Pulse pressure and arterial elasticity.
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Arteries↗
Biomedical subjects
S E Greenwald
Publications and source records attributed to S E Greenwald.
A hypothesis about a mechanism for the programming of blood pressure and vascular disease in early life.
1. There is now a great deal of evidence that people whose weight at birth was low tend to have higher blood pressure and increased risk of death from cardiovascular disease as adults. 2. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries is deficient and that this deficiency leads to permanent changes in the mechanical properties of these vessels. 3. Over a lifetime, such changes could predispose an individual to higher blood pressure and cardiovascular disease.
Adult↗
Improving vascular grafts: the importance of mechanical and haemodynamic properties.
In the last 40 years, as techniques and materials have improved, the success rate of vascular prostheses with a diameter greater than 6mm has risen steadily, 5-year survival rates exceeding 95% in most centres. With smaller grafts no comparable improvement has occurred, the majority failing within 5 years, usually as a result of intimal hyperplasia and, ultimately atherosclerosis, in and around the downstream anastomosis. Clinical evidence suggests that the patency rates of small grafts are improved by matching the elastic properties of the graft to that of the artery into which it is placed. Although there is little reliable evidence that 'elastic mismatch' per se is the cause of intimal hyperplasia, it is generally accepted that mechanical factors are important in its genesis. These include disturbed flow at the anastomosis leading to fluctuations in shear stress at the endothelium (a known cause of intimal hyperplasia in normal arteries), injury due to suturing and stress concentration at the anastomosis. Few suitable materials or techniques have yet been developed to improve the long-term survival rates of small grafts. Recent advances in tissue engineering in which prostheses are manufactured by culturing vascular smooth muscle cells on a tubular scaffold of biodegradable polymer may ultimately make it possible to manufacture biologically and haemodynamically compatible grafts with diameters as small as 1mm.
Arteries↗
Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension.
There is much evidence that people who had low birthweight tend to have higher blood pressure in later life. However, the mechanisms that mediate this relation are unknown. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries may be deficient, and that this deficiency would lead to permanent changes in the mechanical properties of these vessels. Over a lifetime, such changes could predispose an individual to higher blood pressure, increased left-ventricular mass, and cardiovascular disease.
Aging↗
Comparison of different methods for the determination of the true wave propagation coefficient, in rubber tubes and the canine thoracic aorta.
The results from studies of wave propagation in large arteries carried out over the last 25 years have shown that there is a good agreement among values of the imaginary part of the complex propagation coefficient, as expressed by pressure or flow-rate wave propagation velocity. However, there is considerable disparity among estimations of the degree of wave attenuation, the real part of the propagation coefficient. In order to determine whether this disparity is due to differences inherent in the various methods used to measure true wave propagation coefficients or whether it is caused by differences in experimental conditions, we have compared three techniques for determining true pulse wave propagation coefficients the three-point method, the occlusion method and a recently described iterative procedure. In addition, the results were compared to apparent propagation coefficients calculated without accounting for reflections. Measurements were carried out using each method in turn on a rubber tube of known transmission characteristics in which the magnitude of reflections was small. The iterative procedure and the three-point method were also compared under conditions of strong reflection. In the tube, the values of propagation velocity and attenuation coefficient determined by each method were similar. Although some discrepancies were noted, they did not amount to a systematic trend. The iterative procedure and the occlusion method were also used to analyse measurements on the thoracic aorta of three anaesthetized greyhounds. In the animal experiments, in spite of increased scatter, partly due to the variation between dogs, the two methods for determining true pulse-wave propagation yielded similar results. Since the differences between our estimates of propagation coefficients obtained by the methods tested are small with respect to those found when comparing the results from several reports in the literature, we conclude that any discrepancies between studies cannot be due to problems associated with the methods themselves but must have been caused by variations in experimental conditions or by other unknown artefacts.
Animals↗
Experimental investigation of the distribution of residual strains in the artery wall.
