Numerical investigation of oxygen mass transfer in a helical-type artery bypass graft

Local oxygen lack in arterial walls (hypoxia) plays a very important role in the initiation, progression and development of intimal hyperplasia (IH) and thrombosis. Aiming to find out whether a helical-type artery bypass graft (ABG) is hypoxia beneficial, a numerical study was carried out to compare oxygen transport between a helical-type ABG and a conventional-type ABG. The dimensionless mass transfer coefficient (Sherwood number) was introduced to evaluate the oxygen mass transfer distribution and detailed oxygen wall flux was computed. The results show that the intrinsic geometry of a helical-type ABG resulted in improved hypoxia and the oxygen-depleted fluid located proximally to the occluded section as compared with that of a conventional-type ABG. However, benefits aside, distinct double low regions (low wall shear stress (WSS) and hypoxia) which might be most prone to IH and more localised and thicker boundary layer of oxygen-depleted fluid were observed at the helical-type ABG. This may explain why the helical flow plays a detrimental role at some locations in the human body. In addition, it was observed that although low WSS region was always accompanied with low oxygen supply, the oxygen transport rate did not adjust simultaneously with flow. The change in oxygen distribution usually lagged behind the flow change. A physiological WSS region may be associated with hypoxia condition. This study captured the qualitative trend of oxygen distribution in ABGs and the effect of helical geometry on reducing hypoxia, which is useful in the structural design of swirling flow vascular devices.     

The influence of out-of-plane geometry on the flow within a distal end-to-side anastomosis

This paper describes a computational and experimental investigation of flow in a proto-type model geometry of a fully occluded 45 deg distal end-to-side anastomosis. Previous investigations have considered a similar configuration where the centerlines of the bypass and host vessels lie within a plane, thereby producing a plane of symmetry within the flow. We have extended these investigations by deforming the bypass vessel out of the plane of symmetry, thereby breaking the symmetry of the flow and producing a nonplanar geometry. Experimental data were obtained using magnetic resonance imaging of flow within perspex models and computational data were obtained from simulations using a high-order spectral/hp element method. We found that the nonplanar three-dimensional flow notably alters the distribution of wall shear stress at the bed of the anastomosis, reducing the peak wall shear stress peak by approximately 10 percent when compared with the planar model. Furthermore, an increase in the absolute flux of velocity into the occluded region, proximal to the anastomosis, of 80 percent was observed in the nonplanar geometry when compared with the planar geometry.     

Experimental evaluation of flow patterns in interposition vein cuff anastomosis. The influence of non-planarity of the inflow

Clinical evidence suggests that the development of myointimal hyperplasia in prosthetic femorodistal bypass grafts may be reduced by the interposition of a cuff of autologous vein between the graft and the recipient artery. Previous experimental work has shown that some of the benefits may be attributed to the geometry of the cuffed anastomosis. Since the distal anastomosis in vivo is often non-planar we have carried out a preliminary study in a model where the graft is at an angle of 45 degrees to the anterior-posterior plane of the anastomosis. This out-of-plane angulation produces highly asymmetric flow patterns in the anastomosis with significant flow separation on the ipsilateral side of the cuff. In the proximal and distal outflow, however, the velocity vectors show significant helical motion with temporal instability in the distal outflow.     

