Laser Doppler Fluximetry Research Articles

Comparison in young White European (WE) and South Asian (SA) men of endothelium‐dependent cutaneous vasodilator responses: contribution of cyclooxygenase (COX) products

It is established that cardiovascular disease is more prevalent in South Asians (SA) than White Europeans (WE). The prevalence of diabetes central obesity and metabolic syndrome is particularly high in SAs, disorders that are associated with endothelial dysfunction. It is not known whether early markers of endothelial dysfunction can be detected even in young healthy SAs. Thus, we have compared responses evoked in recreationally‐active WE and SA men (18–25 years; n=10 in each case). SAs were 1st or 2nd generation residents in the UK with mother and father originating from India, Sri Lanka, Bangladesh or Pakistan; WEs were UK residents with WE parents. By using laser Doppler fluximetry, we monitored changes in cutaneous red cell flux (RCF) evoked in the cutaneous circulation of the forearm by iontophoresis of the endothelium‐dependent dilator acetylcholine (ACh, 8 × 20s pulses: 7 at 100 μA, 8th at 200 μA, at 60s intervals) and by release of arterial occlusion for 3 min (reactive hyperaemia). Responses were tested before and after aspirin (600mg p.o.) to assess the role of COX products. Mean arterial blood pressure (ABP) was continuously monitored by photoplethysmography using a finger cuff. Resting ABP was similar in WEs and SAs (124±1.8/70±1.7 vs 116.6±2.0/65.4±1.6 mmHg) and did not change during the protocol. Baseline RCF was also similar in WEs and SAs: 19.7±1.9 vs 12.3±0.9 perfusion units (PU), respectively. Further, ACh evoked similar dilator responses in WEs and SA, maximum RCF reaching 192.2±5.5 and 182.83 ± 5.20 perfusion units (PU) respectively. Aspirin had no net effect on ACh‐induced dilatation in either group (WEs: 182.6±4.5 and SAs: 193.0± 7.7 PU) indicating any influence of COX dilator and vasoconstrictor products was balanced in both WEs and SAs. By contrast, before aspirin, reactive hyperaemia was substantially larger in WEs than SA, peak RCF being 92.9±2.5 vs 74.2±3.1*PU, *: P<0.01 RMANOVA). Further, aspirin attenuated reactive hyperaemia in WEs, peak RCF being only 75.1 ± 2.6§PU: §: P<0.001 vs control response, but enhanced reactive hyperaemia in SAs, peak RCF reaching 84.7±2.7§PU. These results suggest that in young SA men, who have no overt signs of cardiovascular disease and are normotensive, there are already signs of endothelial dysfunction. Agonist‐evoked endothelium‐dependent dilatation is apparently normal in SAs with no net contribution from COX dilator or vasoconstrictor products, suggesting that nitric oxide and/or Endothelium‐dependent hyperpolarising factor are the main contributors in both ethnicities. However, reactive hyperaemia, which is induced by the combination of shear‐stress and metabolic stimuli, is blunted in young SAs relative to WEs and this is attributable to a predominating influence of vasoconstrictor COX products in SAs, but vasodilator COX products in WEs.Support or Funding InformationAlexander S. Onassis Public Benefit Foundation

Effect of diabetes on the cutaneous microcirculation of the feet in patients with intermittent claudication.

To evaluate endothelial-dependent and - independent cutaneous vasodilator responses in the feet of patients with peripheral arterial disease (PAD) with or without Type 2 diabetes. Cutaneous microvascular responses in the dorsum of both lower limbs were measured in the supine position using Laser Doppler Fluximetry combined with iontophoretic administration of endothelial-dependent (acetylcholine, Ach) and -independent (sodium nitroprusside, SNP) vasodilators in diabetic (n = 19) and non diabetic (n = 17) patients with PAD (presenting as unilateral calf intermittent claudication (IC). In patients with diabetes and IC, endothelial-dependent vasodilation was significantly impaired in the symptomatic limb [74 (57,105) vs 68 (24,81) PU, Z =-2.79, p = 0.005] compared to the asymptomatic limb. Patients without diabetes showed no impairment of vasodilation. Resting ankle-brachial pressure index did not identify the presence of abnormalities in microvascular function. The combination of diabetes and PAD is associated with a reduction in endothelial-dependent cutaneous vasodilation in the feet without an associated reduction in endothelial independent vasodilation.