Arterial wall stresses are thought to be a major determinant of vascular remodeling both during normal growth and throughout the development of occlusive vascular disease. A completely physiologic mechanical model of the arterial wall should account not only for its residual strains but also for its structural nonhomogeneity. It is known that each layer of the artery wall possesses different mechanical properties, but the distribution of residual strain among the different mechanical components, and thus the true zero stress state, remain unknown. In this study, two different sets of experiments were carried out in order to determine the distribution of residual strains in artery walls, and thus the true zero stress state. In the first, collagen and elastin were selectively eliminated by chemical methods and smooth muscle cells were destroyed by freezing. Dissolving elastin provoked a decrease in the opening angle, while dissolving collagen and destroying smooth muscle cells had no effect. In the second, different wall layers of bovine carotid arteries were removed from the exterior or luminal surfaces by lathing or drilling frozen specimens, and then allowing the frozen material to thaw before measuring residual strain. Lathing material away from the outer surface caused the opening angle of the remaining inner layers to increase. Drilling material from the inside caused the opening angle of the remaining outer layers to decrease. Mechanical nonhomogeneity, including the distribution of residual strains, should thus be considered as an important factor in determining the distribution of stress in the artery wall and the configuration of the true zero stress state.
Analysis of Variance↗
Pulse wave velocity as a marker of vascular disease.
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Aorta, Thoracic↗
The effect of age on residual strain in the rat aorta.
Residual stress is observed in many parts of the cardiovascular system and is thought to reduce transmural stress gradients due to intravascular pressure. Its development is closely associated with normal growth and pathological remodeling, although there appear to be few previous reports of the relationship between aging and residual stress. We have estimated residual strain (an indicator of the magnitude of residual stress) at ten sites along the aorta of rats aged 2.5 to 56 weeks by measuring the degree to which rings of vessel spring open when cut (opening angle). At all ages the opening angle decreased along the aorta, reaching a minimum near the renal arteries and increasing toward the aorto-iliac bifurcation, a result that confirms previous studies. During growth, although the unloaded circumference of the aorta increased steadily, the wall thickness and medial surface area fell to a minimum at the age of 6 weeks before continuing a steady increase. Similarly, the opening angle decreased between the ages of 2.5 and 6 weeks, thereafter increasing with age. In the abdominal aorta, a strong correlation between opening angle and wall thickness relative to midwall radius (h/R) was seen; whereas in the thoracic segment, in which no increase in h/R with age occurred, no such relationship was found. These observations are in keeping with a recently proposed hypothesis that residual stress will change in response to growth-related changes in vessel geometry driven by a tendency to minimize the nonuniform stress distribution inevitably found in pressurized thick-walled cylinders.
Aging↗
Desmin expression in rhabdomyosarcoma: influence of the desmin clone and immunohistochemical method.
AIM: To determine which, if any, of five commercially available desmin clones is most reliable at labelling desmin filaments and whether the enhanced polymer one step (EPOS) method of labelling is of any advantage in the routine diagnostic laboratory. METHODS: Thirty four rhabdomyosarcomas from the files at The Hospital for Sick Children, Great Ormond Street, London, were studied. Four different desmin clones, DE-R-11, D33, DE-U-10, and PDE, were applied to each using the conventional extravidin biotin peroxidase method. The D33 clone was also applied using the EPOS method. RESULTS: The EPOS method incorporating D33 persistently scored more cells as desmin positive and was positive in four cases which were negative on staining with the other clones. CONCLUSIONS: The D33 desmin clone used with the EPOS method is more reliable for identifying desmin filaments in tumours than other desmin antibodies tested. Different desmin clones using a routine technique label different rhabdomyosarcoma cells and therefore it is justifiable to use more than one clone.
Desmin↗
The relationship between wall tension, lamellar thickness, and intercellular junctions in the fetal and adult aorta: its relevance to the pathology of dissecting aneurysm.
