest that impaired ACh-induced skin vasodilation in young smokers is related to diminished NO- and COX-dependent vasodilation.

Laser Doppler flux measurement for the assessment of cutaneous microcirculation – critical remarks

Back scattered Laser Doppler (LD) signals are composed of two different individual signals. The number of the moving particles and the speed of the particles in the measured tissue volume determine the frequency shift and the band width of the Doppler signal. The dependence of the Laser Doppler flux on the number of scattering particles is highly nonlinear: at very low hematocrit and high speed the axial migration of the cells to the centre of the blood vessels is very strong, so that in these cases - because of the parabolic flow profile - the Doppler flux measurement overestimates the mean real blood flow (up to two- or three-fold). The opposite is the case when the hematocrit is very high, then the blood flow might be underestimated (due to the increased amounts of blood cells near the vessel wall). In addition, a very change in number of moving particles - as can occur during the postprandial phase or during therapy - can change the signal also at a constant cell number. Also, it must be mentioned that the LD signal possibly is not only reflected by moving blood cells in the different skin layers but also by blood cells flowing in tissues below the skin (particularly below atrophied skin areas of older patients) so that in such cases the LD Flux signal reflects not exclusively the skin blood flow. Therefore, LD flux at rest may still be within the normal range even in advanced states of disease, since the scattered light is sampled from a tissue volume which may contain also non-nutritive shunt vessels. This critical analysis of the LD signals of course shall not lead to an overall rejection of the application of laser Doppler systems. Actual progress only can, however, be obtained under the exact consideration of anatomical conditions, technical restrictions and when generalizations are avoided.

Skin microvascular morphology and hemodynamics during treatment with veno-arterial extra-corporeal membrane oxygenation

To explore the potentials of microcirculatory assessments for predicting outcome of patients treated with extra corporeal membrane oxygenation for cardiogenic shock. Eight patients with acute cardiogenic shock treated with ECMO and eight healthy controls were examined with skin vital microscopy and laser Doppler perfusion measurements. Three patients died on ECMO (group 1). Five patients were successfully weaned off ECMO (group 2). Four patients were discharged from hospital and one died after successful weaning from bleeding complications. Patients surviving ECMO (group 2) had microcirculatory findings comparable with healthy controls. Patients in group 1 showed major skin microvascular pathology: pericapillary bleedings (n = 1), pericapillary dark haloes (n = 2) and capillary micro thrombi (n = 1). As compared with survivors they had lower functional capillary density (FCD) (n = 3), higher heterogeneity of functional capillary density (n = 3) and significantly reduced capillary mean flow-categorical velocity (n = 2). Laser Doppler measurements in group 1 had non-significant lower laser Doppler flux values as compared with survivors and controls. Skin microvascular pathology as detected with video microscopy (pericapillary bleedings or haloes, micro-thrombi/capillaries with "no flow", low FCD with high spatial distribution heterogeneity or low mean flow-categorial velocity) seems to be associated with poor prognosis.

Perfusion assessment in rat spinal cord tissue using photoplethysmography and laser Doppler flux measurements

Animal models are widely used to investigate the pathological mechanisms of spinal cord injury (SCI), most commonly in rats. It is well known that compromised blood flow caused by mechanical disruption of the vasculature can produce irreversible damage and cell death in hypoperfused tissue regions and spinal cord tissue is particularly susceptible to such damage. A fiberoptic photoplethysmography (PPG) probe and instrumentation system were used to investigate the practical considerations of making measurements from rat spinal cord and to assess its suitability for use in SCI models. Experiments to assess the regional perfusion of exposed spinal cord in anesthetized adult rats using both PPG and laser Doppler flowmetry (LDF) were performed. It was found that signals could be obtained reliably from all subjects, although considerable intersite and intersubject variability was seen in the PPG signal amplitude compared to LDF. We present results from 30 measurements in five subjects, the two methods are compared, and practical application to SCI animal models is discussed.

Positive end-expiratory pressure oscillation facilitates brain vascular reactivity monitoring

