The effect of revascularization of atherosclerotic renal artery stenosis on coronary flow reserve and peripheral endothelial function.

BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are at increased risk of heart disease because of associated hypertension, coronary artery disease, cardiac failure and chronic kidney disease. Although suggested to be beneficial, the cardiac effects of renal artery revascularization have not been well characterized. Our aim was to analyze the effects of percutaneous dilatation of renal artery stenosis (RAS) in ARVD patients on coronary and peripheral vascular function. METHODS: Nineteen ARVD patients [11 females and 8 males, age at study entry (mean ± SD) 69 ± 10 years] were treated by dilatation of unilateral (n = 9) or bilateral (n = 10) RAS, mainly because of uncontrolled or refractory hypertension. The patients were studied before and after the procedure (103 ± 29 days). They underwent echocardiography and peripheral artery endothelial function testing using flow-mediated dilatation (FMD) of brachial artery at rest and during reactive hyperemia. Myocardial blood flow was measured using quantitative PET perfusion imaging at baseline and during dipyridamole-induced hyperemia. RESULTS: Peripheral endothelial function, tested by FMD, as well as systolic blood pressure and left ventricular mass were improved in patients with bilateral RAS. However, myocardial perfusion and coronary flow reserve (CFR) did not change after the RAS dilatation. CONCLUSION: This is the first study to analyze the stage of myocardial perfusion and CFR in ARVD patients. Although peripheral endothelial function, systolic blood pressure and left ventricular hypertrophy were improved in patients with bilateral RAS by revascularization of RAS, it did not have any effect on coronary perfusion.

¿Cuál es el momento idóneo para la medición por ultrasonidos de la dilatación braquial mediada por flujo? / What is the ideal moment for ultrasound measurement of brachial artery flow-mediated dilation?

Introducción y objetivo. Las guías técnicas de medición de la dilatación braquial mediada por flujo (DBMF) recomiendan su medida en diástole para evitar la influencia de la distensibilidad (complianza) arterial en los resultados. Sin embargo, no existen estudios que corroboren esta hipótesis, por lo que éste es el objetivo primordial de nuestro trabajo. Sujetos y métodos. Se reclutaron dos grupos de sujetos con estos criterios: grupo I, sujetos sanos con índice tobillo/brazo (ITB) > 0,9 y menores de 30 años, y grupo II, pacientes con arteriopatía periférica sintomática definida por un ITB < 0,9. Se les realizó la medición de la dilatación de la arteria braquial mediada por flujo (DBMF) en el brazo derecho en sístole (S) y diástole (D). Se midió en el mismo acto el ITB y se recogieron los factores de riesgo y los tratamientos. Además, se determinó la dilatación mediada por flujo en ambas arterias femorales (DFMF). Resultados. Se reclutaron 36 y 33 sujetos de los grupos I y II, respectivamente. Se compararon los valores de dilatación en S y D y se representaron como grupo: S / D (valor p). DBMF: I + II: 8,1 ± 4,6% / 7,6 ± 4,9% (p = 0,3); I: 10,8 ± 2,9% / 9,9 ± 3,8% (p = 0,055); II: 5,2 ± 4,3% / 5,16 ± 4,8% (p = 0,3). DFMF: I + II: 3,13 ± 3,6% / 2,8 ± 3,6% (p = 0,35); I: 5,3 ± 2,9% / 4,8 ± 2,6% (p = 0,02); II: 0,6 ± 2,5% / 0,6 ± 3,4% (p = 0,9). Conclusiones. Si se asume la influencia de la complianza en la dilatación arterial, se observa que la dilatación mediada por flujo en sístole es superior a la diastólica en los sujetos sanos, mientras que en los enfermos esta diferencia es prácticamente inexistente. Aunque la diferencia en la arteria braquial de sujetos sanos no llega a la significación (p = 0,055), sí que lo hace en la femoral (p = 0,02), por lo que, al valorar los datos en conjunto, recomendamos utilizar la medición en diástole para evitar sesgos a la hora de realizar comparaciones entre sanos y enfermos

