A young man with intimomedial mucoid degeneration of the brachial artery.

Intimomedial mucoid degeneration is a rare disorder and has been described as a distinctly different entity from Erdheim's cystic medial necrosis. Most studies show a strong predominance in African American females with hypertension. In our case report, we describe the presence of a large brachial aneurysm in a young white male with intimomedial mucoid degeneration.

Venous blood gas and metabolite response to low-intensity muscle contractions with external limb compression.

The effect of low-intensity resistance exercise with external limb compression (100 [EC100] and 160 [EC160] mm Hg) on limb blood flow and venous blood gas-metabolite response was investigated and compared with that of high-intensity resistance exercise (no external compression). Unilateral elbow flexion muscle contractions were performed at 20% (75 repetitions, 4 sets, 30-second rest intervals) and 70% of 1-repetition maximum (1-RM; 3 sets, each set was until failure, 3-minute rest intervals). Precontraction brachial arterial blood flow (Doppler ultrasound) was reduced with EC100 or EC160 (56% and 39% of baseline value, respectively) compared with no external compression (control). At 20% 1-RM, brachial arterial blood flow increased after contractions performed with EC160 (190%), but not with the others. Decreases in venous oxygen partial pressure (P(v)O(2)) and venous oxygen saturation (S(v)O(2)) were greater during EC100 and EC160 than control (mean [SE]: P(v)O(2), 28 [3] vs 26 [2] vs 33 [2] mm Hg; S(v)O(2), 41% [5%] vs 34% [4%] vs 52% [5%], respectively). Changes in venous pH (pH(v)), venous carbon dioxide partial pressure (P(v)CO(2)), and venous lactate concentration ([L(-)](v)) were greater with EC160 than EC100 and/or control (pH(v), 7.19 [0.01] vs 7.25 [0.01] vs 7.27 [0.02]; P(v)CO(2), 72 [3] vs 64 [2] vs 60 [3] mm Hg; [L(-)](v), 5.4 [0.6] vs 3.7 [0.4] vs 3.0 [0.4] mmol/L, respectively). Seventy percent 1-RM contractions resulted in greater changes in pH(v) (7.14 [0.02]), P(v)CO(2) (91 [5] mm Hg), and [L(-)](v) (7.0 [0.5] mmol/L) than EC100 and EC160, but P(v)O(2) (30 [4] mm Hg) and S(v)O(2) (40% [3%]) were similar. In conclusion, changes in pH(v), P(v)CO(2), and [L(-)](v), but not in P(v)O(2) and S(v)O(2), are sensitive to changes in relative, "internal" intensity of low-intensity muscle contractions caused by reduced blood flow (EC160) or high-intensity muscle contractions. Given the magnitude of the changes in pH(v), P(v)CO(2), and [L(-)](v), it appears plausible that they may be involved in stimulating the observed increase in muscle activation via group III and IV afferents.

Protein expression in vascular endothelial cells obtained from human peripheral arteries and veins.

Studying molecular mechanisms of vascular endothelial function in humans is difficult in part because of limited access to arteries. Access to peripheral veins is more practical. We determined if differences in protein expression of endothelial cells (EC) collected from a peripheral artery are reflected in measurements made on EC obtained from peripheral veins. EC were collected from the brachial artery and an antecubital vein of 106 healthy adults (60 men and 46 women, age 18-77 years). Quantitative immunofluorescence was used to measure protein expression of endothelial nitric oxide synthase (eNOS), Ser-1177 phosphorylated eNOS, manganese superoxide dismutase, nitrotyrosine, xanthine oxidase and nuclear factor-kappaB p65. Protein expression in EC obtained from brachial artery and antecubital vein sampling was moderately to strongly related (r = 0.59-0.81, all p < 0.0001, mean r = 0.70). Moreover, differences between subgroups in the lowest and highest tertiles of protein expression in EC obtained from arterial samples were consistently reflected in EC obtained from venous collections. These findings indicate that interindividual and group differences in expression of several proteins involved in nitric oxide production, oxidant production, antioxidant defense and inflammatory signaling in EC obtained from brachial artery sampling are consistently reflected in EC obtained from venous samples. Thus, EC collected from peripheral veins may provide a useful surrogate for EC obtained from arteries for measurements of EC protein expression in humans.