The effects of Secondhand Smoke (SHS) exposure on microvascular endothelial function among healthy women.

BackgroundStudies have demonstrated that secondhand smoke (SHS) exposure could impair endothelial function. However, the effect of SHS exposure specifically on microvascular endothelial function is not well understood. This study aimed to determine the effects of SHS exposure on microvascular endothelial function among non-smoking, generally healthy women.FindingsWe studied 127 women; and based on their hair nicotine levels measured using gas chromatography-mass spectrometry, 25 of them were categorized as having higher hair nicotine levels, 25 were grouped as having lower hair nicotine and 77 women were grouped into the non-detected group. The non-detected group did not have detectable levels of hair nicotine. Anthropometry, blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured accordingly. Microvascular endothelial function was assessed non-invasively using laser Doppler fluximetry and the process of iontophoresis involving acetylcholine and sodium nitroprusside as endothelium-dependent and endothelium-independent vasodilators respectively. The mean hair nicotine levels for higher and lower hair nicotine groups were 0.74 (1.04) and 0.05 (0.01) ng/mg respectively. There were no significant differences in anthropometry, BP, lipid profile and hsCRP between these groups. There were also no significant differences in the microvascular perfusion and endothelial function between these groups.ConclusionIn this study, generally healthy non-smoking women who have higher, lower and non-detected hair nicotine levels did not show significant differences in their microvascular endothelial function. Low levels of SHS exposure among generally healthy non-smoking women may not significantly impair their microvascular endothelial function.

The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function

Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR). 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations. 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group. 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.

Microvascular reactivity in women with gestational diabetes mellitus studied during pregnancy.

AimTo compare microvascular reactivity assessed in the skin using laser Doppler fluximetry (LDF) in women with gestational diabetes mellitus (GDM) and gestational age-matched control during pregnancy.Methods110 pregnant women at ~33 weeks gestation participated in the study. Skin microvascular reactivity was evaluated by LDF, at rest, during the response to brief arterial occlusion (post occlusive hyperaemic response) and during sympathetically mediated vasoconstrictor response to deep inspiratory breath hold.ResultsNo statistically significant differences were found in the microvascular variables studied (resting and maximum rate flux, post-ischaemic reactive hyperaemia and deep inspiratory breath holds) between +GDM and –GDM groups women. In women with GDM there was a negative correlation between resting flux and the response to the oral glucose tolerance test (OGTT), r = -0.282 (p = 0.037). There was also a negative correlation between the response to the OGTT and the sympathetically mediated constrictor response to inspiratory breath holds (r = -.298, p = .030) but not in women with GDM (r = .102, r = .468).ConclusionAttenuated microvascular reactivity as an early marker of endothelial dysfunction is not present in women with GDM when assessed during pregnancy.

Long-term effects of an exercise and Mediterranean diet intervention in the vascular function of an older, healthy population

