Increasing pulse wave velocity in a realistic cardiovascular model does not increase pulse pressure with age

The mechanism of the well-documented increase in aortic pulse pressure (PP) with age is disputed. Investigators assuming a classical windkessel model believe that increases in PP arise from decreases in total arterial compliance (C(tot)) and increases in total peripheral resistance (R(tot)) with age. Investigators assuming a more sophisticated pulse transmission model believe PP rises because increases in pulse wave velocity (c(ph)) make the reflected pressure wave arrive earlier, augmenting systolic pressure. It has recently been shown, however, that increases in c(ph) do not have a commensurate effect on the timing of the reflected wave. We therefore used a validated, large-scale, human arterial system model that includes realistic pulse wave transmission to determine whether increases in c(ph) cause increased PP with age. First, we made the realistic arterial system model age dependent by altering cardiac output (CO), R(tot), C(tot), and c(ph) to mimic the reported changes in these parameters from age 30 to 70. Then, c(ph) was theoretically maintained constant, while C(tot), R(tot), and CO were altered. The predicted increase in PP with age was similar to the observed increase in PP. In a complementary approach, C(tot), R(tot), and CO were theoretically maintained constant, and c(ph) was increased. The predicted increase in PP was negligible. We found that increases in c(ph) have a limited effect on the timing of the reflected wave but cause the system to degenerate into a windkessel. Changes in PP can therefore be attributed to a decrease in C(tot).     

ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects

The capacity of HDL to induce cell cholesterol efflux is considered one of its main antiatherogenic properties. Little is known about the impact of such HDL function on vascular physiology. We investigated the relationship between ABCA1-dependent serum cholesterol efflux capacity (CEC), an HDL functionality indicator, and pulse wave velocity (PWV), an indicator of arterial stiffness. Serum of 167 healthy subjects was used to conduct CEC measurement, and carotid-femoral PWV was measured with a high-fidelity tonometer. J774 macrophages, labeled with [³H]cholesterol and stimulated to express ABCA1, were exposed to sera; the difference between cholesterol efflux from stimulated and unstimulated cells provided specific ABCA1-mediated CEC. PWV is inversely correlated with ABCA1-dependent CEC (r = −0.183; P = 0.018). Moreover, controlling for age, sex, body mass index, mean arterial pressure, serum LDL, HDL-cholesterol, and fasting plasma glucose, PWV displays a significant negative regression on ABCA1-dependent CEC (β = −0.204; 95% confidence interval, −0.371 to −0.037). The finding that ABCA1-dependent CEC, but not serum HDL cholesterol level (r = −0.002; P = 0.985), is a significant predictor of PWV in healthy subjects points to the relevance of HDL function in vascular physiology and arterial stiffness prevention.     

Noninvasive quantitative determination of the modulus of characteristic impedance of human limb arteries

A noninvasive method of quantitative evaluation of characteristic impedance modulus of human limb arteries based on blood pressure and blood vessel volume parameters is described. The differences in the value of characteristic impedance modulus in the upper and lower limb arteries in supine and resting subjects have been shown. Under postural effects the impedance changes in the lower limb arteries are proportional to those of mean blood pressure in these vessels. No significant impedance alterations on effort have been observed in these arteries. The impedance of the upper limb arteries increased in passive orthostatic position and after physical exercises of the lower limbs. Characteristic impedance modulus of these arteries decreased after physical exercises of the upper limbs.     

An innovative numerical approach to resolve the pulse wave velocity in a healthy thoracic aorta model

Aortic dissection and atherosclerosis are highly fatal diseases. The development of both diseases is closely associated with highly complex haemodynamics. Thus, in predicting the onset of cardiac disease, it is desirable to obtain a detailed understanding of the flowfield characteristics in the human cardiovascular circulatory system. Accordingly, in this study, a numerical model of a normal human thoracic aorta is constructed using the geometry information obtained from a phase-contrast magnetic resonance imaging (PC-MRI) technique. The interaction between the blood flow and the vessel wall dynamics is then investigated using a coupled fluid–structure interaction (FSI) analysis. The simulations focus specifically on the flowfield characteristics and pulse wave velocity (PWV) of the blood flow. Instead of using a conventional PC-MRI method to measure PWV, we present an innovative application of using the FSI approach to numerically resolve PWV for the assessment of wall compliance in a thoracic aorta model. The estimated PWV for a normal thoracic aorta agrees well with the results obtained via PC-MRI measurement. In addition, simulations which consider the FSI effect yield a lower predicted value of the wall shear stress at certain locations in the cardiac cycle than models which assume a rigid vessel wall. Consequently, the model provides a suitable basis for the future development of more sophisticated methods capable of performing the computer-aided analysis of aortic blood flows.     

