Growing-Related Changes in Arterial Properties of Healthy Children, Adolescents, and Young Adults Nonexposed to Cardiovascular Risk Factors: Analysis of Gender-Related Differences.

The aims of our work were to determine normal aging rates for structural and functional arterial parameters in healthy children, adolescents, and young adults and to identify gender-related differences in these aging rates. Methods. 161 subjects (mean: 15 years (range: 4-28 years), 69 females) were studied. Subjects included had no congenital or chronic diseases, nor had they been previously exposed to traditional cardiovascular risk factors. Arterial parameters assessed were (1) central blood pressure (BP) and aortic pulse wave analysis, (2) arterial local (pressure-strain elastic modulus) and regional (pulse wave velocity, PWV) stiffness, and (3) arterial diameters and carotid intima-media thickness (CIMT). Simple linear regression models (age as the independent variable) were obtained for all the parameters and the resulting rates of change were compared between genders. Results. No gender-related differences were found in mean values of arterial structural and functional parameters in prepubertal ages (4-8 years), but they started to appear at ~15 years. Boys showed a greater rate of change for central systolic BP, central pulse pressure, CIMT, and carotid-femoral PWV. Conclusion. Gender-related differences in arterial characteristics of adults can be explained on the basis of different growing-related patterns between boys and girls, with no existing differences in prepubertal ages.

Carotid-radial pulse wave velocity as a discriminator of intrinsic wall alterations during evaluation of endothelial function by flow-mediated dilatation.

UNLABELLED: Flow-mediated dilatation (FMD) is the most accepted technique for the evaluation of endothelial function. However, it has been show a great inter-subject variability limiting its clinical use. Carotid-radial pulse wave velocity (PWVcr) was proposed as an alternative tool for the evaluation of endothelial function. At the present, there is no doubt that PWVcr reduces its values in response to reactive hyperemia test (RHT) in healthy subjects. AIMS: a) to determine simultaneously the temporal profile of FMD, PWVcr and shear rate in response to RHT and b) to describe and analyze how subjects "FMD responders" or "non-responders" behave regards to PWVcr changes. METHODS: 34 Healthy young subjects were included. The PWVcr (strain gauge mechanotransducers), brachial diameter (B-Mode ultrasound and blood flow velocity (Doppler ultrasound) were measured before (baseline) the cuff was inflated and after its deflation (5 minutes). 10(th) percentiles FMD and PWVcr changes in the population were used for the definition of the subjects ("responders and non-responders"). RESULTS: Changes in PWVcr, brachial arterial diameter and shear rate were evidenced after the cuff release (p<0.05). There were differences in the PWV and FMD temporal profiles. Within "FMD responders" there were "PWV responders and non-responders". CONCLUSION: Assessing RHT-related changes in PWVcr in the context of a FMD evaluation, could be useful as a discriminator of intrinsic wall alterations giving additional information of vascular dynamics.

Changes in wall viscosity and filtering as determinant of carotid and femoral atherosclerotic plaque vulnerability: theoretical analysis.

Atherosclerotic plaque complication is a major cause of vascular accidents. Although a variety of factors have been proposed as key factors in these process, the mechanism that contribute to this problem remain to be characterized. Previously we demonstrated that changes in arterial wall viscous and elastic properties and/or in the filtering function (FF) could be part of the arterial wall alterations basis. If these properties are altered in arteries with atherosclerotic plaques remains to be analyzed. Our aims were 1) to analyze the arterial wall visco-elasticity and FF of carotid and femoral segments with atherosclerotic plaques, 2) to compare them with the mechanical behavior of segments without plaques (from the same artery) and of healthy arteries studied non-invasively. To this end, in each arterial segment, pressure and diameter signals were obtained, in vitro (circulation mock) and in vivo (non-invasive recordings). In atherosclerotic arteries recordings were performed on plaques and near regions without plaques. In each segment, the elasticity, the viscosity, and the wall FF were quantified. Atherosclerotic vessels, and particularly plaque regions, showed a reduced viscosity and FF. At the light of our results, hypothetical links between plaque events and changes in visco-elasticity and FF were discussed.