Introduction and aims. The technical guides to measuring the brachial artery flow-mediated dilation (BFMD) recommend that it should be measured in the diastolic phase in order to prevent results from being influenced by arterial distensibility (compliance). No studies have been conducted, however, to confirm this hypothesis and this is therefore the main purpose of our research. Subjects and methods. Two groups of subjects were recruited on the basis of the following criteria: group I, healthy subjects with an ankle-brachial index (ABI) > 0.9 and below 30 years of age, and group II, composed of patients with symptomatic peripheral arterial disease that was defined by an ABI < 0.9. Brachial artery flow-mediated dilation was measured in the right arm in both the systolic (S) and diastolic (D) phases. The ABI was measured at the same time and the risk factors and treatments were collected. Flow-mediated dilation was also determined in both femoral arteries (FFMD). Results. Groups I and II consisted of 36 and 33 subjects respectively. The dilation values in the S and D phases were compared and represented as a group: S / D (value p). BFMD: I + II: 8.1 ± 4.6% / 7.6 ± 4.9% (p = 0.3); I: 10.8 ± 2.9% / 9.9 ± 3.8% (p = 0.055); II: 5.2 ± 4.3% / 5.16 ± 4.8% (p = 0.3). FFMD: I + II: 3.13 ± 3.6% / 2.8 ± 3.6% (p = 0.35); I: 5.3 ± 2.9% / 4.8 ± 2.6% (p = 0.02); II: 0.6 ± 2.5% / 0.6 ± 3.4% (p = 0.9). Conclusions. If it is assumed that compliance influences arterial dilation, systolic flow-mediated dilation is seen to be higher than in the diastolic phase in healthy subjects, whereas this difference is practically inexistent in patients. Although the difference in the brachial artery of healthy subjects does not reach significance (p = 0.055), it does in the femoral artery (p = 0.02). Therefore, on appraising the data as a whole, we recommend measurement in the diastolic phase in order to avoid the occurrence of biases when comparing between healthy and sick subject

Vacuole formation in the endothelium of rat extremity vessels depends on fixation techniques and vessel type.

Applying immersion fixation for electron microscopy, huge clear endothelial membrane-bound vacuoles of 0.1-3 microm diameter were noted in the extremity veins of Sprague-Dawley rats. Histological and electron microscopic histochemical methods were applied to determine whether they were the product of programmed cell death or any other kind of cell damage. Image analyzer was used to measure the total area of the vacuoles in the endothelium cells. Neither lipid content nor acidic phosphatase activity could be identified in the vacuoles. In saphenous and brachial veins, the vacuoles occupied 20.6 +/- 2.21% and 18 +/- 2.45% of the endothelium, respectively. Venous endothelium of two different strains of rat also contained the vacuoles. No such structures appeared in extremity arteries. Long-term tilting did not influence vacuolization. Using in vivo whole body fixation, only pinocytotic and dense microvesicles, but no vacuoles were noted. In conclusion, the clear vacuolar structures represent neither lipid inclusions nor secondary lysosomes. The method of tissue fixation is critical when venous endothelial vesicles are investigated. It is presumed that the vacuoles originated from intra- or intercellular microstructures, and that in case of the collapsible vein segments, their size is increased under the pathological-hypoxic and low-pressure-conditions of in vitro fixation.

Diagnóstico preclínico de la aterosclerosis: función endotelial / Preclinical diagnosis of arteriosclerosis: endothelial function

Se hace una revisión de la técnica para medir, de manera incruenta, la función del endotelio vascular en la arteria braquial humana. Se revisan los principales estudios donde se ha empleado esta técnica haciendo énfasis en su relación con la aterosclerosis de las arterias coronarias. Por último, se hace un recuento de sus limitaciones y posibilidades(AU)

An incremental test to identify the pain threshold speed in patients with intermittent claudication.

