Pulsatile flow visualization in the abdominal aorta under differing physiologic conditions: implications for increased susceptibility to atherosclerosis.

The infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta.     

Numerical simulation of steady flow fields in a model of abdominal aorta with its peripheral branches

In the present study, a numerical calculation procedure based on a finite volume method was developed to simulate steady flow fields in a model of abdominal aorta with its peripheral branches. The study focused on the steady baseline flow fields and the wall shear stress (WSS) distribution as well as the localization of the reversed flow regions and results were compared to those obtained by other investigators. In the case of resting conditions, the existence of a region of reversed flow of about one to two diameters in size and next to the renal arteries and along the posterior wall as observed by other researchers was confirmed. However, under the exercise conditions this region could be wiped out. The flow reversal along the lateral walls proximal to the bifurcation persisted in both rest and exercise conditions. The WSS distribution and the wall shear stress gradient distribution were obtained. The lowest WSS occurred near the ostia of the renal arteries and the lateral walls of the iliac arteries. And the highest is always at the turn to the branch. The results were generally consistent with those obtained experimentally and numerically by other investigators. It was also shown that the steady flow might be used to depict the averaged behavior of pulsatile flow. The present computer code provides a platform for the future more realistic simulations.     

Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to 31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.     

Experimental determination of velocity profiles and wall shear rate along the rabbit aortoiliac bifurcation: relationship to vessel wall low-density lipoprotein (LDL) metabolism.

We have determined the velocity profiles and wall shear rates along the New Zealand White (NZW) rabbit aortoiliac bifurcation. A pulsatile perfusion apparatus was used to impose physiologic pressure and flow waveforms on nine freshly excised NZW bifurcation segments. Pulsed Doppler velocimetry (PDV) was utilized to construct velocity profiles at five measurement sites: within the infrarenal aorta; immediately distal to the apex of the bifurcation; and, more distally along the iliac arteries. Wall shear rate was derived from a numerical differentiation of the experimental velocity profiles. The results of this study indicate that the average shear rate was lower along the lateral (approximately 40 s-1) vs medial (approximately 240 s-1) wall of the proximal iliac branch. The degree of flow reversal along the proximal lateral walls (20 +/- 2%) exceeded that along the proximal flow divider wall (1 +/- 1%). Flow at the distal iliac measurement sites and within the infrarenal aorta was approximately symmetric. These findings complement our companion in vivo study [Berceli et al., Arteriosclerosis 10, 688-694 (1990)] wherein we determined the rates of low-density lipoprotein (LDL) incorporation and catabolism along this symmetrically bifurcating conduit. Taken together, these studies provide original information regarding the effects of hemodynamics on one presumed atherogenic risk factor, namely, LDL metabolism.     

Unsteady and three-dimensional simulation of blood flow in the human aortic arch

A three-dimensional and pulsatile blood flow in a human aortic arch and its three major branches has been studied numerically for a peak Reynolds number of 2500 and a frequency (or Womersley) parameter of 10. The simulation geometry was derived from the three-dimensional reconstruction of a series of two-dimensional slices obtained in vivo using CAT scan imaging on a human aorta. The numerical simulations were obtained using a projection method, and a finite-volume formulation of the Navier-Stokes equations was used on a system of overset grids. Our results demonstrate that the primary flow velocity is skewed towards the inner aortic wall in the ascending aorta, but this skewness shifts to the outer wall in the descending thoracic aorta. Within the arch branches, the flow velocities were skewed to the distal walls with flow reversal along the proximal walls. Extensive secondary flow motion was observed in the aorta, and the structure of these secondary flows was influenced considerably by the presence of the branches. Within the aorta, wall shear stresses were highly dynamic, but were generally high along the outer wall in the vicinity of the branches and low along the inner wall, particularly in the descending thoracic aorta. Within the branches, the shear stresses were considerably higher along the distal walls than along the proximal walls. Wall pressure was low along the inner aortic wall and high around the branches and along the outer wall in the ascending thoracic aorta. Comparison of our numerical results with the localization of early atherosclerotic lesions broadly suggests preferential development of these lesions in regions of extrema (either maxima or minima) in wall shear stress and pressure.     