Linear and nonlinear viscoelastic modeling of ovine aortic biomechanical properties under in vivo and ex vivo conditions.

This study uses linear and nonlinear viscoelastic models to describe the dynamic distention of the aorta induced by time-varying arterial blood pressure. We employ an inverse mathematical modeling approach on a four-parameter (linear) Kelvin viscoelastic model and two five-parameter nonlinear viscoelastic models (arctangent and sigmoid) to infer vascular biomechanical properties under in vivo and ex vivo experimental conditions in ten and eleven male Merino sheep, respectively. We used the Akaike Information Criterion (AIC) as a goodness-of-fit measure. Results show that under both experimental conditions, the nonlinear models generally outperform the linear Kelvin model, as judged by the AIC. Furthermore, the sigmoid nonlinear viscoelastic model consistently achieves the lowest AIC and also matches the zero-stress vessel radii measured ex vivo. Based on these observations, we conclude that the sigmoid nonlinear viscoelastic model best describes the biomechanical properties of ovine large arteries under both experimental conditions considered in this study.

Non-invasive assessment of atherosclerotic plaques effects on the segment-to-segment human carotid visco-elasticity and filtering.

Although a variety of factors have been proposed as key factors of the atherosclerotic plaque vulnerability, the mechanisms that contribute to this problem are not yet fully characterized. In previous works we demonstrated that changes in arterial wall viscosity and elasticity and/or in the filtering function (FF) could be in the basis of arterial wall alterations. If these properties are altered in arterial wall with atherosclerotic plaques remain to be analyzed. Our aims were to analyze, the arterial wall visco-elasticity and FF of human carotid arteries with atherosclerotic plaques. To this end, instantaneous arterial diameter waveforms were obtained non-invasively (B-Mode Echography), in five sites (S1-S5) on the carotid artery. After that, diameter waveform obtained in S1 (first segment of the common carotid artery) was calibrated using pressure values, and used to quantify the pressure-diameter relationship for each segment. From pressure-diameter relationships, viscosity, elasticity and FF were quantified. Central portions of atherosclerotic plaques showed a reduced FF. At least in theoretical terms, the FF reduction could be related with the plaque vulnerability.

Levels and rates of change in carotid-radial pulse wave velocity associated with reactive hyperaemia: Analysis of the dependence on transient ischemia length.

UNLABELLED: The analysis of carotid-radial pulse wave velocity (PWVcr) changes in response to forearm transient ischemia (TI) has been proposed as an alternative approach to evaluate endothelial function. Consider flow mediated dilatation tests, PWVcr changes are characterized after 5 minutes of TI. It is unknown if lower TI times could be used and if different TI times would result in different PWVcr responses (levels and/or kinetics). OBJECTIVE: To determine PWVcr changes associated with the reactive hyperemia in response to 1, 3 or 5 minutes of forearm TI. METHODS: We measured left PWVcr change using mechano-transducers in healthy volunteers (22 ± 2 years old) before (basal) and after 1 (n=14), 3 (n=14) and 5 (n=15) minutes of TI (forearm cuff inflation), respectively. The change of level and rate in PWVcr were recorded at 15, 30, 45 and 60 seconds after cuff release. Right brachial pressure was measured. RESULTS: There were no changes in heart rate or blood pressure during the studies. Regardless of the occlusion length, TI resulted in PWVcr reduction (p < 0.05). The groups showed similar maximum PWVcr reduction. However, there were differences in the immediate PWVcr changes (-4.9 ± 0.2%; -6.8 ± 0.3% and -8.3 ± 0.5% for 1, 3 and 5 minutes of TI, respectively) (p < 0.05). Then, the immediate rate of PWVcr change differed (p < 0.05) among the different ischemia times considered. Thereafter, the differences diminished and a minute after TI the groups showed similar levels and mean rate of PWVcr reduction. CONCLUSION: Similar maximum PWVcr responses can be obtained after 1, 3, or 5 minutes of TI. Different TI times resulted in dissimilar immediate, but not later, PWVcr changes.