It is known that the distribution of stress and strain in the vessel wall is not uniform. We believe that this explains the location of the plane of dissection in dissecting aneurysms of large elastic arteries. We have investigated the effects of non-uniformity of stress and strain on the thickness of each elastic lamella and on the distribution of intercellular junctions in the media of developing and adult rats, to seek evidence to support this hypothesis. Intercellular junctions were identified by transmission electron microscopy of whole wall sections. A morphometric study of elastic tissue distribution was made on an image analysis computer. Differences were analysed using one-way analysis of variance. There are between six and eight elastic lamellae in the aorta of rats. In the fetus, only the internal elastic lamella is complete; the others were not fully formed by term. In the adult, the inner five elastic lamellae were thicker than the remaining two or three, and smooth muscle cells in the thicker lamellar units had more cell-cell contacts of all types examined. These data support the concept of a difference in stress-resisting properties of the aortic wall on the junctions between the inner two-thirds and the outer third of the media. The findings indicate that, as proposed in theoretical models the innermost lamellae support the high tension. In the adult aorta, the structure is modified to enhance the capacity to resist stress in the internal two-thirds of the media.(ABSTRACT TRUNCATED AT 250 WORDS)
Aortic Dissection↗
Morbid anatomy in neonates with Ebstein's anomaly of the tricuspid valve: pathophysiologic and clinical implications.
The hearts of six neonates with Ebstein's anomaly of the tricuspid valve who died in the 1st month of life were compared with hearts of six age- and size-matched control neonates. All six hearts had morphologically severe disease with gross right atrial dilation and marked apical displacement of the tricuspid valve. All had a secundum atrial septal defect and four had additional cardiac lesions (pulmonary atresia in two, ventricular septal defect in two). There was significant thinning of the right ventricular free wall distal to the tricuspid valve (3 +/- 0.2 mm vs. control 4.2 +/- 0.2, p less than 0.01) and right ventricular fiber diameter was reduced (7.2 +/- 0.3 microns vs. control 11.4 +/- 0.6, p less than 0.001). The fibrous tissue content of both right and left ventricular free walls was increased (right, 29.3 +/- 2.6% vs. control 8.7 +/- 1.1, p less than 0.001; left, 23.2 +/- 1.5% vs. control 8.5 +/- 0.7%, p less than 0.001). Although the right ventricular abnormalities might be explained by hemodynamic stress in utero, abnormalities of the left ventricular free wall suggest that either genetic or nonhemodynamic environmental factors are involved in the morphogenesis of this condition. Increased right and left ventricular fibrosis may contribute to the poor early outcome in this group and may predispose to late complications, such as subnormal exercise performance, hemodynamic deterioration or late sudden death that may occur in patients with Ebstein's anomaly who survive the neonatal period.
Ebstein Anomaly↗
A general method of determining the frequency-dependent propagation coefficient and characteristic impedance of an artery in the presence of reflections.
An iterative method of calculating propagation parameters at harmonics of heart rate for a uniform vascular segment from a combination of four arterial waveform measurements is presented. Measurements of blood pressure, vascular diameter, and blood flow-rate may be combined arbitrarily provided only that at least one measurement of pressure and one of flow-rate be included; the requirement of four measurements implies at least two measurement sites along the vessel. The analysis is thus a generalization of those associated with previous methods of determining propagation parameters, allowing for instance relaxation of the requirement of equal spacing in the three-point method. Results are presented for the propagation of an impulse along a rubber tube when the measurements are pressure at two sites, flow-rate and diameter.
Arteries↗
The development of an in-vitro perfusion system for studies on cultured cells.
The design and use of a perfusion system, using a modified flow chamber for studies on cultured animal cells, is described. Rat thoracic aorta smooth muscle cells were isolated by an explant method and grown on Thermanox coverslips. These were introduced into the flow chamber. A flow rate of 25ml/min and a shear stress of 14.6 dynes/cm2 (12 dyne = 10 microN) (both within physiological limits) were maintained. Cells remained attached to the coverslips after 8h of perfusion with culture medium. The effect of exposing rat smooth muscle cells to the cardiovascular toxin, allylamine, is also described. The components of the system are routinely available, simple to clean, easy to assemble and sterilize. The incorporation of an in-line sensor that monitors pH, PO2, PCO2 and temperature ensures that the perfusion conditions remain within physiological limits. Automation means that minimal supervision is required. This system provides a potential mechanism in which cultured vascular cells may be perfused under controlled haemodynamic conditions, and their response to a cytotoxin may be evaluated.
