Mechanical behavior of pressurized in vitro prearteriolar vessels determined with a video system

The muscular resistance arteries of the mesentery and brain serve two different control functions in the cardiovascular system. The former are representative vessels of vascular beds that influence total peripheral resistance and blood pressure; the latter are a good model of vessels in beds that demonstrate blood flow autoregulation. Our purpose was to develop a versatile myographic system appropriate for the in vitro study of 75–250 μm diameter vessels and to explore different physiological properties of cerebral and mesenteric arteries. In this paper the system is described in detail, examples of its use in determining the dynamic responses of the vessels to electrical stimulation are provided, and certain measures indicative of the extent of myogenic behavior are characterized. Cylindrical artery segments about 3-mm long were dissected from Wistar-Kyoto rats and mounted in a chamber filled with physiological saline solution maintained at 37°C. The same solution was perfused via a syringe into one end of the vessel through a microcannula. The other end was then occluded so that experiments could be made over a wide range of transmural pressures without flow. The vessel was viewed through a microscope coupled with a TV camera, and the video output signal of a selected scan line was processed by an electronic dimension analyzing system. This permitted simultaneous digital presentation and analog voltage outputs of the vessel wall thicknesses and lumen diameter. We further incorporated servo control of the syringe using a motor drive. In this way, vessel tests could be carried out at constant pressure or constant diameter, and vessel responses could be obtained following either pressure or diameter command signals. Using the methods presented in this study, small vessels can be maintained under conditions that approximate their in vivo state more closely than other in vitro techniques using ring segments on wires. We also find that the opto-electronic instrumentation is ideally suited for studying the dynamic vessel properties that underlie the control of vascular smooth muscle.     

Numerical comparison of hemodynamics with atrium to aorta and ventricular apex to aorta VAD support

We report the first attempt to study with numerical methods ventricular assist device (VAD) models and the effects of various inlet VAD cannulations, coupling physical explanations and numerical investigation conclusions with clinical research results. We compared the hemodynamic response with VAD support by using two distinct VAD-inlet cannulation configurations: left atrium to aorta and left ventricular apex to aorta. Impeller pump and displacement pump VADs are considered. Constant VAD flow rate and counterpulsation motion models are simulated. The native cardiovascular system is modeled using the concentrated-parameter method by considering the flow resistance, vessel elasticity, and inertial effect of blood flow in cardiovascular system individual segments. Impeller and displacement pump dynamic models are represented by corresponding inlet and outlet flow rate changes in the VADs. Results show that the two VAD inlet cannulation configurations produce similar cardiac response (flows, pressures, volumes), except that when the VAD flow approaches the 100% assisting condition, the peak left ventricular systolic pressure and diastolic volume increase slightly in the left atrial cannulation, whereas they drop markedly in the left ventricular apex cannulation, suggesting increased ventricular wall tension and ventricular dilatation in the left atrial cannulation and that hemodynamically the left ventricular apex cannulation is more advantageous.     

Importance of collateral vessels in aortic coarctation: computer simulation at rest and exercise using transmission line elements

Coarctation of the aorta causes arterial hypertension in the upper body and a low blood pressure downstream. Collateral blood vessels compensate by reducing the downstream pressure drop. To study the effect of various coarctation and collateral properties, we designed a computer model of the arterial circulation. The model contains a flow source and a library of subroutines for the lines and connectors. Distributed friction and wall viscoelasticity effects are included. Computer simulation was performed, using published values for vessel dimensions, in an arterial model with a coarctation and one lumped collateral. Rest and two levels of exercise (by increased heart rate) were studied. Without a collateral, we found the downstream pressure of the model was extremely dependent on the size of the coarctation. A collateral vessel reduced the pressure difference between the up- and downstream circulations. For a severe coarctation, the length and the diameter of the collateral were the main factors determining the downstream pressure and flow, whereas wall stiffness of the collateral had little influence. The relationship between mean pressure drop and cardiac output in coarctation was also dependent on the peripheral resistance in different flow beds, especially during exercise.     

Importance of collateral vessels in aortic coarctation: computer simulation at rest and exercise using transmission line elements

Coarctation of the aorta causes arterial hypertension in the upper body and a low blood pressure downstream. Collateral blood vessels compensate by reducing the downstream pressure drop. To study the effect of various coarctation and collateral properties, we designed a computer model of the arterial circulation. The model contains a flow source and a library of subroutines for the lines and connectors. Distributed friction and wall viscoelasticity effects are included. Computer simulation was performed, using published values for vessel dimensions, in an arterial model with a coarctation and one lumped collateral. Rest and two levels of exercise (by increased heart rate) were studied. Without a collateral, we found the downstream pressure of the model was extremely dependent on the size of the coarctation. A collateral vessel reduced the pressure difference between the up- and downstream circulations. For a severe coarctation, the length and the diameter of the collateral were the main factors determining the downstream pressure and flow, whereas wall stiffness of the collateral had little influence. The relationship between mean pressure drop and cardiac output in coarctation was also dependent on the peripheral resistance in different flow beds, especially during exercise.     