犬不同血管搭桥方法及搭桥血管内流场的计算机数值模拟

目的血管搭桥术后的内膜增生往往导致手术失败,而内膜增生与搭桥血管内的流场密切相关,为改善搭桥血管中的流场结构,作者设计了偏心搭桥手术方法,利用计算机数值模拟技术,探索偏心搭桥和传统搭桥血管中流场的变化,为血管搭桥方法提供优化设计方案。方法16只犬随机分为偏心搭桥组和传统搭桥组进行血管搭桥,测定搭桥前后血管几何数据,搭桥后近心端及远心端吻合口血流量和血压。按测定的血管几何数据,FLUENT 6.2模拟搭桥血管内的流场。结果偏心搭桥近心端和远心端吻合口不在同一平面。传统搭桥中,主体动脉远心端吻合口对应面处存在一个较低壁面剪切应力（WSS）区域及流体停滞点,离脚跟较近的一部分流体会形成涡漩,血流进入主体动脉后,还会表现出迪恩涡二次流;偏心搭桥中,主体动脉吻合口对应面上的低WSS区域和流体停滞点消失,血流接触到吻合口底面后,以切向旋转的方式改变其流动方向,不会形成涡漩,且当血流进入主体动脉后,立即发生螺旋流态且能持续很长一段。结论偏心搭桥能够产生血液旋动流,显著增加远心端血流量、提高WSS。     

An S-type bypass can improve the hemodynamics in the bypassed arteries and suppress intimal hyperplasia along the host artery floor

The development of distal end-to-side anastomotic intimal hyperplasia (IH) has been attributed to the flow disturbance and abnormal wall shear stress (WSS) distribution there. The geometry of the bypass has a strong influence on the flow pattern and WSS distribution. Using a canine model of end-to-side anastomosis, a 45 degrees S-type bypass was compared with 60 degrees , 45 degrees and 30 degrees conventional bypasses in the term of IH along the host artery floor. Numerical blood flow simulations were also carried out to characterize the flow patterns at the distal parts of the bypassed arteries for the 4 models. The results showed that the averaged intima thicknesses of the host artery floors for the 4 bypass models were 119.50+/-10.30 microm (60 degrees ), 65.56+/-6.53 microm (45 degrees ), 45.26+/-5.99 microm (30 degrees ) and 47.64+/-4.85 microm (S-type), respectively, vs. 9.81+/-1.88 microm in the control group (without bypass surgery). Compared with the control group, neointima thickness in all 4 bypass models was significantly increased, but the neointima thickness of the 45 degrees S-type bypass was apparently much better than its 45 degrees conventional counterpart, and was as good as the 30 degrees conventional bypass. The numerical simulation revealed an apparent swirling flow pattern in the S-type bypass, which was very different than the flow patterns in the 3 conventional bypass models. This swirling flow altered the overall flow pattern in the distal part of the bypassed artery and eliminated the low WSS zone along the host artery floor. The improvement in the term of IH for the S-type bypass is most likely due to the alteration of the overall flow pattern and WSS distribution by the geometrical configuration of the S-type bypass.     

Computational model of blood flow in the aorto-coronary bypass graft

Background

Coronary artery bypass grafting surgery is an effective treatment modality for patients with severe coronary artery disease. The conduits used during the surgery include both the arterial and venous conduits. Long- term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded and many of them are diseased. Why do the saphenous vein grafts fail the test of time? Many causes have been proposed for saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non-modifiable causes include different histological structure of the vein compared to artery, size disparity between coronary artery and saphenous vein. However, researches are more interested in the modifiable causes, such as graft flow dynamics and wall shear stress distribution at the anastomotic sites. Formation of intimal hyperplasia at the anastomotic junction has been implicated as the root cause of long- term graft failure.Many researchers have analyzed the complex flow patterns in the distal sapheno-coronary anastomotic region, using various simulated model in an attempt to explain the site of preferential intimal hyperplasia based on the flow disturbances and differential wall stress distribution. In this paper, the geometrical bypass models (aorto-left coronary bypass graft model and aorto-right coronary bypass graft model) are based on real-life situations. In our models, the dimensions of the aorta, saphenous vein and the coronary artery simulate the actual dimensions at surgery. Both the proximal and distal anastomoses are considered at the same time, and we also take into the consideration the cross-sectional shape change of the venous conduit from circular to elliptical. Contrary to previous works, we have carried out computational fluid dynamics (CFD) study in the entire aorta-graft-perfused artery domain. The results reported here focus on (i) the complex flow patterns both at the proximal and distal anastomotic sites, and (ii) the wall shear stress distribution, which is an important factor that contributes to graft patency.

