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Venous endothelial function in postmenopausal women who are receiving long-term estrogen and progestagen therapy.

OBJECTIVE: To test venous endothelial function during long-term hormone replacement therapy (HRT) and after treatment withdrawal. DESIGN: Measurement of dorsal hand-vein diameter by venous occlusion plethysmography during infusion of norepinephrine, bradykinin, NG-monomethyl L-arginine, and sodium nitroprusside. SETTING: Plethysmography and menopause units, University Hospital Marqués de Valdecilla, Santander, Spain. PATIENT(S): Twenty postmenopausal women, of whom 10 were assigned to receive no hormone replacement therapy (HRT) for 6 months after plethysmography (group A) and 10 were assigned to receive HRT for 6 months (group B). After 6 months, HRT was administered to group A and withdrawn from group B for another 6 months. INTERVENTION(S): Plethysmography at baseline and at 6 and 12 months. MAIN OUTCOME MEASURE(S): Dorsal hand-vein diameter measured by venous occlusion plethysmography during infusion of norepinephrine, bradykinin, NG-monomethyl L-arginine, or sodium nitroprusside. RESULT(S): At 6 months, the maximum dilation obtained with bradykinin was 48.8 +/- 7.58% in group A and 76.7 +/- 12.9% in group B. At 12 months, maximum bradykinin dilation increased to 74.3 +/- 14.2% in group A and decreased to 54.0 +/- 15.9% in group B. CONCLUSION(S): Long-term HRT with estrogen plus progestin improves endothelium-dependent vasodilation, but this effect is lost in a relatively short time. Endothelial function in dorsal hand veins is an easy-to-use plethysmography model that can be used in serial studies.

Bradykinin↗

Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise.

OBJECTIVES: To assess subclinical inflammation, fasting insulin, and endothelial function before and after exercise in overweight children and adolescents. STUDY DESIGN: Twenty-five children (body mass index [BMI] >85th percentile) were assessed for brachial artery flow-mediated dilation (FMD), nitroglycerin-induced dilation, C-reactive protein (CRP), lipids, glucose, insulin, oral glucose tolerance, body composition, aerobic fitness (peak oxygen uptake [VO 2 peak]), and blood pressure. Twenty of these persons were equally and randomly assigned to either 8 weeks of stationary cycling or to a non-exercising control group. RESULTS: A baseline correlation was found between CRP and fasting insulin (r = 0.62; P < .001), which remained significant after adjusting for baseline variables (r = 0.53; P < .05). After 8 weeks, significant improvements were observed in the exercise group compared with the control group for VO 2 peak (exercise group = 21.8 +/- 2.1 to 23.2 +/- 1.5 mL/kg/minute vs control group = 23.4 +/- 1.6 to 20.9 +/- 2.2 mL/kg/minute; P < .05), high-density lipoprotein (HDL) cholesterol (exercise group = 1.02 +/- 0.03 to 1.10 +/- 0.04 mmol/L vs control group = 1.08 +/- 0.07 to 0.99 +/- 0.09 mmol/L; P < .05), and FMD area under the curve (AUC) (exercise group = 746 +/- 66 to 919 +/- 94 %*sec vs control group = 731 +/- 102 to 515 +/- 73 %*sec; P < .05). CONCLUSIONS: In overweight children and adolescents, CRP is independently associated with fasting insulin. Eight weeks of aerobic exercise improves fitness, HDL cholesterol, and endothelial function in this group.

Adolescent↗

The effects of hormone replacement therapy on endothelial function in women with Turner's syndrome.

OBJECTIVES: To examine the effect of hormone replacement therapy (HRT) on endothelial function of forearm resistance vessels in women with Turner's syndrome. DESIGN: Subjects were studied on three occasions: on their usual HRT (study 1), then after 6 weeks off HRT (study 2) and finally after a further 6 weeks on HRT (study 3). PATIENTS: Seven young women with Turner's syndrome were studied. MEASUREMENTS: Forearm blood flow in response to intrabrachial infusion of bradykinin, 10, 30, 100 pmol/min (endothelium-dependent vasodilator), glyceryl trinitrate, 4, 8, 16 nmol/min (GTN; endothelium-independent vasodilator), noradrenaline, 60, 120, 240 pmol/min (NA, alpha-adrenergic receptor agonist) and NG-monomethyl-l-arginine, 1, 2, 4 micromol/min (L-NMMA; NO synthase inhibitor) was assessed by bilateral venous plethysmography. RESULTS: The vasodilator response to bradykinin, expressed as the within-subject mean difference in area under the dose-response curve between study 2 and study 1, was significantly diminished (-744.2 +/- 287.2, P = 0.04) but improved 6 weeks after HRT recommencement. However, there was no significant change in response to GTN (between study 2 and study 1, 189.5 +/- 247.8, P = 0.47). The vasoconstrictor response to L-NMMA was also diminished in study 2 when compared to study 1 (-100.4 +/- 35.4, P = 0.039) and was restored after HRT was recommenced (between study 3 and study 2, 117.5 +/- 69.3, P = 0.17) whereas there was no significant difference in response to NA between study 2 and study 1 (76.7 +/- 50.6, P = 0.18) or study 3 and study 2 (-70.8 +/- 71.1, P = 0.38). CONCLUSIONS: HRT improves endothelial function in women with Turner's syndrome.