BackgroundPreserving endothelial function and microvascular integrity is suggested to reduce cardiovascular disease risk. It was recently shown that the age-dependent decline in endothelial and microvascular integrity may be reversed when combining exercise with Mediterranean diet (MD) in an 8-week intervention. The present study investigates whether the risk-reduction improvement in microcirculatory and cardiorespiratory functions are sustained in this age-group after a 1-year follow-up. Design and methodsTwenty sedentary healthy participants (age, 55±4years) from the original study underwent cardiopulmonary exercise tolerance test and were assessed for their upper- and lower-limb vascular endothelial cutaneous vascular conductance (CVC) using laser Doppler fluximetry (LDF) with endothelium-dependent [ACh (acetylcholine chloride)] and endothelium-independent [SNP (sodium nitroprusside)] vasodilation, 1year after completing the intervention. ResultsBoth MD and exercise groups appeared to have an improved microvascular responses, in comparison to baseline as far as ACh is concerned. Exploring the interactions between the time point and the original group, however, revealed a stronger improvement in the MD group in comparison to the exercise group, for ACh (p=0.04, d=0.41). In the upper body, the time point and group interaction for ACh, indicated a better improvement for MD, without however statistical significance (p=0.07, d=0.24). Additionally, cardiorespiratory improvement in ventilatory threshold was maintained, 1year after (12.2±3.0 vs. 13.2±3.2ml∙kg−1∙min−1, p<0.05). ConclusionsThe original improvements from an 8-week exercise and MD intervention were still evident, particularly in the microcirculatory and cardiorespiratory assessments, 1year after the initial study. This suggests that a brief intervention combining MD with exercise in this high-risk group promises long-term health benefits.

Impact of long-term exposure to cigarette smoking on skin microvascular function

In order to evaluate the impact of cigarettes smoking and smokers' clinical characteristics on skin microvascular function, we measured the skin forearm blood flux, basally and during post-occlusive reactive hyperaemia, in 100 current smokers (mean age 51±11years; range: 18 to 86years) and in 66 healthy never-smokers matched for age and sex, by using laser Doppler fluximetry (LDF). Basal and post-ischemic LDF tracings were analyzed in the frequency domain within 0.009–0.02Hz, 0.021–0.06Hz and 0.061–0.2Hz ranges, related to endothelial-dependent, sympathetic-dependent and myogenic-dependent vasomotion, respectively, using an adapted version of the Fourier analysis. The post-ischemic percentage change from baseline of the area under the LDF curve (AUC%) was significantly lower in smokers than in never-smokers [162.5% (139.3–183.0) vs 190.1% (156.3–216.8); p=0.00016]. Compared to controls, smokers also showed a reduced basal power spectral density (PSD) in the myogenic-dependent vasomotion (p=0.0034) and a reduced post-ischemic percentage increase in PSD of the endothelial-dependent vasomotion (p=0.0010) and sympathetic-dependent vasomotion (p=0.0016). An inverse relationship was observed in smokers between AUC% and smoking exposure duration (r=0.23, p=0.018), pack-years (r=0.33, p=0.0007), age (r=0.26, p=0.008) and body mass index (r=0.21, p=0.037). In the multiple linear regression model, pack-years was the only variable independently associated with AUC% (r=0.21, p=0.03). This study confirms that smoking is associated with cutaneous microvascular dysfunction and shows that the severity of this impairment is independently related to the duration and intensity of the exposure to smoking.

Effects of exercise training and Mediterranean diet on vascular risk reduction in post-menopausal women

This study tested the potential risk-reduction benefits of Mediterranean Diet (MD) and regular exercise training on microvascular activity and cardiorespiratory capacity in postmenopausal women. Fifteen sedentary postmenopausal participants (age = 54.6 ± 3.6) were randomised into either exercise training or exercise combined with following MD for eight-weeks, and were assessed for their cardiorespiratory capacity, and upper- and lower-limb endothelial cutaneous vascular conductance (CVC) test using Laser Doppler Fluximetry (LDF), coupled with measuring endothelium-dependent Acetylcholine Chloride (Ach) and -dependent Sodium Nitropurruside (SNP) vasodilators. Exercise training improved cardiorespiratory capacity as indicated by ventilatory threshold (11.5 ± 2.1 vs. 14.0 ± 3.0 ml·kg-1·min-1, p < 0.05) and improved the microcirculatory perfusion results of CVC for both vasodilators Ach (p < 0.001, d = 0.65) and SNP (p = 0.003, d = 0.53) in the lower-limb and ACh (p = 0.01, d = 0.41) and SNP (p = 0.03, d = 0.48) in the upper-limb, all (p < 0.05). However, combining exercise with MD showed a stronger improvement in Ach (p = 0.02, d = 0.36) of the lower limb, than in exercise alone group. The results suggest that regular moderate exercise improves microcirculatory vascular function and increases exercise tolerance, both are responsible for reducing cardiovascular risk in postmenopausal women. However, combining MD with exercise suggests additional microvascular vasodialiatory improvement, suggesting an effective strategy for further cardiovascular risk-reduction in this high-risk group.