Coupled fluid-wall modelling of steady flow in stenotic carotid arteries

Arterial stenoses may cause critical blood flow and wall conditions leading to clinical complications. In this paper computational models of stenotic carotid arteries are proposed and the vessel wall collapse phenomenon is studied. The models are based on fluid-structure interactions (FSI) between blood and the arterial walls. Coupled finite element and computational fluid dynamics methods are used to simultaneously solve for stress and displacement in the solid, and for pressure, velocity and shear stress in the fluid domain. Results show high wall shear stress at the stenosis throat and low (negative) values accompanied by disturbed flow patterns downstream of the stenosis. The wall circumferential stress varies abruptly from tensile to compressive along the stenosis with high stress concentration on the plaque shoulders showing regions of possible plaque rupture. Wall compression and collapse are observed for severe cases. Post-stenotic collapse of the arterial wall occurs for stenotic severity as low as 50%, with the assumption that a given amount of blood flow needs to pass the stenotic artery; whereas if constant pressure drop should be maintained across a constriction, then collapse happens at severity of 75% and above. The former assumption is based on the requirement of adequate blood supply to the downstream organs/tissue, while the latter stems from the fact that the pumping mechanism of the body has a limited capacity in regulating blood pressure, in case a stenosis appears in the vasculature.     

Incorporating vessel taper and compliance properties in Navier-Stokes based blood flow models

A popular and useful technique used to model blood flow in cardiovascular simulations is to divide each blood vessel into a series of segments, each with its own lumped resistance, intertance, and compliance parameters. The values of these parameters are usually obtained through a simplification of the Navier-Stokes equations for fluid flow. However, the simplification often ignores the nonlinear and convective terms of the equations, resulting in errors in the parameter values, especially in the value found for resistance per unit length. We report a new method for the calculation of vessel resistance per unit length which takes into account the effects of vessel taper and wall compliance. It is shown that these effects can be addressed by the addition of two time-varying terms to the calculation of resistance per unit length. One term, due to vessel taper, is proportional to volumetric flow rateQ. The other term, due to vessel compliance, is proportional to ∂p/∂t. These variables are readily available in computer simulations of blood flow in lumped parameter systems. Using data for the descending aorta, the new parameter values, when averaged over a cardiac cycle, compare favorably with results in the literature.     

兔腹主动脉狭窄后剪切力的变化对局部内皮细胞形态和通透性的影响

兔腹主动脉狭窄至正常的55.2％，伊文思蓝对动脉染色，在扫描电镜下观察内皮细胞形态，计算细胞形态指数。动脉狭窄血管内流动壁面剪切率的分布由计算机数值模拟确定。结果表明，在紧接狭窄处的近远两侧，血流受到严重干扰，内皮细胞的形态和对伊文思蓝白蛋白复合物通透性发生明显改变。研究表明，这些改变不但与剪切应力的大小有关，还与血液流动的状态有关。这与动脉粥样硬化一般好发于血液流动受到干扰，流动发生分离区域的解剖观察一致。     

Computational analysis of the effect of the control model of intraaorta pump on ventricular unloading and vessel response

The intraaorta pump is a novel left ventricular assist device (LVAD) whose hemodynamic effects on the circulatory system is unknown. This article aims to evaluate the different effects on the circulatory system supported by the intraaorta pump. In this article, the pump is controlled by three control strategies, including the continuous flow method, the constant rotational speed, and the constant pressure head. A cardiovascular pump system, which includes cardiovascular circulation, intraaorta pump, and regulating mechanisms of systemic circulation, has been proposed. Left ventricle pressure (LVP), end-diastolic volume (EDV), and left ventricular external work (LVEW) were used to evaluate the degree of ventricular unloading. The pulsatile index (PI), which is defined as a ratio of pulse pressure and mean arterial pressure (MAP), was used to evaluate the effect of the vessel response by three control strategies. The comparison results showed that LVP and EDV were lower than those measured before the intraaorta pump was implanted. For LVEW, the constant pressure head strategy provided a superior ventricular unloading compared with other strategies. Support of the pump led to the lower pulsatility by the three models. However, the PI of the constant pressure head was the most at 0.37. In conclusion, these results indicate that the intraaorta pump controlled by constant pressure head strategy provides superior ventricular unloading and pulsatility of the vessel.     

Increase in the calculated resistance of anatomically fixed stenosis in vitro in association with decrease in distal resistance

The effects of changes in distal resistance on stenotic resistance were studied in vitro. Physiological saline was passed through the left carotid artery obtained from the dog, flexible rubber tubing, or through solid polyethylene tubing with a constant perfusion pressure or with a constant flow rate. Various stenotic resistances were established using a screw type constrictor and the distal resistance was varied by allowing physiological saline to pass through either a 23 gauge hypodermic needle (high peripheral resistance) or 23 and 20 gauge needles (low peripheral resistance ). For arteries with anatomically fixed stenosis, the calculated resistance was increased in association with reduction of the distal resistance. The stenotic resistance in the flexible rubber tubing changed in the same manner as that of the carotid artery, while the solid polyethylene tubing showed no significant stenotic resistance changes due to altering the distal resistance. These findings suggest that the stenotic resistance change of the artery correlates with the elasticity of the vessel wall and also indicate that resistance values were of little usefulness for evaluating the effects of vasodilating stimuli on the vessel segment with a significant stenosis.     