Methods

The three-dimensional coronary bypass models of the aorto-right coronary bypass and the aorto-left coronary bypass systems are constructed using computational fluid-dynamics software (Fluent 6.0.1). To have a better understanding of the flow dynamics at specific time instants of the cardiac cycle, quasi-steady flow simulations are performed, using a finite-volume approach. The data input to the models are the physiological measurements of flow-rates at (i) the aortic entrance, (ii) the ascending aorta, (iii) the left coronary artery, and (iv) the right coronary artery.

Results

The flow field and the wall shear stress are calculated throughout the cycle, but reported in this paper at two different instants of the cardiac cycle, one at the onset of ejection and the other during mid-diastole for both the right and left aorto-coronary bypass graft models. Plots of velocity-vector and the wall shear stress distributions are displayed in the aorto-graft-coronary arterial flow-field domain. We have shown (i) how the blocked coronary artery is being perfused in systole and diastole, (ii) the flow patterns at the two anastomotic junctions, proximal and distal anastomotic sites, and (iii) the shear stress distributions and their associations with arterial disease.

Conclusion

The computed results have revealed that (i) maximum perfusion of the occluded artery occurs during mid-diastole, and (ii) the maximum wall shear-stress variation is observed around the distal anastomotic region. These results can enable the clinicians to have a better understanding of vein graft disease, and hopefully we can offer a solution to alleviate or delay the occurrence of vein graft disease.

     

Nature and distribution of vascular resistance in hypoxic pig lungs

We used the vascular occlusion technique in pig lungs isolated in situ to describe the effects of hypoxia on the distribution of vascular resistance and to determine whether the resistive elements defined by this technique behaved as ohmic or Starling resistors during changes in flow at constant outflow pressure, changes in outflow pressure at constant flow, and reversal of flow. During normoxia, the largest pressure gradient occurred across the middle compliant region of the vasculature (delta Pm). The major effect of hypoxia was to increase delta Pm and the gradient across the relatively noncompliant arterial region (delta Pa). The gradient across the noncompliant venous region (delta Pv) changed only slightly, if at all. Both delta Pa and delta Pv increased with flow but delta Pm decreased. The pressure at the arterial end of the middle region was independent of flow and, when outflow pressure was increased, did not increase until the outflow pressure of the middle region exceeded 8.9 Torr during normoxia and 18.8 Torr during hypoxia. Backward perfusion increased the total pressure gradient across the lung, mainly because of an increase in delta Pm. These results can be explained by a model in which the arterial and venous regions are represented by ohmic resistors and the middle region is represented by a Starling resistor in series and proximal to an ohmic resistor. In terms of this model, hypoxia exerted its major effects by increasing the critical pressure provided by the Starling resistor of the middle region and the ohmic resistance of the arterial region.     

A novel angiotensin II type 1 receptor-associated protein induces cellular hypertrophy in rat vascular smooth muscle and renal proximal tubular cells

Angiotensin II stimulates cellular hypertrophy in cultured vascular smooth muscle and renal proximal tubular cells. This effect is believed to be one of earliest morphological changes of heart and renal failure. However, the precise molecular mechanism involved in angiotensin II-induced hypertrophy is poorly understood. In the present study we report the isolation of a novel angiotensin II type 1 receptor-associated protein. It encodes a 531-amino acid protein. Its mRNA is detected in all human tissues examined but highly expressed in the human kidney, pancreas, heart, and human embryonic kidney cells as well as rat vascular smooth muscle and renal proximal tubular cells. Protein synthesis and relative cell size analyzed by flow cytometry studies indicate that overexpression of the novel angiotensin II type 1 receptor-associated protein induces cellular hypertrophy in cultured rat vascular smooth muscle and renal proximal tubular cells. In contrast, the hypertrophic effects was reversed in renal proximal tubular cell lines expressing the novel gene in the antisense orientation and its dominant negative mutant, which lacks the last 101 amino acids in its carboxyl-terminal tail. The hypertrophic effects are at least in part mediated via protein kinase B activation or cyclin-dependent kinase inhibitor, p27(kip1) protein expression level in vascular smooth muscle, and renal proximal tubular cells. Moreover, angiotensin II could not stimulate cellular hypertrophy in renal proximal tubular cells expressing the novel gene in the antisense orientation and its mutant. These findings may provide new molecular mechanisms to understand hypertrophic agents such as angiotensin II-induced cellular hypertrophy.     