Adult↗

Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia.

High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule [ICAM-1], E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 +/- 10 years, waist/hip circumference ratio 0.89 +/- 0.07, LDL-cholesterol [LDL-c] 4.9 +/- 1.3 mmol/L, triglycerides 1.8 +/- 0.9 mmol/L, HDL-c 1.3 +/- 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v >or= 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P <.05), higher triglycerides (P <.001), higher body mass index (P <.02), lower FMV (3.7% +/- 2.0% v 4.9% +/- 3.4%, P <.002), higher VCAM-1 (1,195 +/- 395 ng/mL v 984 +/- 303 ng/mL, P <.01), and higher ICAM-1 (406 +/- 78 ng/mL v 364 +/- 68 ng/mL, P <.01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P =.003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P <.05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules.

Adult↗

Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes.

Endothelial dilator function is impaired in people with type 2 diabetes mellitus (T2DM). Prior research indicates that this can be improved with intravenous administration of ascorbate or L-arginine, but whether these agents have this effect when administered by the clinically practical oral route is unknown. To investigate this question, 10 premenopausal women with T2DM and 10 healthy, premenopausal, non-diabetic women received, in random sequence, a 1-week administration of oral L-arginine (9 g daily) or vitamins E (1800 mg) and C (1000 mg) with an intervening 1-week washout period. Flow-mediated brachial artery dilation (FMD) was measured by ultrasonography and forearm blood flow was measured by plethysmography before and following blood pressure cuff-induced forearm ischemia before and after each week of treatment. At baseline, the women with T2DM had lesser FMD responses (0.028 +/- 0.006 cm vs 0.056 +/- 0.008 cm, p < 0.05). Post-ischemic forearm hyperemia was reduced at baseline in T2DM compared with controls (16.4 +/- 1.8 vs 26.0 +/- 1.4 ml 100 ml(-1) min(-1), p < 0.05). Administration of L-arginine caused a 50 +/- 12% increase in FMD in T2DM (p < 0.05) and raised post-ischemic forearm blood flow by 29 +/- 8% (p < 0.05). No significant changes were seen in controls. Administration of vitamins E and C in women with T2DM produced an increase in the brachial artery diameter response of 79 +/- 15% (p < 0.05), but did not significantly increase the hyperemic blood flow response (p = NS). No significant changes in the responses of controls from pre to post vitamin administration were observed. We concluded that administration of two types of oral agents improved measures of endothelial function in people with T2DM.

Administration, Oral↗

Effect of acute ketosis on the endothelial function of type 1 diabetic patients: the role of nitric oxide.

In type 1 diabetic patients, acute loss of metabolic control is associated with increased blood flow, which is believed to favor the development of long-term complications. The mechanisms for inappropriate vasodilation are partially understood, but a role of endothelium-derived nitric oxide (NO) production can be postulated. We assessed, in type 1 diabetic patients, the effect of the acute loss of metabolic control and its restoration on forearm endothelial function in 13 type 1 diabetic patients who were studied under conditions of mild ketosis on two different occasions. In study 1, after basal determination, a rapid amelioration of the metabolic picture was obtained by insulin infusion. In study 2, seven type 1 diabetic patients underwent the same experimental procedure, except that fasting plasma glucose was maintained constant throughout. Basal plasma venous concentrations of nitrites/nitrates (NO2- + NO3-) were determined both before and after intravenous insulin infusion. Endothelium-dependent and -independent vasodilation of the brachial artery was assessed by an intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) and sodium nitroprusside (SNP), respectively. The same parameters were determined in 13 control subjects at baseline conditions and during a hyperinsulinemic-euglycemic glucose clamp. Baseline forearm blood flow (4.89 +/- 0.86 vs. 3.65 +/- 0.59 ml x (100 ml tissue)(-1) x min(-1)) and NO2- + NO3- concentration (30 +/- 8 vs. 24 +/- 3 micromol/l) were higher in type 1 diabetic patients than in control subjects (P < 0.05). Insulin infusion was associated with lower forearm blood flow and plasma (NO2- + NO3-) concentration (P < 0.05), irrespective of the prevailing glucose levels, as compared with patients under ketotic conditions. The responses to L-NMMA were significantly lower in type 1 diabetic patients during euglycemia and hyperglycemic hyperinsulinemia (-11 +/- 5 and -10 +/- 4%, respectively, of the ratio of the infused arm to the control arm) than in control subjects at baseline (-18 +/- 6%, P < 0.05) and during hyperinsulinemia (-32 +/- 11%, P < 0.01). We conclude that the acute loss of metabolic control is associated with a functional disturbance of the endothelial function characterized by hyperemia and increased NO release during ketosis and blunted NO-mediated vasodilatory response during restoration of metabolic control by intravenous insulin. This functional alteration is unlikely to be explained by hyperglycemia itself.