Attenuated Systemic Microvascular Function in Men with Coronary Artery Disease is Associated with Angina but not Explained by Atherosclerosis

Refractory angina is the occurrence of clinical symptoms despite maximal therapy. We investigated associations between microvascular function, atherosclerotic burden, and clinical symptoms in subjects with CAD. Skin microvascular response to heating and ischemia was assessed in 167 male volunteers by laser Doppler fluximetry; 82 with CAD on maximal therapy and 85 with no known CAD (noCAD). CAC scores, carotid IMT, and femoral IMT were measured and symptoms were scored using the Rose angina questionnaire. Patients with CAD had poorer microvascular response to heating (114[95% CI 106-122]au CAD vs. 143[134-153]au no CAD; p < 0.0001) and ischemia (42[38-46]au CAD vs. 53[78-58]au. noCAD; p = 0.001). Thirty-eight percent of the noCAD group had elevated CAC scores. There were no associations between markers of atherosclerosis and microvascular function. Forty-two percent of the CAD group had refractory angina. This was associated with impaired microvascular function compared to those with elevated CAC scores but no symptoms (109 [95-124]au vs. 131[122-140]au; p = 0.008). Men with symptomatic CAD have poorer microvascular function compared to individuals without CAD. Microvascular function does not correlate with atherosclerosis, but is impaired in individuals with refractory angina. Microvascular dysfunction may play a role in the symptomatology of angina.

Impaired skin microcirculation in paediatric patients with type 1 diabetes mellitus

Aims/hypothesisWe used Laser Doppler Fluximetry (LDF) to define "normal" endothelial function in a large cohort of healthy children and adolescents and to evaluate skin microcirculation in paediatric patients with type 1 diabetes mellitus.MethodsLDF was performed in 102 healthy children (12.8 ± 3.3 years of age; 48 male) and 68 patients (12.9 ± 3.3 years of age; 33 male). Duration of disease was 5.0 ± 3.97 years. Each participant sequentially underwent three stimulation protocols (localized thermal hyperaemia with localized warming to maximum 40°C, iontophoretic delivery of pilocarpine hydrochloride (PCH) and sodium nitroprusside (SNP)). The maximum relative increase in skin blood flow and the total relative response, i.e. the area under the curve (AUC) to each stimulus (AUCheat, AUCPCH, AUCSNP) was determined. In addition, the area of a right-angled triangle summarizing the time to and the amplitude of the first peak, which represents the axon reflex mediated neurogenic vasodilation (ARR) was calculated.ResultsIn healthy controls, AUCheat, AUCPCH, AUCSNP, and ARR turned out to be independent of sex, age, and anthropometric values. Per parameter the 10th percentile generated from data of healthy controls was used as the lower threshold to define normal endothelial function. Diabetic patients showed significantly reduced vasodilatative response to either physical or pharmacological stimulation with SNP, whereas the response to PCH was comparable in both cohorts. In patients compared to controls i) a significantly higher frequency of impaired vasodilatation in response to heat and SNP was noted and ii) vascular response was classified as pathological in more than one of the parameters with significantly higher frequency.Conclusions/interpretationSkin microvascular endothelial dysfunction is already present in about 25% of paediatric type 1 diabetic patients suffering from type 1 diabetes for at least one year. Future studies are needed to assess the predictive value of endothelial dysfunction in the development of long-term (cardio)vascular comorbidity in these patients.