Allylamine↗
Effect of age on the in vitro reflection coefficient of the aortoiliac bifurcation in humans.
The local reflection coefficient (r) at the aortoiliac junction was estimated in vessels removed at autopsy from 15 females and 31 males aged 2 months to 88 years by calculating the characteristic impedance (Zc) of the abdominal aorta and the two common iliac arteries. Zc was evaluated for each vessel by measuring cross-sectional area from radiographs and propagation velocity of an isolated pressure impulse generated by a solenoid-driven piston connected to the distal end of the abdominal aorta, and detected at several sites a known distance from the junction. Attenuation coefficients in the aorta were estimated from the peak amplitude of the impulse at these several sites. We observed significant decreases with age in abdominal aortic attenuation coefficient (gamma = 0.053-5 x 10(-4) age [yr], r = -0.42, p less than 0.005), and the area ratio (AR) of the junction (sum of the iliac cross-sectional areas/aortic cross-sectional area) (AR = 0.93-0.002 x age [yr], r = -0.31, p less than 0.05). Bifurcation angle (Angle) and aortic propagation velocity (caorta) increased significantly (angle = 40.2 + 0.26 x age [yr], r = 0.41, p less than 0.01; caorta (ms-1) = 7.59 + 0.175 x age [yr], r = 0.69, p less than 0.0001). No significant association between age and iliac propagation velocity was found. On the basis of area measurements alone, it has been argued that the observed decrease in area ratio with age causes r to become more positive. The lack of age-related changes in iliac propagation velocity (and hence stiffness), an observation confirmed by most of the few reports in the literature, and the large increase in abdominal aortic stiffness, however, greatly outweighed the area ratio changes and caused a significant decline in reflection coefficient from +0.3 in early life to -0.3 in old age. (Reflection coefficient = 0.30-0.0065 x age [yr], r = -0.68, p less than 0.0001). Between the ages of 30 and 60 years, its absolute value was less than 0.1, confirming in vivo work on subjects within this age range. In children, a significant positive reflection at the distal end of the aorta will amplify the pulse wave in this region. As this vessel becomes stiffer with increasing age, amplification will increase, whereas the increasingly negative value of r will partially offset this rise, reducing pulse pressure on either side of the junction.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
In vitro determination of lung airway compliance in small animals.
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Animals↗
The validity of negative necropsy reports from metastases in solid organs.
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Autopsy↗
High frequency characteristics of the arterial system.
Pressure, flow and diameter were measured in the abdominal aorta of five anesthetized dogs during normal heart beats and heart beats with a superimposed impulse (generated by rapidly injecting a small volume of saline into the system). From Fourier analysis it was found that the impulse enhanced the amplitudes of the higher harmonics so that frequencies up to 80 Hz could be studied. Both the input impedance and apparent phase velocity above 20 Hz were independent of frequency and their average values were designated as characteristic impedance and true phase velocity. Average characteristic impedance for all five animals was 2.0 +/- 0.1 X 10(8) Nsm-5 and average phase velocity was 8.3 +/- 0.6 ms-1. Phase velocities calculated from characteristic impedance (1.76-2.39 X 10(8) Nsm-5) and from the slope of the pressure-diameter relation (0.102-0.25 X 10(-8) Nm-3) were similar to the true phase velocity as defined above (6.79-9.85 ms-1). It may be concluded that the input impedance converges to characteristic impedance and apparent phase velocity converges to phase velocity for high frequencies.
Animals↗
Impulse propagation in rubber-tube analogues of arterial stenoses and aneurysms.
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Aneurysm↗