Hemodynamics simulation and identification of susceptible sites of atherosclerotic lesion formation in a model abdominal aorta

Employing the rabbit's abdominal aorta as a suitable atherosclerotic model, transient three-dimensional blood flow simulations and monocyte deposition patterns were used to evaluate the following hypotheses: (i) simulation of monocyte transport through a model of the rabbit abdominal aorta yields cell deposition patterns similar to those seen in vivo, and (ii) those deposition patterns are correlated with hemodynamic wall parameters related to atherosclerosis. The deposition pattern traces a helical shape down the aorta with local elevation in monocyte adhesion around vessel branches. The cell deposition pattern was altered by an exercise waveform with fewer cells attaching in the upper abdominal aorta but more attaching around the renal orifices. Monocyte deposition was correlated with the wall shear stress gradient and the wall shear stress angle gradient. The wall stress gradient, the wall shear stress angle gradient and the normalized monocyte deposition fraction were correlated with the distribution of monocytes along the abdominal aorta and monocyte deposition is correlated with the measured distribution of monocytes around the major abdominal branches in the cholesterol-fed rabbit. These results suggest that the transport and deposition pattern of monocytes to arterial endothelium plays a significant role in the localization of lesions.     

Inferior vena caval hemodynamics quantified in vivo at rest and during cycling exercise using magnetic resonance imaging

Compared with the abdominal aorta, the hemodynamic environment in the inferior vena cava (IVC) is not well described. With the use of cine phase-contrast magnetic resonance imaging (MRI) and a custom MRI-compatible cycle in an open magnet, we quantified mean blood flow rate, wall shear stress, and cross-sectional lumen area in 11 young normal subjects at the supraceliac and infrarenal levels of the aorta and IVC at rest and during dynamic cycling exercise. Similar to the aorta, the IVC experienced significant increases in blood flow and wall shear stress as a result of exercise, with greater increases in the infrarenal level compared with the supraceliac level. At the infrarenal level during resting conditions, the IVC experienced higher mean flow rate than the aorta (1.2 +/- 0.5 vs. 0.9 +/- 0.4 l/min, P < 0.01) and higher mean wall shear stress than the aorta (2.0 +/- 0.6 vs. 1.3 +/- 0.6 dyn/cm(2), P < 0.005). During exercise, wall shear stress remained higher in the IVC compared with the aorta, although not significantly. It was also observed that, whereas the aorta tapers inferiorly, the IVC tapers superiorly from the infrarenal to the supraceliac location. The hemodynamic and anatomic data of the IVC acquired in this study add to our understanding of the venous circulation and may be useful in a clinical setting.     

Flow patterns at the major T-junctions of the dog descending aorta

Using a novel technique developed in our own laboratory, an isolated transparent arterial segment containing the whole descending aorta and its four major branches was prepared from a dog. The flow patterns at each aortic T-junction were studied in detail under the conditions of steady flow by means of flow visualization and cinemicrographic techniques. It was found that a standing recirculation zone consisting of a pair of thin-layered spiral secondary flows located symmetrically about the common median plane of the aorta and side branches was formed at each T-junction over a wide range of flow conditions including the time-averaged estimated mean values of physiological flow rates and flow rate ratios. The results support the recent in vivo findings by other investigators that flow reversal occurs at some junctions of the dog abdominal aorta during each cardiac cycle. The flow patterns at the aortic T-junctions were very much similar to those previously observed in various glass model T-junctions. However, due to the particular anatomical structure of the vessel wall at each branching site (the curvature of the wall was very sharp at the flow divider, but gently rounded at the bend opposite to it) no recirculation zone was formed in the side branches. At a given flow rate ratio, the measured critical Reynolds numbers for the formation of spiral secondary flows and fully developed disturbed flows were much higher in aortic T-junctions than those in glass model T-junctions having equivalent branching angles and diameter ratios. These results indicate that, in the circulation, conditions at arterial T-junctions appear to be optimal for minimizing the formation of disturbed flows.     

Velocity distribution along an elastic model of human arterial tree

An experimental investigation of an elastic model of the human arterial tree, has been performed for physiological type flow by pulsed Doppler ultrasonic velocimetry. The arterial tree model, fabricated in clear polyurethane, includes the aortic arch, with a Starr-Edwards ball valve mounted in the root of the aorta, the descending aorta and the iliac bifurcation. Our study showed that the velocity profile, a few centimeters beyond the valve, is skewed, with higher velocities towards the top and the inner wall (anatomically the posterior and left lateral wall). An inward shift of the maximum velocity and reverse flow are denoted along the inner wall of the aortic arch. The velocity profiles in the descending aorta are blunted. Downstream from the vertex of the iliac bifurcation, there is vorticity creation, but the branching effect is quickly damped by the pulsatility of the flow and the elasticity of the wall.     