Blood pressure rises more in pre-eclampsia than normal pregnancy when acral skin is locally cooled

Objective: Investigate blood pressure response to acral skin vasoconstriction in healthy and pre-eclamptic pregnancies. Methods: Healthy women were investigated from gestational week 8 to 52 weeks postpartum and pre-eclampsia subjects at diagnosis. Finger artery ultrasound Doppler, forearm laser Doppler fluximetry and photoplethysmographic blood pressure were recorded. Hand cooling to 19 °C induced vasoconstriction. Results: Acral skin vasoconstriction increases blood pressure from 16 weeks until 12 weeks postpartum (p ≤ 0.01), with greatest responses in pre-eclampsia (p = 0.047). Forearm skin perfusion is higher in pre-eclampsia (p = 0.04). Conclusion: Acral skin vasoconstriction raises blood pressure in pregnancy, particularly in pre-eclampsia. Pregnancy accentuates important functional differences within skin.

Impaired microvascular endothelial function in vitamin D-deficient diabetic nephropathy patients

This study aims to compare microvascular endothelial function between vitamin D-deficient and nondeficient groups of patients with diabetic nephropathy. Serum levels of the inflammatory marker high-sensitivity C-reactive protein (hsCRP) were also measured. This prospective cross-sectional study involved 70 patients with diabetic nephropathy; 40 were categorized into the group with nondeficient serum 25-hydroxyvitamin D levels [25(OH)D >50 nmol/l], whereas 30 patients were categorized to the group with deficient serum 25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and sodium nitroprusside were used to determine endothelium-dependent and independent vasodilatation. Mean age of patients was 56.7 ± 3.8 years; 50 were men, whereas 20 were women. Mean serum 25(OH)D in the vitamin D-nondeficient group was 69.4 ± 2.9 nmol/l; the level in the vitamin D-deficient group was 42.1 ± 1.3 nmol/l, P < 0.001. Endothelium-dependent vasodilatation was lower in the vitamin D-deficient group compared with the vitamin D-nondeficient group (23.6 ± 2.7 versus 37.3 ± 3.8 arbitrary units, P = 0.004). No significant differences were observed between the two groups in their hsCRP levels, mean age, estimated glomerular filtration rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and glycosylated haemoglobin. Microvascular endothelial function was significantly reduced in diabetic nephropathy patients with deficient vitamin D levels compared with those with nondeficient levels.

Contributions of cyclooxygenase (COX) and NO synthase (NOS) pathways to endothelium‐dependent dilatation in the finger of women

We tested the roles of COX and NOS in finger vasodilatation evoked by iontophoresis of acetylcholine (ACh), using laser Doppler fluximetry. In 12 women in the low oestrogen (E2) phase of the menstrual cycle, aspirin (600mg p.o) decreased baseline finger red cell flux (RCF) from 55.0±7.8 to 30.6±5.5* perfusion units (pu; *: P&lt;0.05), and the ACh‐evoked response from +296.8±23.9 to +251.4±24.4* pu. In the high E2 phase, COX inhibition decreased baseline from 68.0 ± 13.8 to 38.4 ± 8.1*, but had no effect on the ACh response (259.5±27.4 vs 251.2±23.3 pu). On different days, NOS inhibition with L‐NAME had no effect on baseline RCF in the low, or high E2 phase. In the low E2 phase, the ACh response was unchanged (+228.26±25.8 vs 225.6±21.3pu), but aspirin then decreased the response further to 175.9±17.6*pu. In the high E2 phase, L‐NAME increased the ACh response from +198.1±23.7 to +229.2±27.4*pu; COX inhibition restored it to +202.8±27.8pu. We propose that in the finger, NOS generates both NO and O2− and thereby, ONOO− which inhibits PGI2 synthase. E2 facilitates NOS and PGI2 synthase such that when E2 is high, PGI2 contributes to endothelium‐dependent finger dilatation only after NOS inhibition.