Acute Disease↗

Plasma nitrite reserve and endothelial function in the human forearm circulation.

Attenuation of endothelium-derived nitric oxide (NO) synthesis is a hallmark of endothelial dysfunction. Early detection of this disorder may have therapeutic and prognostic implications. Plasma nitrite mirrors acute and chronic changes in endothelial NO-synthase activity. We hypothesized that local plasma nitrite concentration increases during reactive hyperemia of the forearm, reflecting endothelial function. In healthy subjects (n = 11) plasma nitrite and nitrate were determined at baseline and during reactive hyperemia of the forearm using reductive gas-phase chemiluminescence and flow-injection analysis, respectively. Endothelium-dependent dilation of the brachial artery was measured as flow-mediated dilation (FMD) using high-resolution ultrasound. Results were compared to patients with endothelial dysfunction as defined by reduced FMD (n = 11). Reactive hyperemia of the forearm increased local plasma nitrite concentration from 68 +/- 5 to 126 +/- 13 nmol/L (p < 0.01), whereas in endothelial dysfunction nitrite remained unaffected (116 +/- 12 to 104 +/- 10 nmol/L; n.s.), corresponding to nitrite reserves of 94 +/- 21 and -8 +/- 4%. This was accompanied by a significantly greater increase in brachial artery diameter (FMD: 8.5 +/- 0.4% vs 2.9 +/- 0.5%, for healthy subjects and endothelial dysfunction, respectively; p < 0.001). This observation suggests that nitrite changes reflect endothelial function. Assessment of local plasma nitrite during reactive hyperemia may open new avenues in the diagnosis of vascular function.

Adult↗

Association of increased body mass index and impaired endothelial function among Hispanic women.

We tested the hypothesis that an increased body mass index was similarly associated with impaired endothelial function as measured by flow-mediated dilation in a high-risk, Hispanic population of men and women living in northern Manhattan. The association of flow-mediated dilation and body mass index was significant in women (beta -0.16 +/- 0.04, p <0.0001) but not in men (beta -0.02 +/- 0.06, p = 0.72). This is the first study to demonstrate a gender-specific difference in endothelial function associated with body mass index.

Age Factors↗

Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study.

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4+/-3.2 versus 7.4+/-2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5+/-0.3 versus 1.2+/-0.3 micromol.L(-1)), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.

Adult↗

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients.

The majority of patients undergoing solid organ transplantation develop hypertension, to which vasoconstriction and impaired endothelial function have been suggested to contribute. We compared basal vascular resistance and nitric oxide-mediated endothelial-dependent and independent vasoreactivity between cyclosporine-treated lung transplant recipients and healthy subjects. Forearm blood flow was measured by venous occlusion plethysmography at rest and during acetylcholine, glyceryltrinitrate and N(G)-monomethyl-L-arginine acetate (L-NMMA) infusion in 11 lung transplant recipients 3-5 years after transplantation and in eight healthy subjects. Forearm vascular resistance (FVR) was calculated. Plasma levels of endothelin-1 (ET-1) and von Willebrand factor (vWf) were analysed. Basal vascular resistance was 40% lower in transplant recipients than in healthy subjects (P = 0.021). Endothelial-dependent and independent vasodilation did not differ. Plasma levels of ET-1 and vWf were higher in transplant recipients (P = 0.009 and P < 0.001 respectively). There was a significant correlation between ET-1 levels and FVR in healthy subjects (r = 0.83, P = 0.042), but not in transplant recipients (r = -0.14, P = 0.70). The findings oppose the theory of generalized vasoconstriction and impaired endothelial function in the pathogenesis of hypertension after transplantation. Increased plasma levels of ET-1 do not cause increased FVR in lung transplant recipients.