Numerical study on the effect of secondary flow in the human aorta on local shear stresses in abdominal aortic branches

Flow in the aortic arch is characterized primarily by the presence of a strong secondary flow superimposed over the axial flow, skewed axial velocity profiles and diastolic flow reversals. A significant amount of helical flow has also been observed in the descending aorta of humans and in models. In this study a computational model of the abdominal aorta complete with two sets of outflow arteries was adapted for three-dimensional steady flow simulations. The flow through the model was predicted using the Navier-Stokes equations to study the effect that a rotational component of flow has on the general flow dynamics in this vascular segment. The helical velocity profile introduced at the inlet was developed from magnetic resonance velocity mappings taken from a plane transaxial to the aortic arch. Results showed that flow division ratios increased in the first set of branches and decreased in the second set with the addition of rotational flow. Shear stress varied in magnitude with the addition of rotational flow, but the shear stress distribution did not change. No regions of flow separation were observed in the iliac arteries for either case. Helical flow may have a stabilizing effect on the flow patterns in branches in general, as evidenced by the decreased difference in shear stress between the inner and outer walls in the iliac arteries.     

Recirculation zone length in renal artery is affected by flow spirality and renal-to-aorta flow ratio

Haemodynamic perturbations such as flow recirculation zones play a key role in progression and development of renal artery stenosis, which typically originate at the aorta-renal bifurcation. The spiral nature of aortic blood flow, division of aortic blood flow in renal artery as well as the exercise conditions have been shown to alter the haemodynamics in both positive and negative ways. This study focuses on the combinative effects of spiral component of blood flow, renal-to-aorta flow ratio and the exercise conditions on the size and distribution of recirculation zones in renal branches using computational fluid dynamics technique. Our findings show that the recirculation length was longest when the renal-to-aorta flow ratio was smallest. Spiral flow and exercise conditions were found to be effective in reducing the recirculation length in particular in small renal-to-aorta flow ratios. These results support the hypothesis that in renal arteries with small flow ratios where a stenosis is already developed an artificially induced spiral flow within the aorta may decelerate the progression of stenosis and thereby help preserve kidney function.     

Fractal network model for simulating abdominal and lower extremity blood flow during resting and exercise conditions

We present a one-dimensional (1D) fluid dynamic model that can predict blood flow and blood pressure during exercise using data collected at rest. To facilitate accurate prediction of blood flow, we developed an impedance boundary condition using morphologically derived structured trees. Our model was validated by computing blood flow through a model of large arteries extending from the thoracic aorta to the profunda arteries. The computed flow was compared against measured flow in the infrarenal (IR) aorta at rest and during exercise. Phase contrast-magnetic resonance imaging (PC-MRI) data was collected from 11 healthy volunteers at rest and during steady exercise. For each subject, an allometrically-scaled geometry of the large vessels was created. This geometry extends from the thoracic aorta to the femoral arteries and includes the celiac, superior mesenteric, renal, inferior mesenteric, internal iliac and profunda arteries. During rest, flow was simulated using measured supraceliac (SC) flow at the inlet and a uniform set of impedance boundary conditions at the 11 outlets. To simulate exercise, boundary conditions were modified. Inflow data collected during steady exercise was specified at the inlet and the outlet boundaries were adjusted as follows. The geometry of the structured trees used to compute impedance was scaled to simulate the effective change in the cross-sectional area of resistance vessels and capillaries due to exercise. The resulting computed flow through the IR aorta was compared to measured flow. This method produces good results with a mean difference between paired data to be 1.1 +/- 7 cm(3) s(- 1) at rest and 4.0 +/- 15 cm(3) s(- 1) at exercise. While future work will improve on these results, this method provides groundwork with which to predict the flow distributions in a network due to physiologic regulation.     