The purpose of this study was to develop a test for identifying the speed of onset of claudication, or pain threshold speed (PTS), in 16 patients affected by intermittent claudication. An echo-Doppler examination and the ankle-brachial index (ABI) determination were also performed. Test repeatability was evaluated in 10 patients retested within a few days. All 16 patients underwent the incremental walking test 3 times during a 6-month rehabilitation training program to verify the test's sensitivity in detecting the expected functional modifications. PTS was identified in all patients examined and the test-retest correlation coefficient (R) for PTS was 0.98. During the 6-month rehabilitation period, the ABI rose from 0.43 +/-0.16 to 0.72+/-0.15 for the worst limb and PTS also rose significantly from 3.9+/-1.4 km/h to 6.1+/-1.1 km/h. The average increments of ABI and PTS were significantly correlated. An incremental walking test for the identification of the walking speed at which claudication occurs has been developed. The PTS is a reproducible parameter that can be combined with other test results to establish the severity of the disease and to check any modifications that occur during rehabilitation.

The effects of mental stress and the cold pressure test on flow-mediated vasodilation.

As a stressful lifestyle has been associated with coronary heart disease, this study aim to evaluate how two stressful tests influence endothelial-dependent vasodilation evaluated by flow-mediated dilation (FMD) of the brachial artery. FMD following 5 min of occlusion of the forearm was evaluated in young healthy volunteers with measurements of brachial artery diameter and blood flow (BABF) using ultrasound before and during a mental arithmetic task (MAT), and during cold pressure test (COP). MAT and COP increased blood pressure to a similar degree (18-21 mmHg). The COP induced a significant reduction in FMD compared to the baseline levels (from 9.3 +/- 3.9 to 5.9 +/- 3.2%, p < 0.01), as well as to the MAT, which in itself did not influence FMD (10.1 +/- 5.0%). However, as MAT increased BABF during hyperaemia significantly, the FMD to BABF ratio was significantly reduced by both stress tests (p < 0.05). Time-control experiments showed FMD measurements to be reproducible and that MAT and COP by themselves only marginally affected brachial artery diameter. In conclusion, cold pressure stress induced an impairment in FMD, but no effect was induced by a MAT. However, when FMD was normalized for the degree of hyperaemic blood flow, the driver of the vasodilation in the brachial artery, a reduction in flow-mediated vasodilation was seen during both mental and cold pressure stress.

Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress.

AIMS: it appears that hypertriglyceridemia (HTG) is a risk factor of atherosclerosis as demonstrated by recent studies. In this study, we analyzed the effects of acute HTG on endothelial function and oxidative stress, which are important mechanisms in the pathogenesis of atherosclerosis. METHODS AND RESULTS: in a high fat meal group (n = 11), serum triglycerides and PMA-activated leukocyte O(2)(-)* production were significantly (P < 0.005) increased from 146 +/- 69 mg/dl and 4.09 +/- 0.93 nmol/10(6) cells/min preprandially to 198 +/- 88 mg/dl and 5.49 +/- 1.19 nmol/10(6) cells/min, respectively, 2 h after eating a high-fat meal. The flow-mediated endothelium-dependent brachial artery dilation (FMD; high-resolution ultrasound) was decreased from 13.7 +/- 3.3% preprandially to 8.2 +/- 3.7%, 2 h after eating a high-fat meal (P < 0.005). However, following a low-fat meal (n = 9), there were no significant changes in triglycerides, leukocyte O(2)(-)* production and FMD. Changes of serum triglycerides were correlated negatively (r = -0.650, P < 0.005) with changes of FMD, but were correlated positively (r = 0.798, P < 0.001) with changes of leukocyte O(2)(-)* production, which - in turn - were correlated negatively (r = -0.784, P < 0.001) with changes of FMD in all study subjects (mean age: 56 years, n = 20). CONCLUSIONS: this study suggests that acute HTG causes endothelial dysfunction via enhanced oxidant stress and this may pave the way for the development of atherosclerosis under chronic conditions.

Influence of long-term head-down body position on innervation density in extremity blood vessels.

The aim of the present study was to quantitate and compare the density of nerve terminals (NTD), as well as of their synaptic vesicle population (SyVD) in saphenous and brachial vein and artery, obtained from rats maintained in the horizontal or head-down tilted (HDT) position for two weeks. The same technique was applied as that for the head-up tilt study.