Association between mechanics and structure in arteries and veins: theoretical approach to vascular graft confection.

Biomechanical and functional properties of tissue engineered vascular grafts must be similar to those observed in native vessels. This supposes a complete mechanical and structural characterization of the blood vessels. To this end, static and dynamic mechanical tests performed in the sheep thoracic and abdominal aorta and the cava vein were contrasted with histological quantification of their main constituents: elastin, collagen and muscle cells. Our results demonstrate that in order to obtain adequate engineered vascular grafts, the absolute amount of collagen fibers, the collagen/elastin ratio, the amount of muscle cells and the muscle cells/elastic fibers ratio are necessary to be determined in order to ensure adequate elastic modulus capable of resisting high stretches, an adequate elastic modulus at low and normal stretch values, the correct viscous energy dissipation, and a good dissipation factor and buffering function, respectively.

Non-symmetrical double-logistic analysis of 24 hour arterial stiffness profile in normotensive and hypertensive subjects.

OBJECTIVES: Mechanisms underlying the circadian profile of cardiovascular events (CE) are not totally understood. Whether circadian changes in arterial stiffness (AS) could be related to the circadian profile of CE remains to be investigated. As yet, there is no accepted way to measure circadian profiles or nocturnal-related and/or morning-related changes in cardiovascular variables. The aim of this study was to characterize the circadian pattern and day-night and night-day changes of AS in untreated hypertensive (HG) and healthy subjects (NG), using a recently developed non-symmetrical six-parameter double-logistic model. METHODS: Seven hypertensive and seven normotensive subjects underwent 24 hour ambulatory recordings of blood pressure (BP), heart rate (HR) and aorto-brachial pulse transit time (PTT(AB)) and pulse transit velocity index (PTV(AB)). PTT(AB) and PTV(AB) are inversely and directly related to AS, respectively. The circadian profile and transitional periods (day-night and night-day) were analyzed using a model described by a six-parameter double logistic equation. CONCLUSIONS: The model was adequate to characterize the circadian pattern of AS. We provide the first evidence that AS in humans follows an asymmetric circadian pattern and that this differs between NG and HG. In both NG and HG, AS had a circadian profile, with the highest levels in the night. HG showed larger levels of AS, larger BP variations and rate of change and minor changes in AS during transitional periods.

Cryografts implantation in human circulation would ensure a physiological transition in the arterial wall energetics, damping and wave reflection.

Each artery conduces blood (conduit function, CF) and smoothes out the pulsatility (buffering function, BF), while keeping its wall protected against the high oscillations of the pulse waves (damping function, xi). These functions depend on each segment viscoelasticity and capability to store and dissipate energy. When a graft/prosthesis is implanted, the physiological gradual transition in the viscoelasticity and functionality of adjacent arterial segments is disrupted. It remains to be elucidated if the cryografts would allow keeping the physiological biomechanical transition. The aim of this study was to evaluate the cryografts capability to reproduce the functional, energetic and reflection properties of patients' arteries and fresh homografts. Common carotid's pressure, diameter and wall-thickness were recorded in vivo (15 patients) and in vitro (15 cryografts and 15 fresh homografts from donors). Calculus: elastic (Epd) and viscous (Vpd) indexes, CF, BF, dissipated (WD) and stored (WPS) energy and xi. The graft-patient's artery matching was evaluated using the reflection coefficient (Gamma) and reflected power (WGamma). Cryografts did not show differences in Epd, Vpd, BF, CF, WD, WPS, and xi, in respect to fresh homografts and patients' arteries, ensuring a reduced Gamma and WGamma. Cryografts could be considered as alternatives in arterial reconstructions since they ensure the gradual transition of patients' arteries biomechanical and functional behavior.