Determination of wave speed and wave separation in the arteries using diameter and velocity

The determination of arterial wave speed and the separation of the forward and backward waves have been established using simultaneous measurements of pressure (P) and velocity (U). In this work, we present a novel algorithm for the determination of local wave speed and the separation of waves using the simultaneous measurements of diameter (D) and U. The theoretical basis of this work is the solution of the 1D equations of flow in elastic tubes. A relationship between D and U is derived, from which, local wave speed can be determined; C=±0.5(dU_±/d ln D_±). When only unidirectional waves are present, this relationship describes a linear relationship between ln D and U. Therefore, constructing a ln DU-loop should result in a straight line in the early part of the cycle when it is most probable that waves are running in the forward direction. Using this knowledge of wave speed, it is also possible to derive a set of equations to separate the forward and backward waves from the measured D and U waveforms. Once the forward and backward waveforms of D and U are established, we can calculate the energy carried by the forward and backward waves, in a similar way to that of wave intensity analysis. In this paper, we test the new algorithm in vitro and present results from data measured in the carotid artery of human and the ascending aorta of canine. We conclude that the new technique can be reproduced in vitro, and in different vessels of different species, in vivo. The new algorithm is easy to use to determine wave speed and separate D and U waveforms into their forward and backward directions. Using this technique has the merits of utilising noninvasive measurements, which would be useful in the clinical setting.     

Structural changes of immunoglobulin G oligosaccharides with age in healthy human serum

Age-related changes of IgG N-linked oligosaccharides isolated from normal human serum are reported for 403 individuals (male 227 and female 176), varying in age from 0 to 85 years. The IgG N-linked oligosaccharides were released from the protein by digestion with a glycoamidase and reductively aminated with the fluorescent reagent, 2-aminopyridine. The mixture of pyridylaminated oligosaccharides was separated at high resolution by HPLC using a reverse-phase column. From the results of neutral oligosaccharide analysis, agalactosyl glycoform and bisecting GlcNAc-containing glycoform were shown to increase with increasing age. Spearman's correlation coefficients were 0.503 and 0.473, respectively. Thus, in healthy people, an increase of both types of glycoforms correlates weakly with age. In addition, differences were demonstrated between male and female groups in their twenties. The quantity of agalactosyl glycoform was found to be lower in females than in males. No significant differences, however, were observed in the quantity of bisecting GlcNAc-containing glycoforms between males and females. Abbreviations: Gal, D-galactose: GlcNAc, N-acetyl-D-glucosamine; Man, D-mannose; Fc, C-terminal half of the heavy chain dimers of IgG; HPLC, high-performance liquid chromatography; IgG, immunoglobulin G; ODS, octadecylsilyl; PA, pyridylamino This revised version was published online in November 2006 with corrections to the Cover Date.     

The velocity of the arterial pulse wave: a viscous-fluid shock wave in an elastic tube

Background

The arterial pulse is a viscous-fluid shock wave that is initiated by blood ejected from the heart. This wave travels away from the heart at a speed termed the pulse wave velocity (PWV). The PWV increases during the course of a number of diseases, and this increase is often attributed to arterial stiffness. As the pulse wave approaches a point in an artery, the pressure rises as does the pressure gradient. This pressure gradient increases the rate of blood flow ahead of the wave. The rate of blood flow ahead of the wave decreases with distance because the pressure gradient also decreases with distance ahead of the wave. Consequently, the amount of blood per unit length in a segment of an artery increases ahead of the wave, and this increase stretches the wall of the artery. As a result, the tension in the wall increases, and this results in an increase in the pressure of blood in the artery.

Methods

An expression for the PWV is derived from an equation describing the flow-pressure coupling (FPC) for a pulse wave in an incompressible, viscous fluid in an elastic tube. The initial increase in force of the fluid in the tube is described by an increasing exponential function of time. The relationship between force gradient and fluid flow is approximated by an expression known to hold for a rigid tube.

Results

For large arteries, the PWV derived by this method agrees with the Korteweg-Moens equation for the PWV in a non-viscous fluid. For small arteries, the PWV is approximately proportional to the Korteweg-Moens velocity divided by the radius of the artery. The PWV in small arteries is also predicted to increase when the specific rate of increase in pressure as a function of time decreases. This rate decreases with increasing myocardial ischemia, suggesting an explanation for the observation that an increase in the PWV is a predictor of future myocardial infarction. The derivation of the equation for the PWV that has been used for more than fifty years is analyzed and shown to yield predictions that do not appear to be correct.

Conclusion

Contrary to the theory used for more than fifty years to predict the PWV, it speeds up as arteries become smaller and smaller. Furthermore, an increase in the PWV in some cases may be due to decreasing force of myocardial contraction rather than arterial stiffness.     

Straightening of aberrant carotid arteries with age in velocardiofacial syndrome.