多重干预RAAS对大鼠慢性心功能不全心室重构及血钾的影响

目的探讨多重干预RAAS对大鼠慢性心功能不全心室重构及血钾的影响。方法实验采用缩窄大鼠腹主动脉法建立慢性压力负荷致心功能不全动物模型,选6周龄20只雌性SD大鼠,随机分4组(每组5只),B组(手术模型组)、C组(卡托普利组)、D组(卡托普利+缬沙坦组)、E组(卡托普利+缬沙坦+螺内酯组),另随机抽取5只同龄雌性SD大鼠假手术作为对照(A组)。给药8周后用Doppler超声心动图检测大鼠心脏结构和心功能各项参数的变化,放射免疫法测定血浆AngⅡ,ALDO浓度,并生化检测血钾水平。结果腹主动脉结扎后第9周,与A组比较,B组舒张末期室间隔厚度(IVSTD)、舒张末期左室后壁厚度(LVPWTD)、相对室壁厚度(RWT)、左室重量(LVM)、左室重量与体重比(LVM/BW)均显著提高(P<0.05);C、D、E组与B组相比,LVM,LVM/BW下降显著(P<0.05)。各药物干预组(C、D、E)血浆AngⅡ,ALDO水平明显低于B组(P<0.05),以联合应用螺内酯组明显。各药物干预组与A组和B组相比较,血钾水平差异无显著性(P>0.05)。结论联合应用卡托普利、缬沙坦及螺内酯多重干预RAAS能明显改善大鼠慢性心功能不全心室重构,对血钾无明显影响。     

Vessel Dimensions in Premature Atheromatous Disease of Aortic Bifurcation

The area ratio of the abdominal aortic bifurcation is defined as the ratio of the sum of the cross-sectional areas of the common iliac arteries to the cross-sectional area of the aorta. Abnormality of the area ratio is associated with initiation of atheroma of the lower aorta. Hypoplasia of the abdominal aorta predisposes to early occlusion as the atheromatous process advances.In five out of six women with thrombosis at the aortic bifurcation the area ratio was low. Hypoplasia of the abdominal aorta was present in two of these patients. All six patients were successfully treated by aortoiliac disobliteration and reconstruction.     

Coupling between MRI-assessed regional aortic pulse wave velocity and diameters in patients with thoracic aortic aneurysm: a feasibility study

Aims

Thoracic aortic aneurysm (TAA) is potentially life-threatening and requires close follow-up to prevent aortic dissection. Aortic stiffness and size are considered to be coupled. Regional aortic stiffness in patients with TAA is unknown. We aimed to evaluate coupling between regional pulse wave velocity (PWV), a marker of vascular stiffness, and aortic diameter in TAA patients.

Methods

In 40 TAA patients (59 ± 13 years, 28 male), regional aortic diameters and regional PWV were assessed by 1.5 T MRI. The incidence of increased diameter and PWV were determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta; S4, suprarenal and S5, infrarenal abdominal aorta). In addition, coupling between regional PWV testing and aortic dilatation was evaluated and specificity and sensitivity were assessed.

Results

Aortic diameter was 44 ± 5 mm for the aortic root and 39 ± 5 mm for the ascending aorta. PWV was increased in 36 (19 %) aortic segments. Aortic diameter was increased in 28 (14 %) segments. Specificity of regional PWV testing for the prediction of increased regional diameter was ≥ 84 % in the descending thoracic to abdominal aorta and ≥ 68 % in the ascending aorta and aortic arch.

Conclusion

Normal regional PWV is related to absence of increased diameter, with high specificity in the descending thoracic to abdominal aorta and moderate results in the ascending aorta and aortic arch.     

Cardiovascular response to lower body negative pressure before and after 20 days horizontal bed rest

To evaluate the effects of 20 days bed rest (BR) on cardiovascular system in normal subjects, left ventricular (LV) echocardiography and vascular ultrasound of the common carotid artery and abdominal aorta were performed during rest and a supine lower body negative pressure (LBNP) test in 14 healthy volunteers (mean age: 22 years) before and after BR. After BR, heart rates (HR) at rest and during LBNP (-40 mmHg) increased. In contrast, LV dimensions, stroke volume, and blood pressures decreased both at rest and during LBNP. Also LBNP tolerance time decreased after BR. Although resting cardiac output (CO) and abdominal aortic flow decreased after bed rest, CO and abdominal aortic flow were unchanged during LBNP comparing before and after BR. Common carotid artery flows both at rest and during LBNP showed no change after BR. LBNP did not increase HR before BR, but increased HR prominently after BR. In conclusion, LBNP tolerance time and LV size during LBNP decreased after BR, suggesting orthostatic intolerance due to a decreased blood volume. However, CO and flow in the abdominal aorta and common carotid artery during LBNP were similar before and after BR due to a compensatory increase after BR.     

Flow behaviour in an asymmetric compliant experimental model for abdominal aortic aneurysm

An experimental study was carried out on asymmetrical abdominal aortic aneurysm (AAA) to analyse the physiological flows involved. Velocity measurements were performed using particle image velocimetry. Resting and exercise flow rates were investigated in models with rigid and compliant walls to assess the parameters affecting the flow behaviour. The secondary flow patterns, and especially the evolution of the vortices within the AAA, were found to be highly dependent on both the flow waveforms and the wall behaviour. Vortices impacts on the distal walls of the AAA occur in the compliant model and can increase the local pressure on the AAA walls and thus increase the wall stresses; AAA wall stresses are one of the most important factors contributing to ruptured aneurysm.     