The pressure reactivity index (PRx) identifies optimal cerebral perfusion pressure after traumatic brain injury. We describe a method to improve PRx precision by induced variations in arterial blood pressure (ABP) using positive end-expiratory pressure (PEEP) modulation (iPRx). Neonatal swine (n = 10) were ventilated with static PEEP and then with PEEP oscillated between 5 and 10 cmH(2)O at a frequency of 1/min. PRx was recorded as a moving correlation coefficient between ABP and intracranial pressure (ICP) from spontaneous ABP activity (0.05-0.003 Hz) during static PEEP. iPRx was similarly recorded with PEEP oscillation-induced ABP waves. The lower limit of autoregulation (LLA) was delineated with continuous cortical laser Doppler flux monitoring. PEEP oscillation increased autoregulation-monitoring precision. The ratios of median absolute deviations to range of possible values for the PRx and iPRx were 9.5% (8.3-13.7%) and 6.2% (4.2-8.7%), respectively (P = 0.006; median, interquartile range). The phase-angle difference between ABP and ICP above LLA was 161° (150°-166°) and below LLA, -31° (-42° to 12°, P < 0.0001). iPRx above LLA was -0.42 (-0.67 to -0.29) and below LLA, 0.32 (0.22-0.43, P = 0.0004). A positive iPRx was 97% specific and 91% sensitive for perfusion pressure below LLA. PEEP oscillation caused stable, low-frequency ABP oscillations that reduced noise in the PRx. Safe translation of these findings to clinical settings is expected to yield more accurate and rapid delineation of individualized optimal perfusion-pressure goals for patients.

Peripheral vascular response to inspiratory breath hold in paediatric homozygous sickle cell disease

New Findings• What is the central question of this study?Autonomic nervous dysfunction is implicated in complications of sickle cell anaemia (SCA). In healthy adults, a deep inspiratory breath hold (IBH) elicits rapid transient SNS- mediated vasoconstriction detectable using Laser Doppler Flux (LDF) assessment of the finger-tip cutaneous micovasculature.• What is the main finding and its importance?We demonstrate significantly increased resting peripheral blood flow and sympathetic activity in African children with SCA compared to sibling controls and increased sympathetic stimulation in response to vasoprovocation with DIG.This study is the first to observe an inverse association between resting peripheral blood flow and haemoglobin oxygen saturation (SpO2). These phenomena may be an adaptive response to the hypoxic exposure in SCA.There is increasing evidence that autonomic dysfunction in adults with homozygous sickle cell (haemoglobin SS) disease is associated with enhanced autonomic nervous system-mediated control of microvascular perfusion. However, it is unclear whether such differences are detectable in children with SS disease. We studied 65 children with SS disease [38 boys; median age 7.2 (interquartile range 5.1–10.6) years] and 20 control children without symptoms of SS disease [8 boys; 8.7 (5.5–10.8) years] and recorded mean arterial blood pressure (ABP) and daytime haemoglobin oxygen saturation (). Cutaneous blood flux at rest (RBF) and during the sympathetically activated vasoconstrictor response to inspiratory breath hold (IBH) were measured in the finger pulp of the non-dominant hand using laser Doppler fluximetry. Local factors mediating flow motion were assessed by power spectral density analysis of the oscillatory components of the laser Doppler signal. The RBF measured across the two study groups was negatively associated with age (r=−0.25, P < 0.0001), ABP (r=−0.27, P= 0.02) and daytime (r=−0.30, P= 0.005). Children with SS disease had a higher RBF (P= 0.005) and enhanced vasoconstrictor response to IBH (P= 0.002) compared with control children. In children with SS disease, higher RBF was associated with an increase in the sympathetic interval (r=−0.28, P= 0.022). The SS disease status, daytime and age explained 22% of the variance in vasoconstrictor response to IBH (P < 0.0001). Our findings suggest that blood flow and blood flow responses in the skin of young African children with SS disease differ from those of healthy control children, with increased resting peripheral blood flow and increased sympathetic stimulation from a young age in SS disease. They further suggest that the laser Doppler flowmetry technique with inspiratory breath hold manoeuvre appears to be robust for use in young children with SS disease, to explore interactions between , ABP and autonomic function with clinical complications, e.g. skin ulceration.

75 Antitrombotic effect of polychromatic visible and infrared light in experimental model of thrombosis of main artery

Eleven adult patients with stable sickle cell disease (SCD) were investigated twice at a 15-day interval by nail fold capillaroscopy (NFC), bulbar conjunctival angioscopy (BCA), and laser Doppler flux metering (LDF). NFC and BCA are essentially descriptive. NFC revealed, in some patients, network patterns similar to those observed in vasculitis. BCA provides a reproducible method for the visual assessment of the microcirculation. When using a rating scale with five criteria it identified abnormalities related to both altered red blood cells and vascular morphology but failed to discriminate between patients. LDF, in contrast, is quantifiable and showed reproducible characteristic reactive alterations of vasomotion in response to ischemia after 3 min of occlusion. The SCD patients had a delayed response, best measured by the recovery half time, which was four to five times longer than that of normal subjects. In addition, the cold provocative test was always abnormal, as evidenced by a significant drop in the contralateral flux, and was often poorly tolerated. The observed trends suggest that BCA and LDF should be performed in a large cohort of patients, both in the steady state and during vasoocclusive crises. These methods seem to be useful complementary noninvasive procedures to cellular and clinical evaluation monitoring for therapeutic trials.