Two cases of velocardiofacial syndrome demonstrated spontaneous straightening over a 4-year period of previously deviated carotid arteries on contrast enhanced computed tomography. Based on this finding, uncomplicated traditional pharyngeal flaps were performed on both patients. It is unknown whether straightening of aberrant vessels with age is the rule or the exception in this patient population.     

Energy dissipation and pulse wave attenuation in the canine carotid artery

This paper presents methods for calculating, for a segment of artery in vivo, (1) viscous and viscoelastic energy dissipation as a function of time, and (2) the viscous and viscoelastic components of the frequency-dependent attenuation coefficient. The calculations require measurement of arterial diameter and of intra-arterial pressure and flow-rate at two sites along the vessel. Viscous energy dissipation is calculated from the radius-dependent velocity shear in the lumen given by linear theory from the pressure measurements. The attenuation coefficient for a given harmonic of heart rate is calculated as half the sum of the viscous and viscoelastic components at that frequency of the energy dissipated per unit length by forwardtravelling waves, divided by the forward-wave flow work input to the segment at that frequency. Measurements in canine carotid arteries indicate that wall viscoelasticity contributes relatively little to energy dissipation per cardiac cycle and pulse wave attenuation.     

Contractile and relaxing reactivity in carotid and femoral arteries of chicken embryos

In the embryo, hypoxemia causes redistribution of cardiac output from the periphery toward the heart and the brain. In view of this, we investigated developmental changes in the contractile and relaxing properties of the peripheral femoral artery (Fem) and the more central carotid artery (Car) at 0.7, 0.8, and 0.9 of the chicken embryo incubation time. Isolated arteries were studied in myographs and were exposed to norepinephrine or phenylephrine. High K(+) (125 mM) and electrical field stimulation (0.25-16 Hz) were used to induce receptor-independent and neurogenic contractions. Relaxing responses to ACh were evaluated in the absence and presence of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and before and after endothelium removal. alpha(1)-Adrenergic contractile responses increased in a time-dependent manner and were significantly larger in Fem than in Car. Neurogenic contractions and adrenergic nerves could only be demonstrated in Fem at 0.9 incubation. ACh caused relaxation in both Fem and Car at 0.7, 0.8, and 0.9 incubation. The NO-independent part of the relaxation was more pronounced in Car than in Fem at all developmental stages. We conclude that the chicken embryo is a useful model to investigate the development of vasomotor control and vascular heterogeneity. The observed regional vascular differences may contribute to cardiac output redistribution during hypoxia in the embryo and might result from endothelial and neurogenic influences on vascular smooth muscle differentiation.     

Thermomechanical behavior of human carotid arteries in the passive state

Localized heating or cooling is expanding the clinical procedures used to treat cardiovascular diseases. Advantageous implementation and development of these methods are linked indissolubly to a deeper understanding of the arterial response to combined mechanical and thermal loads. Despite this, the basic thermomechanical behavior of human blood vessels still remains largely unknown, primarily due to the lack of appropriate experimental data. In this work, the influence of temperature on the passive behavior of human carotid arteries was studied in vitro by means of inflation tests. Eleven carotid segments were tested in the range 0-200 mmHg at four different temperatures of 17, 27, 37, and 42 degrees C. The results show that the combined change of temperature and stress has a dramatic effect on the dilatation coefficient of the arterial wall, which is shifted from negative to positive depending on the stress state, whereas the structural stiffness of the arterial wall does not change appreciably in the range of temperatures tested.     

Evaluation of blood flow velocity waveform in common carotid artery using multi-branched arterial segment model of human arteries

Arteriosclerosis is considered to be a major cause of cardiovascular diseases, which account for approximately 30% of the causes of death in the world. We have recently demonstrated a strong correlation between arteriosclerosis (arterial elasticity) and two characteristics: maximum systolic velocity (S1) and systolic second peak velocity (S2) of the common carotid artery flow velocity waveform (CCFVW). The CCFVW can be measured by using a small portable measuring device. However, there is currently no theoretical evidence supporting the causes of the relation between CCFVW and arterial elasticity, or the origin of the CCFVW characteristics. In this study, the arterial blood flow was simulated using a one-dimensional systemic arterial segments model of human artery in order to conduct a qualitative evaluation of the relationship between arterial elasticity and the characteristics of CCFVW. The simulation was carried out based on the discretized segments with the physical properties of a viscoelastic tube (the cross-sectional area at the proximal and terminal ends, the length, and the compliance per unit area of the tube (C_S)). The findings obtained through this study revealed that the simulated CCFVW had shape similar characteristics to that of the measured CCFVW. Moreover, when the compliance C_S of the model was decreased, the first peak of the simulated-CCFVW decreased and the second peak increased. Further, by separating the anterograde pulse wave and the reflected pulse wave, which form the CCFVW, we found that the decrease in the first peak of the simulated CCFVW was due to the arrival of a reflected pulse wave from the head after the common carotid artery toward the arrival of a anterograde pulse wave ejected directly from the heart and that the increase in the second peak resulted from the arrival of the peak of the reflected pulse wave from the thoracic aorta. These results establish that the CCFVW characteristics contribute to the assessment of arterial elasticity.     