Corrosion cast of the vascularization of Mugil Cephalus gills.

The spatial organization of the microcirculation in gills of Mugil Cephalus, was examined by scanning electron microscopic analysis of corrosion cast prepared by intravascular injection of methyl methacrylate. The afferent branchial artery originates from the ventral aorta and gives rise to afferent filamental artery. From the medio-lateral wall of the afferent filamental artery, afferent lamellar arterioles originate which supply one or more lamellae. The lamellar efferent arterioles, which drain the blood coming from the lamellae into the efferent filamental arteries, continue with the efferent branchial arteries and then the dorsal aorta. The techniques used so permitted to evaluate the structure and the interrelationships of the vascular pathways, explaining the regulation and the distribution of the blood flow in the gills.

Ultrastructural changes in a case of mucoid degeneration of the brachial artery.

An electron microscopic (EM) description of mucoid degeneration of the brachial artery in a 67 year old man is presented. In this case, the affected artery showed mucoid degeneration of the intima and media circumferentially, dissecting and destroying the muscle fibres. Ultrastructurally, mucoid degenerating muscle cells showed numerous large mucin-containing vesicles in the cytoplasm. Cells were widely separated by large accumulation of mucoid material, which appeared to penetrate the extracellular collagen fibre bundles. Most of the nuclei of the smooth muscle cells displayed typical necrotic changes undergoing dissolution or having already broken up into discrete fragments. This case of intimo-medial degeneration (IMMD) suggests that the condition could arise spontaneously anywhere in the inner coats of the arterial system away from the vessels that are close to synovial joints. This is a rare presentation of IMMD of arteries, which has been described mainly in the aorta and its major branches.

The anatomy, ultrastructure and fluid dynamics of the developing vasculature of the embryonic chick wing bud.

The spatiotemporal sequence of vascular pattern development in the embryonic chick wing bud and surrounding shoulder, flank and belly regions is detailed for Hamburger-Hamilton (1951) stages 20-25. Vasculature was microinjected with an unreactive aqueous tracer (aniline blue), and major traffic patterns were visualized. Formation of extensive avascular regions and the emergence of chondrogenic phenotypes are correlated with the retreat of the vasculature from the wing core. Ultrastructural studies of vascular cells show that vessels remain monolayered and undifferentiated until stage 25, after the adult vascular pattern has been laid down. Vascular cytodifferentiation occurs only in the cells of the brachial artery until stage 35, with the veins and capillaries retaining an 'early' morphology. This vascular pattern may be an important component reflecting or directing limb pattern development.

A light and electron microscopic study on the embryonic development of the rat carotid body.

The embryonic development of the rat carotid body was studied with electron microscopy. In the 11 mm embryo a cell aggregation consisting of undifferentiated cells and unmyelinated nerve fibers appears on the anterior wall of the third branchial artery. Granule-containing cells appear in the 12 mm embryo and continue to increase in number as the cellular aggregation increases in size and becomes separated from the wall of the third branchial artery. Synapse formation and the appearance of fenestrated capillaries occur almost simultaneously at the 17 mm stage. There are two types of synapses, one with membrane densification and vesicles clustered inside the nerve endings, the other with dense material and vesicles inside the granule-containing cells. At the 20 mm stage the undifferentiated cells send enveloping cytoplasmic processes toward adjacent granule-containing cells and the carotid body anlage displays rudimentary lobules.

Venous atherosclerosis associated with arteriovenous fistulas for hemodialysis.

In two patients, venous loops fashioned into arteriovenous anastomoses for long-term hemodialysis developed gross irregularity and narrowing of the lumen. Histological and ultrastructural examination of the affected vein in one patient revealed atherosclerosis similar to that that develops in the anastomosed veins of experimental arteriovenous fistulas in sheep. The second patient, with angiographically similar changes in the venous loop, developed on aneurysm followed by thrombotic occlusion of the arteriovenous fistula. The development of venous atherosclerosis in these patients was analogous to that in the experimental animal, and was attributed to local hemodynamic stresses in the vein associated with the shunt.