Increased reversal and oscillatory shear stress cause smooth muscle contraction-dependent changes in sheep aortic dynamics: role in aortic balloon pump circulatory support.

AIMS: The intra-aortic balloon pumping (IABP) changes pressure and increases the aorta shear stress reversal (SS(R)) and oscillatory (SS(O)) components. Hence, IABP-dependent changes in aortic biomechanics would be expected, because of vascular smooth muscle (VSM) tone (i.e. flow-induced endothelium-dependent response, related to SS(R) and SS(O) variations) and/or pressure changes. To characterize: (i) the IABP effects on the aortic and global (systemic circulation) biomechanics, analysing their dependence on pressure and VSM basic tone changes and (ii) the relation between the SS(R) and SS(O) and the aortic biomechanical changes associated with the VSM tone variations. METHODS: Aortic flow, pressure and diameter were measured in eight sheep during basal, augmented and assisted beats (1 : 1 and 1 : 2 IABP modalities). Calculations: (i) aortic effective and isobaric elasticity, viscosity, circumferential stress, pulse wave velocity, shear stress and buffer and conduit functions, (ii) peripheral resistance, global compliance, reflection coefficient and wave propagation times and (iii) the relation between SS(R) and SS(O) and biomechanical changes associated with variations in the aortic VSM tone. RESULTS: Augmented and assisted beats showed: global VSM relaxation pattern (reduced peripheral resistance and reflection coefficient; increased propagation times) and local VSM contraction pattern (increased viscosity; reduced diameter, elasticity and circumferential stress), associated with SS(R) and SS(O), levels and changes. The vascular changes reduced the ventricle afterload determinants, increased the vascular buffer performance and kept the conduit capability. CONCLUSION: In addition to pressure-dependent changes, IABP determined biomechanical changes related to variations in the VSM tone. The increased SS(R) and SS(O) were associated with the aortic VSM contraction pattern and biomechanical changes.

[Vascular access for haemodyalisis. Comparative analysis of the mechanical behaviour of native vessels and prosthesis]. / Accesos vasculares para hemodialisis: analisis comparativo del comportamiento mecanico de vasos nati.

INTRODUCTION: The prosthesis nowadays used in the vascular access for haemodialysis have low patency rates, mainly due to the luminal obstruction, determined by the intimal hyperplasia. Several factors have been related to de development of intimal hyperplasia and graft failure. Among them are the differences in the biomechanical properties between the prosthesis and the native vessels. In the searching for vascular prosthesis that overcomes the limitations of the currently used, the cryopreserved vessels (cryografts) appear as an alternative of growing interest. However, it is unknown if the mechanical differences or mismatch between prosthesis and native vessels are lesser when using cryografts. OBJECTIVE: To characterize and compare the biomechanical behaviour of native vessels used in vascular access and cryografts. Additionally, segments of expanded polytetrafluoroethylene (ePTFE) were also evaluated, so as to evaluate the potential biomechanical advantages of the cryografts respect to synthetic prosthesis used in vascular access. METHODS: Segments from human humeral (n = 12), carotid (n = 12) and femoral (n = 12) arteries, and saphenous vein (n = 12), were obtained from 6 multiorgan donors. The humeral arteries were studied in fresh state. The other segments were divided into two groups, and 6 segments from each vessel were studied in fresh state, while the remaining 6 segments were evaluated after 30 days of criopreservation. For the mechanical evaluation the vascular segments and 6 segments of ePTFE were mounted in a circulation mock and submitted to haemodynamic conditions similar to those of the in vivo. Instantaneous pressure (Konigsberg) and diameter (Sonomicrometry) were measured and used to calculate the viscous and elastic indexes, the compliance, distensibility and characteristic impedance. For each mechanical parameter studied, the mismatch between the prosthesis and the native vessel was evaluated. RESULTS: The ePTFE was the prosthesis with the higher mechanical mismatch (p < 0.05). The venous and arterial cryografts showed the least mismatch with native veins and arteries, respectively. The prosthesis with the least mechanical mismatch was different, depending on the native vessel evaluated, and for a native vessel, on the parameter considered. CONCLUSION: The mechanical mismatch between the native vessel and the vascular prosthesis used in a vascular access could be reduced using cryografts.