Effects of acute cold exposure on carotid and femoral wave intensity indexes: evidence for reflection coefficient as a measure of distal vascular resistance

Our aim was to investigate the effects of acute cold pressor test (CPT) on augmentation index (AI) and wave intensity (WI) indexes from right common carotid artery (RCCA) and right common femoral artery (RCFA) and to test whether the reflection coefficient (RC) from wave intensity analysis can reflect the distal vascular resistance (DVR) accurately. Forty-three healthy males were randomly selected for measurements at baseline and 1 min after CPT at RCCA or RCFA. CPT induced similar increases of heart rate and blood pressure in RCCA and RCFA groups with their pulse pressures unchanged. The W(2) (the second peak of WI) was too obscure in RCFA to be analyzed. The W(1) (the first peak of WI) of both arteries, W(1)-W(2) (interval between W(1) and W(2)), and NA (negative area between W(1) and W(2), indicating reflected waves) of RCCA and the R-W(1) (interval between the R wave of ECG and W(1)) of RCFA decreased obviously, whereas the W(2) and R-W(1) of RCCA and the RC (calculated as NA/W(1)) of RCFA increased with no changes in the RC of RCCA and the NA of RCFA during CPT compared with baseline. The AIs from both arteries increased significantly after CPT. These results suggested that acute CPT has opposing effects on cerebral and peripheral vascular resistances, with the former decreased and the latter increased. The RCs from RCCA and RCFA are more associated with the changes of cerebral and peripheral vascular resistances, respectively, than the NA and AI, and the RC is of guiding value in assessing DVR.     

Sphingolipid distribution changes with age in the human lens

The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens sections were initially analyzed by MALDI mass spectrometry imaging. A distinct annular distribution of the dihydrosphingomyelin, DHSM (d18:0/16:0), in the barrier region was observed in 64- and 70-year-old lenses but not in a 23-year-old lens. An increase in the dihydroceramide, DHCer (d18:0/16:0), in the lens nucleus was also observed in the older lenses. These findings were supported by ESI mass spectrometry analysis of lipid extracts from lenses dissected into outer, barrier, and nuclear regions. A subsequent analysis of 18 lenses ages 20–72 years revealed that sphingomyelin levels increased with age in the barrier region until reaching a plateau at approximately 40 years of age. Such changes in lipid composition will have a significant impact on the physical properties of the fiber cell membranes and may be associated with the formation of a barrier.     

Functional properties of fresh and cryopreserved carotid and femoral arteries,and of venous and synthetic grafts: comparison with arteries from normotensive and hypertensive patients

The ideal arterial graft must share identical functional properties with the host artery. Surgical reconstruction of the common carotid artery (CA) is performed in several clinical situations, using expanded polytetrafluoroethylene prosthesis (ePTFE) or saphenous vein (SV) grafts. At date there is interest in obtaining an arterial graft that improves the results of that nowadays available. The use of a fresh or cryopreserved/defrosted artery appears as an interesting alternative. However, if the fresh and cryopreserved/defrosted arteries allow an adequate viscoelastic and functional matching with the host arteries needs to be established. The aims were to compare the viscoelastic and functional performance of: (1) conduits used in CA reconstruction (SV and ePTFE) with those of the fresh and cryopreserved/defrosted CA and femoral arteries (FA), and (2) normotensive and hypertensive patients’ arteries with those of the arterial substitutes in vitro analyzed. Pressure, diameter and wall thickness of the CA were recorded in 15 normotensive and 15 hypertensive patients (in vivo studies), and in SV, fresh and cryopreserved/defrosted CA and FA (obtained from 15 donors), and ePTFE segments (in vitro studies). From stress–strain relationship we calculated elastic and viscous modulus, and the characteristic impedance. The local buffer and conduit functions were quantified as the viscous/elastic quotient and the inverse of the characteristic impedance. Fresh and cryopreserved/defrosted CA and FA were more alike, both in viscoelastic and functional levels, respect to normotensive and hypertensive patients’ arteries, than the ePTFE and SV grafts. CA and FA cryografts could be considered an important alternative for carotid reconstruction.     

Morphological changes in the central nervous system of dogs with unilateral lesions of carotid arteries]

16 dogs were subjected to either ligation or kinking of a single carotid artery and the resultant changes in the cortical hemisphere were studied. Light and electron microscopy findings indicate reversibility of the induced pathological processes both in microcirculation and in neurons proper.