Arterial steal phenomenon in femoro-tibial bypass with arterio-venous shunt

Arterio-venous shunts are sometimes constructed at the distal anastomosis of femoro-tibial bypass grafts in order to increase blood flow velocity within the graft. However, the use of such a shunt may "steal' blood from an already ischaemic distal arterial bed. The aim of this study was to determine the conditions under which this might happen. Experiments were carried out on an in vitro model of the femoro-tibial bypass under steady flow conditions. The simple resistance model of Hyman and Brewer (J. Biomechanics 13, 469-675, 1980), modified to take into account the nonlinear pressure flow relationship through a stenosis, was used to interpret experimental data. Good agreement was obtained between measured and calculated steal.     

Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans.

The main purpose of this study was to find out whether the dominant dorsal lung perfusion while supine changes to a dominant ventral lung perfusion while prone. Regional distribution of pulmonary blood flow was determined in 10 healthy volunteers. The subjects were studied in both prone and supine positions with and without lung distension caused by 10 cmH2O of continuous positive airway pressure (CPAP). Radiolabeled macroaggregates of albumin, rapidly trapped by pulmonary capillaries in proportion to blood flow, were injected intravenously. Tomographic gamma camera examinations (single-photon-emission computed tomography) were performed after injections in the different positions. All data acquisitions were made with the subject in the supine position. CPAP enhanced perfusion differences along the gravitational axis, which was more pronounced in the supine than prone position. Diaphragmatic sections of the lung had a more uniform pulmonary blood flow distribution in the prone than supine position during both normal and CPAP breathing. It was concluded that the dominant dorsal lung perfusion observed when the subjects were supine was not changed into a dominant ventral lung perfusion when the subjects were prone. Lung perfusion was more uniformly distributed in the prone compared with in the supine position, a difference that was more marked during total lung distension (CPAP) than during normal breathing.     

Mass Transger in an Eccentric Annular Region Through Diffusion

The mass transfer in an eccentric annular region through diffusion by taking blood as a Newtonian fluid with the investigation of oxygen transfer and drug transport to the tissue cells in an eccentric catheterized artery is studied. The region bounded by eccentric circles in x-y plane is mapped conformally to concentric circles in \(\xi -\eta\) plane using a conformal mapping \(z = \lambda /1 - \zeta\). The resulting governing equations are analytically solved by using transformation for the concentration. Numerical computations are carried out to understand the simultaneous~effects of absorption parameter and eccentricity on the flow. ~The observation through the numerical computation reveals that, as absorption parameter and eccentricity enhances, the solute concentration diminishes. This mathematical model provides an insight for physiologists to understand the drug transport to the tissues in various clinical treatments of cardiovascular diseases.     

Chromosomal control of chiasma distribution in house mice. Analysis of chiasma distribution in homo- and heterozygotes by inversion in chromosome 1

Examination of chiasma distribution in the chromosome 1 in male mice homo- and heterozygous for distal inversion In(1)12Rk and in normal mice was carried out. No differences in chiasma distribution was found between homozygotes for the inversion and homozygotes for normal chromosome 1. A drastic change in this trait was revealed in heterozygous animals. In heterozygotes, the telomeric segments of SC were asynapsed and unavailable for recombination. This leads to significant decrease in the frequency of bivalents bearing chiasmata in pretelomeric region. In turn, it produced chiasma redistribution in proximal noninverted portion of the bivalent 1. These results could be interpreted as evidence for chromosomal control of chiasma distribution pattern: the distance of certain part of the chromosome from telomere and interference (which also operates at the chromosomal level) are more important for determination of the chiasmata frequency in the given region, than its genetic content.     