Utility and barriers to performance of the ankle-brachial index in primary care practice.

Peripheral arterial disease is prevalent, associated with increased cardiovascular morbidity and mortality, and is underdiagnosed. Nevertheless, systematic efforts to provide early office-based peripheral arterial disease detection are not routinely implemented in office practice. The PARTNERS Program implemented the ankle-brachial index (ABI) measurement in primary care outpatient clinics in order to model practical dissemination of this technique and thus improve office-based peripheral arterial disease detection. The objective of this study was to identify clinician-defined factors that were perceived to foster acceptance of, or create barriers to, the use of the ABI in office practice. The ABI Utilization Survey was administered to primary care clinicians who participated in the PARTNERS Program, as well as to additional primary care clinicians who participated in the PARTNERS Preceptorship. The survey assessed six parameters: pre- and post-participation office ABI utilization; perceived clinical utility of the ABI; perceived value of the ABI data relative to other commonly used office disease detection methods; feasibility of implementing office-based ABI testing; definition of factors limiting utilization of the ABI in office practice; and the role of office staff in performing the ABI test. Survey data were obtained from 886 respondents. A total of 68% of respondents did not measure the ABI prior to participation in the PARTNERS Program. After Program participation, the frequency of office ABI use increased from 12% to 43% weekly and 13% to 39% monthly. The few participants who reported using the ABI only once a year (annually) did not significantly change after the program. Most clinicians believed that the ABI was useful in the diagnosis and management of both symptomatic (96%) and asymptomatic (89%) peripheral arterial disease. Moderate to major barriers to use of the ABI included time constraints (56%), lack of reimbursement (45%), and staff availability (45%). Nearly all (88%) clinicians believed that it was feasible to incorporate ABI into daily practice. Overall, most clinicians (57-75%) believed that ABI was equal to, or more useful, than other widely available and reimbursed screening tests in preserving their patients' health. In conclusion, the ABI was perceived by primary care clinicians to be a clinically useful diagnostic test. Limited reimbursement and time were identified as the primary barriers to its widespread use. Once learned, most clinicians stated that the ABI would continue to be frequently used in their office practice. The ABI is a simple peripheral arterial disease detection tool that can be successfully applied in primary care office practices.

Extrahepatic synthesis of factor VII in human atherosclerotic vessels.

OBJECTIVE: Coagulation is initiated by the interaction of tissue factor (TF) with plasma coagulation factors VII (FVII) and X (FX). TF is highly expressed in atherosclerotic lesions, but little is known about the synthesis of FX or FVII outside of the liver. Previous studies suggested that macrophages synthesize FVII. We therefore hypothesized that macrophages within atherosclerotic lesions may produce FVII, leading to partial activation of the coagulation cascade. METHODS AND RESULTS: Immunohistochemistry was performed using antibodies against FVII, FX, and TF on normal and atherosclerotic vessels. In atherosclerotic lesions, FVII immunostaining was colocalized with TF in macrophages and spindle-shaped smooth muscle cells. FVII mRNA was also detected in these cells using in situ hybridization, suggesting the local synthesis of FVII in atherosclerosis. Reverse transcriptase-polymerase chain reaction confirmed the presence of FVII mRNA in normal and atherosclerotic vessels as well as smooth muscle cells, fibroblasts, and keratinocytes in vitro. CONCLUSIONS: The localization of FVII synthesis outside the liver may be indicative of other cellular functions for this coagulation protein. The observed coexpression of TF and FVII may contribute to autocrine signaling via thrombin-independent mechanisms and may represent a novel mechanism contributing to growth in the setting of vascular disease.

Short- and long-term changes of flow-mediated vasodilation in patients under statin therapy.

BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been shown to improve in response to lipid-lowering therapy and other therapeutic interventions, usually within 1 to 2 months. Whether FMD remains improved under therapy in the longer term is unknown. HYPOTHESIS: The aim of this study was to examine the short- and long-term changes of FMD under statin therapy. METHODS: Flow-mediated vasodilation and nitroglycerin-mediated vasodilation (NMD) of the BA were measured with high-resolution ultrasound (13 MHz) at baseline and at 4 and 10 months in 18 consecutively recruited patients with coronary artery disease (CAD), in whom statin therapy was newly established. RESULTS: The decrease of total plasma cholesterol levels after 4 and 10 months of statin therapy (243 +/- 31 vs. 186 +/- 30 vs. 191 +/- 40 mg/dl; p < 0.001) was accompanied by an increase in FMD from 4.4 +/- 3.8% at baseline to 9.6 +/- 2.7% at 4 months and to 9.5 +/- 2.6% at 10 months (p < 0.001). Nitroglycerin-mediated vasodilation showed a trend toward improvement after 4 months (14.6 +/- 7.5 vs. 19.1 +/- 3.6 vs. 19.4 +/- 5.6%; NS). The FMD/NMD ratio also rose significantly after 4 months and remained improved after 10 months of statin therapy (0.31 +/- 0.25 vs. 0.52 +/- 0.16 vs. 0.50 +/- 0.14; p < 0.01). CONCLUSION: Statin therapy is associated with sustained improvement of endothelial function up to 10 months. These data support the utility of FMD for the assessment of vascular function in response to lipid-lowering therapy or other therapeutic interventions in long-term studies.

Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress.

BACKGROUND: Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure. METHODS AND RESULTS: Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS). CONCLUSION: The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.

Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter.

BACKGROUND: Brachial artery ultrasound has been proposed as an inexpensive, accurate way to assess cardiovascular risk in populations. However, analysis and interpretation of these data are not uniform. METHODS: We analysed the relationship between relative and absolute changes in brachial artery diameter in response to flow-mediated dilation and age, gender and baseline diameter among 4,040 ultrasound examinations from subjects aged 14 to 98 years. RESULTS: Reproducibility studies demonstrated intra- and interreader and intrasubject correlations from 0.67 to 0.84 for repeated measures of per cent change in diameter. Per cent change in diameter after flow stimulus was 3.58 +/- 0.10% (mean +/- standard deviation). Corresponding values for baseline diameter and absolute change in diameter were 4.43 +/- 0.87 mm and 0.15 +/- 0.01 mm, respectively. Baseline diameter and its variance were inversely related to per cent change in diameter (P< 0.001). In contrast, absolute change in diameter was more uniform throughout the range of baseline diameters. Baseline diameter was directly related, and per cent change in diameter inversely related, to age (P < 0.001 for all three measures). Time to maximum vasodilator response increased with age (P < 0.001). Women (n=2,315) had significantly larger per cent change in diameter than men (n=1,725) (P < 0.001). However, after adjustment for age and baseline diameter, per cent and absolute change were 5% smaller in women than men (P < 0.05 for both). In multivariate analysis, age was overwhelmingly the most important determinant of absolute change in diameter (P < 0.001). CONCLUSIONS: Automated analysis of brachial flow-mediated vasodilator responses is both feasible and reproducible in large-scale clinical and population-based research.

Analysis of collagen type III by uninterrupted sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting: changes in collagen type III polymorphism in aging rats.

A new method of type III collagen analysis by uninterrupted sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with immunoblotting was developed. The electrophoresis was carried out with gels containing 4 M urea. A negatively charged reducing agent, thioglycolic acid, was added to the running buffer of the cathodic reservoir between 15 and 20 min after Bromphenol Blue (BPB) migrated to the top of the separating gel, to reduce interchain disulfide binding of the collagen. The polymorphic type III collagens, i.e., an alpha-chain derived from a trimer [alpha 1(III)]3 with interchain disulfide bonds but without covalent cross-links, alpha 1(III), a beta-chain with covalent cross-links, beta(III), or an alpha-chain released from a trimer without reduction of the disulfide bonds, alpha*1(III), were identified by immunostaining and quantified by densitometry. Using this method, changes in collagen type III polymorphism with aging were examined in the aorta, brachial artery, and skin of rats. The total quantity of collagen type III decreased with aging in all tissues. beta(III) was the major component in the aorta and brachial artery, but alpha 1(III) was the major component in the skin. With increasing age from 3 to 60 weeks, the ratio of beta(III) to alpha 1(III), which is correlated with the extent of covalent cross-linking, showed a steep increase in the aorta but only a slight increase in the skin and it remained almost constant in the brachial artery.(ABSTRACT TRUNCATED AT 250 WORDS)