Accesos vasculares para hemodiálisis: análisis comparativo del comportamiento mecánico de vasos nativos y prótesis / Vascular access for haemodyalisis. Comparative analysis of the mechanical vehaviour of native vessels and prosthesis

presentan elevadas tasas de falla por obstrucción luminal, secundaria a hiperplasia intimal. La generación de hiperplasia intimal y falla protésica se han vinculado, entre otros factores, con las diferencias biomecánicas entre las prótesis y los vasos nativos. En busca de prótesis que superen las limitaciones de las actuales, los vasos criopreservados (crioinjertos) son una alternativa de creciente interés. Sin embargo, se desconoce si las diferencias o desacoples mecánicos entre prótesis y vasos nativos son menores con los crioinjertos. Objetivo: Caracterizar y comparar el comportamiento biomecánico de vasos nativos utilizados en accesos vasculares y crioinjertos. Para analizar posibles ventajas biomecánicas de los crioinjertos en relación con la prótesis sintética más utilizada, se estudiaron segmentos de politetrafluoroetileno expandido (ePTFE). Métodos: Segmentos de arterias humeral (n = 12), carótida (n = 12) y femoral (n = 12), y vena safena (n = 12), fueron obtenidos de 6 donantes cadavéricos. Las arterias humerales se estudiaron en estado fresco. De los restantes vasos, 6 segmentos se evaluaron en estado fresco, y 6 luego de criopreservados durante 30 días. Para la evaluación biomecánica, los segmentos vasculares y 6 prótesis de ePTFE se montaron en un simulador circulatorio, y se sometieron a condiciones hemodinámicas similares a las de in vivo. Se midió presión (Konigsberg) y diámetro (sonomicrometría) instantáneo, y se calculó: el índice viscoso y elástico, la complacencia, distensibilidad e impedancia característica. Para cada parámetro, se cuantificó el desacople mecánico entre prótesis y vaso nativo. Resultados: El ePTFE presentó mayor desacople mecánico (p < 0,05). Los crioinjertos venosos y arteriales presentaron menor desacople mecánico con venas y arterias nativas, respectivamente. La prótesis con menor desacople mecánico fue diferente, dependiendo de parámetro biomecánico, y del vaso nativo considerado. Conclusión: El desacople mecánico con vasos nativos usados en accesos vasculares podría reducirse utilizando crioprótesis

Introduction: The prosthesis nowadays used in the vascular access for haemodialysis have low patency rates, mainly due to the luminal obstruction, determined by the intimal hyperplasia. Several factors have been related to de development of intimal hyperplasia and graft failure. Among them are the differences in the biomechanical properties between the prosthesis and the native vessels. In the searching for vascular prosthesis that overcome the limitations of the currently used, the cryopreserved vessels (cryografts) appear as an alternative of growing interest. However, it is unknown if the mechanical differences or mismatch between prosthesis and native vessels are lesser when using cryografts. Objective: To characterize and compare the biomechanical behaviour of native vessels used in vascular access and cryografts. Additionally, segments of expanded polytetrafluoroethylene (ePTFE) were also evaluated, so as to evaluate the potential biomechanical advantages of the cryografts respect to synthetic prosthesis used in vascular access. Methods: Segments from human humeral (n = 12), carotid (n = 12) and femoral (n = 12) arteries, and saphenous vein (n = 12), were obtained from 6 multiorgan donors. The humeral arteries were studied in fresh state. The other segments were divided into two groups, and 6 segments from each vessel were studied in fresh state, while the remaining 6 segments were evaluated after 30 days of criopreservation. For the mechanical evaluation the vascular segments and 6 segments of ePTFE were mounted in a circulation mock and submitted to haemodynamic conditions similar to those of in vivo. Instantaneous pressure (Konigsberg) and diameter (Sonomicrometry) were measured and used to calculate the viscous and elastic indexes, the compliance, distensibility and characteristic impedance. For each mechanical parameter studied, the mismatch between the prosthesis and the native vessel was evaluated. Results: The ePTFE was the prosthesis with the higher mechanical mismatch (p < 0.05). The venous and arterial cryografts showed the least mismatch with native veins and arteries, respectively. The prosthesis with the least mechanical mismatch was different, depending on the native vessel evaluated, and for a native vessel, on the parameter considered. Conclusion: The mechanical mismatch between the native vessel and the vascular prosthesis used in a vascular access could be reduced using cryografts