Structure and steroidogenic activity of the granulosa layer of F1 preovulatory ovarian follicles of the hen (Gallus domesticus)

The study was performed to determine the structure and steroidogenic activity of granulosa cells derived from the germinal disc region, proximal region and distal region of the largest preovulatory ovarian follicle (F1) of the hen. The study was carried out on 34 Hy-Line Brown egg-laying hens aged 40 weeks. Morphology of the granulosa cells was studied by histological assessment and scanning electron microscopy. Moreover, the level of P4, histochemical activity of 3beta-HSD and expression of 3beta-HSD gene mRNA in granulosa cells of F1 follicle were determined. The findings indicate that the morphology and steroidogenic activity of the granulosa layer in F1 preovulatory ovarian follicle are associated with the region of the follicle. This is consistent with earlier studies. In the germinal disc region the granulosa cells form a multilayer while in the proximal and distal regions granulosa cells form a single layer. Analysis of P4 concentration revealed that its level in granulosa cells was markedly reduced closer to the germinal disc. Moreover, our study demonstrates for the first time the lower histochemical activity of 3beta-HSD and expression of 3beta-HSD mRNA in granulosa cells from the germinal disc region compared with the proximal and distal region.     

Steady flow of couple stress fluid through tubes of slowly varying cross-sections--application to blood flows

Steady laminar flow of a non-Newtonian fluid based on couple stress fluid theory, through narrow tubes of varying cross-sections has been studied theoretically. Asymptotic solutions are obtained for the basic equations and the expressions for the velocity field and the wall shear stress are derived for a general cross-section. Computation and discussions are carried out for the geometries which occur in the context of physiological flows or in particular blood flows. The tapered tubes and constricted tubes are of special importance. It is observed that increase in certain parameters results in erratic flow behaviour proximal to the constricted areas which is further enhanced by the increase in the geometric parameters. This elucidates the implications of the flow in the development of vascular lesions.     

Blood flow and vessel mechanics in a physiologically realistic model of a human carotid arterial bifurcation

The pulsatile flow in an anatomically realistic compliant human carotid bifurcation was simulated numerically. Pressure and mass flow waveforms in the carotid arteries were obtained from an individual subject using non-invasive techniques. The geometry of the computational model was reconstructed from magnetic resonance angiograms. Maps of time-average wall shear stress, contours of velocity in the flow field as well as wall movement and tensile stress on the arterial wall are all presented. Inconsistent with previous findings from idealised geometry models, flow in the carotid sinus is dominated by a strong helical flow accompanied by a single secondary vortex motion. This type of flow is induced primarily by the asymmetry and curvature of the in vivo geometry. Flow simulations have been carried out under the rigid wall assumption and for the compliant wall, respectively. Comparison of the results demonstrates the quantitative influence of the vessel wall motion. Generally there is a reduction in the magnitude of wall shear stress, with its degree depending on location and phase of the cardiac cycle. The region of slow or reversed flow was greater, in both spatial and temporal terms in the compliant model, but the global characteristics of the flow and stress patterns remain unchanged. The analysis of mechanical stresses on the vessel surface shows a complicated stress field. Stress concentration occurs at both the anterior and posterior aspects of the proximal internal bulb. These are also regions of low wall shear stress. The comparison of computed and measured wall movement generally shows good agreement.     