Mediterranean diet- and exercise-induced improvement in age-dependent vascular activity

The aging effect on microvascular integrity, marked by endothelial dysfunction and reduction in exercise tolerance, is a major cause of CVD (cardiovascular disease). Improved dietary habits, known to reduce morbidity and mortality, are also known to attenuate those aging effects. The present study investigated the effects of combined MD (Mediterranean diet) and exercise intervention on lower- and upper-limb cutaneous microvascular functions in an older healthy population. A total of 22 sedentary healthy participants (age, 55±4 years) underwent cardiopulmonary exercise tolerance test, and were assessed for their upper- and lower-limb vascular endothelial CVC (cutaneous vascular conductance) using LDF (laser Doppler fluximetry) with endothelium-dependent [ACh (acetylcholine chloride)] and -independent [SNP (sodium nitroprusside)] vasodilation. Participants were then randomized into two groups: MD and non-MD, and followed an 8-week intervention programme, which included discontinuous treadmill running based on each individual's exertion, twice per week. Exercise training improved CVC in both groups (e.g. 0.42±0.19 compared with 1.50±1.05 and 0.47±0.26 compared with 1.15±0.59 at 1000 μCb for MD and non-MD respectively; P<0.001). This was also combined by improvement in the exercise tolerance indicated by increased VT (ventilatory threshold) in both groups [12.2±2.8 compared with 14.8±2.8 ml·(kg of body weight)(-1)·min(-1) and 11.7±2.7 compared with 14.6±3.2 ml·(kg of body weight)(-1)·min(-1) for MD and non-MD groups respectively; P<0.05]. However, the MD group showed greater improvement in endothelium-dependent vasodilation than non-MD [ANCOVA (analyses of co-variance), P=0.02]. The results of the present study suggest that compliance with MD, combined with regular moderate exercise, improves age-provoked microcirculatory endothelial dysfunction and increases exercise tolerance, both responsible for reducing cardiovascular risk in this age group.

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.

408 VITAMIN D INSUFFICIENCY WORSENS MICROVASCULAR ENDOTHELIAL FUNCTION IN DIABETIC NEPHROPATHY PATIENTS

Objectives: This study aims to compare microvascular endothelial function between vitamin D sufficient and insufficient groups of patients with diabetic nephropathy. Serum levels of the inflammatory marker high sensitivity C-reactive protein (hsCRP) was also measured. Designs and Methods: This prospective cross sectional study involved 70 patients with diabetic nephropathy; 40 were categorised into the group with sufficient serum 25-hydroxyvitamin D levels (serum 25(OH)D>50 nmol/l) while 30 patients were categorised to the group with insufficient serum 25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using Laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and sodium nitroprusside were used to assess endothelium dependent and independent vasodilatation. Results: Mean age of patients in this study was 56.7 ± 3.8 years; 50 were males while 20 were females. Mean serum 25(OH)D in the vitamin D sufficient group was 69.4 ± 2.9nmol/l whilst in vitamin D insufficient group was 42.1 ± 1.3 nmol/l, p < 0.001. Endothelium dependent vasodilatation was lower in vitamin D insufficient group compared to vitamin D sufficient group (23.6 ± 2.7 vs. 37.3 ± 3.8 AU, p= 0.004) indicating impairment in microvascular endothelial function in vitamin D insufficient group. Significant reduction in percentage change of Acetylcholine (ACh) was also seen in vitamin insufficient groups compared to vitamin D insufficient group [209.7 ± 471 vs. 527 ± 392.25, p = 0.0045]. No significant differences were observed between the two groups in their hsCRP, mean age, estimated glomerular filtration rate, systolic and diastolic blood pressure and glycosylated haemoglobin Conclusion: Microvascular endothelial function was significantly reduced in diabetic nephropathy patients with insufficient vitamin D levels.

Obesity indices and metabolic markers are related to hs-CRP and adiponectin levels in overweight and obese females

Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects.