Adult↗

Racial difference in endothelial function: role of the infective burden.

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.

Adult↗

Pioglitazone-induced insulin sensitization improves vascular endothelial function in nondiabetic patients with essential hypertension.

BACKGROUND: It has been suggested that insulin resistance is involved in the impaired vascular endothelial function not only in diabetic patients but also in hypertensive patients. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse endothelial dysfunction in hypertensive subjects. METHODS: Fifteen nondiabetic patients with essential hypertension were enrolled in this study. An oral glucose tolerance test (OGTT) and insulin sensitivity test were performed. Insulin sensitivity was determined with the steady-state plasma glucose (SSPG) method. Only subjects with insulin resistance (SSPG > or =8.3 mmol/L) were included. Endothelium-dependent vasodilation during reactive hyperemia (flow-mediated dilation) was evaluated using ultrasonography. Six months after treatment with the insulin-sensitizing agent pioglitazone (30 mg/day), these examinations were repeated in all subjects. RESULTS: Pioglitazone did not decrease fasting plasma glucose and hemoglobin A1c (HbA1c) in the nondiabetic subjects, although the area under the curve for glucose and insulin on OGTT significantly decreased. A marked decrease in SSPG was observed after pioglitazone treatment (10.7 +/- 1.4 to 7.9 +/- 2.1 mmol/L, P < .001). Endothelium-dependent vasodilation evaluated by flow-mediated dilation was also improved by pioglitazone (5.0% +/- 2.2% to 6.3% +/- 2.4%, P = .023). Furthermore, the increase in flow-mediated dilation was closely correlated with the decrease in SSPG (r = 0.72, P = .002) but not with the decrease in area under the curve for glucose or insulin on OGTT. Endothelium-independent dilation induced by glyceryl trinitrate was not altered by pioglitazone. CONCLUSIONS: The present findings demonstrate that pioglitazone improves endothelial function in nondiabetic hypertensive individuals with insulin resistance, and that the improvement is associated with the amelioration of insulin resistance itself rather than that of hyperglycemia or hyperinsulinemia.

Aged↗

Heterogeneity of endothelial function within the circulation.

As our understanding of endothelial function continues to evolve, it has become increasingly clear that the peripheral vasculature exhibits striking regional and segmental heterogeneity in the influence of the endothelial cell layer on vascular tone. This heterogeneity encompasses not only the normal interactions between endothelium-derived factors and vascular smooth muscle, but also the way in which these interactions can change during juvenile growth or in disease states such as hypertension. The underlying causes of this heterogeneity are multifactorial and include intrinsic differences among endothelial cell populations and differences in the endothelial cell microenvironment.

Animals↗

Endothelial function: a critical determinant in atherosclerosis?

Common conditions predisposing to atherosclerosis, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with endothelial dysfunction. Endothelial function has largely been assessed as endothelium-dependent vasomotion, at least in part based on the assumption that impaired endothelium-dependent vasodilation also reflects the alteration of other important functions of the endothelium. An important rationale for this approach has been the observation that endothelium-derived nitric oxide (NO), a major mediator of endothelium-dependent vasodilation, has important anti-inflammatory and antithrombotic properties, ie, inhibiting leukocyte adhesion, limiting platelet adhesion and aggregation, and the expression of plasminogen activator inhibitor-1 (PAI-1), a prothrombotic protein. Accumulating data suggest that the degree of impairment of endothelium-dependent vasomotion has profound and independent prognostic implications. A common mechanism underlying endothelial dysfunction relates to increased vascular production of reactive oxygen species. Recent studies also suggest that inflammation per se and C-reactive protein in particular may directly contribute to endothelial dysfunction. These findings raise the question of whether assessment of endothelial function can be used in the clinical setting to identify patients at high risk. New insights into mechanisms of endothelial dysfunction, such as a better understanding of the regulation of important vascular sources of oxygen radicals, may lead to novel therapeutic strategies with the potential to improve prognosis.

Animals↗

Methodological issues in the assessment of skin microvascular endothelial function in humans.

The study of microvascular function can be performed in humans using laser Doppler flowmetry of the skin. This technology lends itself to a wide range of applications for studying the endothelial function of skin blood vessels. We review the advantages and limitations of postocclusive hyperemia, local thermal hyperemia, acetylcholine iontophoresis, flowmotion and association with microdialysis as tools with which to investigate skin microvascular endothelial function in humans. Postocclusive hyperemia, thermal hyperemia and acetylcholine iontophoresis provide integrated indexes of microvascular function rather than specific endothelial markers. However, they are valuable tools and can be used as surrogate endpoints in clinical trials in which the assessment of microvascular function in humans is required.