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts remains unquantified in vivo, but is likely to influence flow patterns and haemodynamics, thereby impacting upon graft patency. This study measured the ratio of distal to proximal outflow in 30 patients undergoing infrainguinal bypass for lower limb ischaemia, using a flow probe and a transit-time ultrasonic flow meter. The mean outflow distribution was approximately 75% distal to 25% proximal, with above knee anastomoses having a greater proportion of distal flow (84%) compared to below knee grafts (73%). These in vivo flow characteristics differ significantly from those used in theoretical models studying flow phenomena (50:50 and/or 100:0), and should be incorporated into future research.     

Tracheal compliance and limit flow rate changes in a murine model of asthma

Trachea is the unique passage for air to flow in and out. Its tone is of importance for the respiration system. However, investigation on how tracheal tone changes due to asthma is limited. Aiming at studying how the mechanical property changes due to asthma as well as the compliance and flow limitation, the following methods are adopted. Static and passive pressure-volume tests of rats' trachea of the asthmatic and control groups are carried out and a new type of tube law is formulated to fit the experimental data, based on which changes of compliance and limit flow rate are investigated. In order to give explanation to such changes, histological examinations with tracheal soft tissues are made. The results show that compliance, limit flow rate and material constants included in the tube law largely depend on the longitudinal stretching ratio. Compared with the control group, the tracheal compliance of asthmatic animals decreases significantly, which results in an increased limit flow rate. Histological studies indicate that asthma can lead to hyperplasia/hypertrophy of smooth muscle cells, and increase elastin and collagen fibres in the muscular membrane. Though decreasing compliance increases sta- bility, during the onset of asthma, limit flow rate is much smaller due to the lower transmural pressure. Asthma leads to a stiffer trachea and the obtained results reveal some aspects relevant to asthma-induced tracheal remodelling.     

Helical flow as fluid dynamic signature for atherogenesis risk in aortocoronary bypass. A numeric study

The main purpose of the study was to verify if helical flow, widely observed in several vessels, might be a signature of the blood dynamics of vein graft anastomosis. We investigated the existence of a relationship between helical flow structures and vascular wall indexes of atherogenesis in aortocoronary bypass models with different geometric features. In particular, we checked for the existence of a relationship between the degree of helical motion and the magnitude of oscillating shear stress in conventional hand-sewn proximal anastomosis. The study is based on the numerical evaluation of four bypass geometries that are attached to a simplified computer representation of the ascending aorta with different angulations relative to aortic outflow. The finite volume technique was used to simulate realistic graft fluid dynamics, including aortic compliance and proper aortic and graft flow rates. A quantitative method was applied to evaluate the level of helicity in the flow field associated with the four bypass models under investigation. A linear inverse relationship (R = -0.97) was found between the oscillating shear index and the helical flow index for the models under investigation. The results obtained support the hypothesis that an arrangement of the flow field in helical patterns may elicit damping in wall shear stress temporal gradients at the proximal graft. Accordingly, helical flow might play a significant role in preventing plaque deposition or in tuning the mechanotransduction pathways of cells. Therefore, results confirm that helical flow constitutes an important flow signature in vessels, and its strength as a fluid dynamic index (for instance in combination with magnetic resonance imaging flow visualization techniques) for risk stratification, in the activation of both mechanical and biological pathways leading to fibrointimal hyperplasia.     

Éléments de physiologie et physiopathologie de la microcirculation et de rhéologie. Implications potentielles pour la circulation extracorporelle en chirurgie cardiaque de l’adulte

Cardiopulmonary bypass (CPB) is usually performed by defining therapeutic goals based on macro-hemodynamic parameters such as pump flow, mean arterial blood pressure, haemoglobin concentration or venous line saturation. Nevertheless, oxygen transport to tissues and cells is also dependent on the function of the microcirculation and the rheologic properties of blood. This articles summarizes for clinicians that perform CPB several aspects of physiology and pathophysiology of microcirculation and rheology. Physiological and pathophysiological changes of blood and plasma viscosities, red blood cell aggregation and deformability are explained. Potential clinical implications of changes of blood rheology are discussed.