Adventitia-dependent mechanical properties of brachiocephalic ovine arteries in in vivo and in vitro studies.

AIM: An adventitia dependent regulation of the vascular smooth muscle tone has been described. However, if the adventitia plays an active role on arterial wall biomechanical behaviour and functions remains to be established. Our aim was to characterize the influence of adventitia on arterial wall mechanical properties and the arterial conduit and buffer functions. METHODS: Ovine brachiocephalic arteries were studied in vivo (n = 8) and in vitro (with null tone) in a circulation mock (n = 8). Isobaric, isoflow and isofrequency studies were performed. In each segment, pressure and diameter waves were assessed before and after adventitia removal. From the arterial stress-strain relationship, we derived the elastic and the viscous modulus. The buffering and conduit functions were calculated using the Kelvin-Voigt's time constant and the inverse of the characteristic impedance, respectively. RESULTS: In in vivo studies arterial diameter decreased after adventitia removal (P < 0.05). Elastic and viscous modulus in in vivo studies were significantly higher in adventitia-removed arteries, compared with values in intact vessels (P < 0.05). This behaviour was not observed in in vitro experiments. An impairment of buffer and conduit functions was observed in vivo after adventitia removal (P < 0.05), while both functions remain unchanged in in vitro studies (P > 0.05). CONCLUSIONS: Arterial wall viscosity and elasticity were influenced by adventitia removal in in vivo studies, possibly by a smooth muscle-dependent mechanism, since it was not present in in vitro experiments. Adventitia would be involved in a physiological mechanism of arterial wall viscous and elastic properties regulation, that could influence arterial buffering and conduit functions.

Dynamics of cryopreserved human carotid arteries.

The viscoelastic properties of the arterial wall are responsible for their functional role in the arterial system. Cryopreservation is widely used to preserve blood vessels for vascular reconstruction but is controversially suspected to affect the dynamic behaviour of these allografts. The aim of this study was to determine whether differences in the dynamic behaviour exist or not between fresh and cryopreserved human common carotid arteries (CCA). Using a previously developed mock circulation system, dynamic pressure-diameter tests were performed on segments of human fresh (n=10) and cryopreserved arteries (n=7). A diameter-pressure transfer function was designed to evaluate the wall dynamics. An adaptive model was fit to obtain its frequency response. Three models were tested. Results show that non-significant differences exist between wall dynamics of fresh and cryopreserved segments of human CCA.

Diferencias regionales en la biomecánica y amortiguamiento arterial sistémico y pulmonar / Regional differences in the biomechanical and systemic and pulmonary arterial buffer

Systemic arteries show higher vascular disease than pulmonary ones. The aim of this study was to establish regional and functional differences in the mechanical properties of arteries in both circulations. Pressure (Konigsberg) and diameter (Sonomicrometry) were measured in seven artery segments corresponding to each sheep (N=7) using a previously developed mock circulation loop...