Randomized controlled trial of laparoscopic gastric ischemic conditioning prior to minimally invasive esophagectomy, the LOGIC trial

Minimally invasive esophagectomy (MIE) is a viable alternative to open resection for the management of esophagogastric cancer. However, the technique may relate to a higher incidence of ischemia-related gastric conduit complications. Laparoscopic ischemic conditioning (LIC) by ligating the left gastric vessels 2 weeks before MIE may have a protective role, possibly through an improvement of conduit perfusion. This project was designed to evaluate whether LIC influenced ultimate conduit perfusion. A randomized controlled trial was designed to compare MIE with LIC (L) against MIE without (N). The project began in May 2009 and was offered to consecutive patients with the objective of recruiting 22 in each arm. Sample size calculations were based on data from previous clinical series. The main outcome measure was perfusion recorded by validated laser Doppler fluximetry, at the fundus (F) and greater curve (G); performed at routine staging laparoscopy and every stage of an MIE. A perfusion coefficient measured as ratio at stage of MIE over baseline was used for statistical analysis. Sixteen patients were recruited before an interim analysis of the trial data. At staging laparoscopy perfusion at F was higher than at G (p = 0.016). In the L cohort, an apparent rise in perfusion at G is observed post intervention (p = 0.176). At MIE, baseline perfusion is comparable for both arms; however, a significant drop is observed at both locations once the stomach is mobilized and exteriorized (p = 0.001). Once delivered at the neck, perfusion coefficient is approximately 38% of baseline levels. However, there was no discernible difference between the L (38.3 ± 12) and N (37.7 ± 16.8) cohorts (p = 0.798). LIC does not translate into an improved perfusion of the gastric conduit tip. The benefits reported from published clinical series suggest that the resistance of the conduit to ischemia occurs through alternative possibly microcellular mechanisms.

Impaired post-ischaemic microvascular hyperaemia in Indian Asians is unexplained by diabetes or other cardiovascular risk factors

ObjectivePeople of Indian Asian descent have an increased risk of cardiovascular disease (CVD) that cannot be explained by diabetes and other established CVD risk factors. We investigated if microcirculatory function was impaired in a population-based sample of people of Indian Asian descent compared with Europeans in the UK and whether any differences could be accounted for by diabetes or other CVD risk factors. Research design and methodsCutaneous microvascular function was assessed using laser Doppler fluximetry in response to heating to 42°C (maximum hyperaemia) and 3min arterial occlusion (post occlusive reactive hyperaemia: PORH) in 148 Indian Asians and 147 Europeans. Blood pressure, anthropometry and fasting bloods were also measured. ResultsMaximum hyperaemia and minimum resistance did not differ significantly by ethnicity. Resting flux and PORH were lower in Indian Asians and time to peak of PORH was prolonged. Diabetes was associated with reduced maximum hyperaemia and PORH. Adjustment for diabetes accounted for differences in resting flux and time to peak but not differences in PORH (Europeans=45.0 (40.3, 50.1)au, Indian Asians=35.6 (31.9, 39.7)au, mean (95% confidence interval); p=0.008 after adjustment). Differences in conventional CVD risk factors did not account for interethnic differences in microvascular responses. ConclusionsPeople of Indian Asian descent have impaired post-occlusive reactive hyperaemia unexplained by diabetes, dysglycaemia or other CVD risk factors. Abnormal microvascular function in response to ischaemia could represent a novel mechanism contributing to the elevated risk of CVD in Indian Asians.

Effects of Lower Limb Angioplasty on Endothelial-Dependent and -Independent Microvascular Reactivity

BackgroundPercutaneous Transluminal Angioplasty (PTA) of the lower limb improves arterial flow and claudication symptoms, but the effects on cutaneous microvascular perfusion and reactivity have not been previously reported. ReportCutaneous microvascular function in the feet was assessed in 12 patients with intermittent claudication before and after PTA using Laser Doppler Fluximetry (LDF) with transcutaneous iontophoretic administration of acetylcholine and sodium nitroprusside. Maximum vasodilator responses to both endothelial-dependent and independent vasodilators were increased following PTA. ConclusionsLarge vessel intervention to improve macrovascular flow has additional benefits on the downstream cutaneous microcirculation to improve vasodilator responsiveness. These effects may be clinically important to reduce the risk of ischaemic ulceration and tissue breakdown.