Acetylcholine↗

Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease.

Aerobic exercise training improves endothelial vasomotor function in the coronary circulation of patients with coronary artery disease (CAD), an effect that has been attributed to local repetitive increases in shear stress on the endothelium. To study the effects of exercise on endothelial function in the peripheral circulation, we used vascular ultrasound to examine flow-mediated dilation and nitroglycerin-mediated dilation in the brachial and posterior tibial arteries of 58 subjects with CAD. Studies were performed at baseline and after 10 weeks in 40 subjects (aged 59 +/- 10 years) who participated in a supervised cardiac rehabilitation program that predominantly involved moderate intensity leg exercise (three 30-minute sessions/week), and 18 matched patients who did not exercise and maintained a sedentary lifestyle. Exercise was associated with a 29% increase in functional capacity (7.3 +/- 2.2 vs 9.4 +/- 2.7 METs, p <0.001), and significant improvement in endothelium-dependent, flow-mediated dilation in a conduit artery of the leg, but not the arm. Nitroglycerin-mediated dilation in the upper arm and lower extremity was unaffected. These findings suggest that exercise improves endothelial function in peripheral conduit arteries of patients with CAD and that the beneficial effect may be more marked in the vascular beds of the exercised limbs.

Arm↗

A rapid and reproducible on line automated technique to determine endothelial function.

OBJECTIVE: To evaluate clinically a new on line, automated technique to measure flow mediated dilatation (FMD) as a marker of endothelial function. DESIGN: Prospective study. PATIENTS: 12 healthy volunteers and 12 patients with significant, angiographically documented coronary artery disease. INTERVENTIONS: Brachial arteries were imaged using a standard vascular ultrasound system with a 5-12 MHz linear transducer. Arterial diameter was measured on line (in real time) by connecting the ultrasound system to a personal computer equipped with a frame grabber and artery wall detection software (VIA) specially developed by the authors' group. By using this new technique, FMD was measured following 4.5 minutes of ischaemia of the proximal forearm in all subjects on two separate days. RESULTS: The mean (SD) day to day variability in FMD measurements was 0.90 (0.48)%,which compares very favourably with current methods. The FMD measurement was available within seconds of completing the scan. CONCLUSIONS: Personal computer based automated techniques to assess FMD involve image acquisition and recording after which a second (off line) image interpretation session is required. The need for off line analysis makes current methods time consuming and increases the variability of measurement. This on line, automated analysis technique for FMD assessment reduces the variability and greatly increases the speed of measurement. Using this system may mean that fewer patients will be required in clinical trials assessing the effects of interventions on endothelial function. Adopting this method may also facilitate the screening of larger numbers of subjects for endothelial dysfunction.

Adult↗

Impaired microvascular reactivity and endothelial function in patients with Cushing's syndrome: influence of arterial hypertension.

The aim of the study was to evaluate skin microvascular reactivity (MVR) and possible influencing factors (fibrinolysis, oxidative stress, and endothelial function) in patients with Cushing's syndrome. Twenty-nine patients with active Cushing's syndrome (ten of them also examined after a successful operation) and 16 control subjects were studied. Skin MVR was measured by laser Doppler flowmetry during post-occlusive (PORH) and thermal hyperemia (TH). Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its inhibitor (PAI-1). N-acetyl-beta-glucosaminidase, E-selectin, P-selectin, and ICAM-1 were used as markers of endothelial function. Oxidative stress and endothelial dysfunction was present in patients with hypercortisolism, however, increased concentration of ICAM-1 was also found in patients after the operation as compared to controls (290.8+/-74.2 vs. 210.9+/-56.3 ng.ml(-1), p<0.05). Maximal perfusion was significantly lower in patients with arterial hypertension during PORH and TH (36.3+/-13.0 vs. 63.3+/-32.4 PU, p<0.01, and 90.4+/-36.6 vs. 159.2+/-95.3 PU, p<0.05, respectively) and similarly the velocity of perfusion increase during PORH and TH was lower (3.2+/-1.5 vs. 5.2+/-3.4 PU.s(-1), p<0.05, and 0.95+/-0.6 vs. 1.8+/-1.1 PU.s(-1), p<0.05, respectively). The most pronounced impairment of microvascular reactivity was present in patients with combination of arterial hypertension and diabetes mellitus.

Adult↗