Inhibited aortic aneurysm formation in BLT1-deficient mice

Leukotriene B(4) is a proinflammatory lipid mediator generated by the enzymes 5-lipoxygenase and leukotriene A(4) hydrolase. Leukotriene B(4) signals primarily through its high-affinity G protein-coupled receptor, BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. In this study, we tested the hypothesis that BLT1 is necessary for abdominal aortic aneurysm (AAA) formation, a major complication of atherosclerotic vascular disease. Chow-fed Apoe(-/-) and Apoe(-/-)/Blt1(-/-) mice were treated with a 4-wk infusion of angiotensin II (1000 ng/min/kg) beginning at 20 wk of age, in a well-established murine AAA model. We found a reduced incidence of AAA formation as well as concordant reductions in the maximum suprarenal/infrarenal diameter and total suprarenal/infrarenal area in the angiotensin II-treated Apoe(-/-)/Blt1(-/-) mice as compared with the Apoe(-/-) controls. Diminished AAA formation in BLT1-deficient mice was associated with significant reductions in mononuclear cell chemoattractants and leukocyte accumulation in the vessel wall, as well as striking reductions in the production of matrix metalloproteinases-2 and -9. Thus, we have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice and that BLT1 deletion in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity. These findings extend the role of BLT1 to a critical complication of vascular disease and underscore its potential as a target for intervention in modulating multiple pathologies related to atherosclerosis.     

Topographical mapping of sites of enhanced HRP permeability in the normal rabbit aorta.

The spatial distribution of sites of enhanced permeability to the macromolecule horseradish peroxidase (HRP) in the normal rabbit aorta after one min circulation was studied using image analysis. These sites, referred to as "HRP spots," exhibit a nonuniform distribution that is qualitatively similar in all rabbits studied. The density of HRP spots is highest in the aortic arch, decreases distally, reaches a minimum in the lower descending thoracic aorta, and then increases again in the abdominal aorta. The region of highest spot density follows a clockwise helical pattern in the aortic arch and outside the arch occurs in streaks largely oriented in the bulk flow direction. The streaks in the abdominal aorta localize along the anatomical right lateral wall and occasionally along the left lateral wall proximal to the celiac artery and along the ventral wall between the celiac and superior mesenteric arteries. The density of spots is high in the immediate vicinity of aortic ostia with the most elevated density being distal to ostia in most cases. At a short distance from the ostium edge of the celiac and superior mesenteric branches the proximal density is comparably high, and no preferred spot orientation is observed around the brachiocephalic vessel. These results are consistent with an influence of localizing factors such as detailed hemodynamic phenomena and/or arterial wall structural and/or functional variations.     

Finite element models of total shoulder replacement: Application of boundary conditions

We present a one-dimensional (1D) fluid dynamic model that can predict blood flow and blood pressure during exercise using data collected at rest. To facilitate accurate prediction of blood flow, we developed an impedance boundary condition using morphologically derived structured trees. Our model was validated by computing blood flow through a model of large arteries extending from the thoracic aorta to the profunda arteries. The computed flow was compared against measured flow in the infrarenal (IR) aorta at rest and during exercise. Phase contrast-magnetic resonance imaging (PC-MRI) data was collected from 11 healthy volunteers at rest and during steady exercise. For each subject, an allometrically-scaled geometry of the large vessels was created. This geometry extends from the thoracic aorta to the femoral arteries and includes the celiac, superior mesenteric, renal, inferior mesenteric, internal iliac and profunda arteries. During rest, flow was simulated using measured supraceliac (SC) flow at the inlet and a uniform set of impedance boundary conditions at the 11 outlets. To simulate exercise, boundary conditions were modified. Inflow data collected during steady exercise was specified at the inlet and the outlet boundaries were adjusted as follows. The geometry of the structured trees used to compute impedance was scaled to simulate the effective change in the cross-sectional area of resistance vessels and capillaries due to exercise. The resulting computed flow through the IR aorta was compared to measured flow. This method produces good results with a mean difference between paired data to be 1.1 ± 7 cm³ s^? 1 at rest and 4.0 ± 15 cm³ s^? 1 at exercise. While future work will improve on these results, this method provides groundwork with which to predict the flow distributions in a network due to physiologic regulation.