Haemodynamic model of a unilateral iliac stenosis with an aortoiliac bypass

A hydrodynamic model for the part of the human arterial network below the renal arteries has been constructed using specially fabricated distensible tubes and a pulsatile pump to simulate an aortoiliac bypass. The experiments and the computer model indicated that no ‘steal’ occurred due to the insertion of the bypass graft. Also, the results showed that the length of the stenosis had a non-systematic apparent effect on the physiological significance of the obstruction and that the kinetic power represented only a small percentage of the total power. The total power efficiency of the bypass graft was unaffected by its elastic properties. The experimental investigation also indicated that the pressure drop across the stenosis was considerably larger than the drop calculated using the Poiseuille flow relationship when the stenosis was severe. Therefore, a critical arterial stenosis value cannot be defined as an obstruction of a constant percentage reduction of luminal area. It varies directly with the effective cross-sectional area and inversely with the flow rate. The value of angiography in assessing the functional significance of any arterial stenosis is there-fore limited. A better method for evaluation requires quantitative measurements of local blood pressure and blood flow, not only at rest, but also under conditions creating augmented flows due to exercise.     

Effects of lower-body negative pressure on blood flow with applications to the human cardiovascular system

The paper reports a theoretical investigation into the effects of lower-body negative pressure on blood flow through the human cardiovascular system. The human cardiovascular system is modelled as a closed network of arteries, arterioles, capillaries, venules and veins of different lengths and cross-sections. The pumping action is provided by the contraction of the ventricles. The model has been analysed using the finite-element method. The pertinent equations incorporating the effects of lower-body negative pressure for the pressures and flow velocities have been derived, and the quantitative results have been computed. Percentage changes in flow velocities, pressure drops and conductances under the application of lower-body negative pressure in the various segments and organs of the entire cardiovascular system are obtained. The lower-body negative pressure has no effect on the flow rates in carotid, ulnar and coronary arteries, nor on the supply of blood to the upper extremities, kidneys, spleen and liver. The major effects are found in the lower extremities.     

Mean systemic filling pressure as a characteristic pressure for venous return

Guyton's theory on venous return, implying a linear relationship between blood flow and central venous pressure, was tested in an intact circulation after thoracotomy and airtight chest closure. In eleven Yorkshire pigs (approx. 10 kg) we measured flow in the pulmonary artery and aorta and pressure in the central veins and aorta during pentobarbital anesthesia and mechanical ventilation. To change central venous pressure different lung volumes were randomly applied at intervals of 5 min in a series of inspiratory hold procedures of 7.2 s. During these short periods hemodynamic steady state circumstances were met without involvement of cardiovascular control mechanisms.We confirmed the linear relationship between venous return and central venous pressure and derived mean systemic filling pressure from the regression equation. Mean systemic filling pressure was on average 10.5±2.3 (SD) mm Hg.The time dependent changes during the inspiratory hold procedure showed that the increase in central venous pressure was the primarily dependent variable, followed by a decrease in venous return and right ventricular output. After a delay of 2–4 heart beats also a decrease in left ventricular output and aortic pressure occurred. Subsequently, the lower venous return during inspiratory hold was mainly sustained by the lower aortic pressure, but nevertheless fulfilled the linear relationship mentioned above.For analysis of flow and pressure changes in the systemic circulation during changes of central venous pressure a tube of constant flow resistance was used as a conceptual model. Consequently, the point where mean systemic filling pressure exists during normal flow conditions was predicted at a characteristic location in the peripheral venous system. Downstream from this point blood pressure will rise and vessel capacity will be filled up during increases in central emptying vessel capacity partially.     

Haemodynamic responses and renin release during stimulation of afferent renal nerves in the cat.

1. Experiments were done on anaesthetized cats to study the effect of electrical stimulation of afferent renal nerves on the circulatory system and on the release of renin from the kidney. 2. Stimulation of afferent renal nerves over a wide range of parameters consistently elicited an increase in arterial pressure and heart rate. This response was still present in paralysed animals and was not accompanied by changes in respiration or in sympathetic autonomic activity usually associated with painful stimulation. Mesenteric and iliac vasoconstriction was observed concomitantly with the increase in arterial pressure. 3. Release of renin from the contralateral innervated kidney was not significantly changed by stimulation of afferent renal nerves. 4. The existence of renal vascular mechanoreceptors was investigated by altering renal circulation. Stenosis of the renal artery or a marked reduction in renal perfusion pressure elicited an increase in arterial pressure while stenosis of the renal vein elicited a decrease in arterial pressure. These responses, however, were not affected by denervation of the kidney and were therefore interpreted as not being due to neural mechanisms. 5. The precise nature, location and physiological role of renal receptors involved in the cardiovascular responses observed during electrical stimulation of afferent renal nerves remain to be determined.     

Coarctation of the aorta—a theoretical and experimental analysis of the effects of a centrally located arterial stenosis

Aortic coarctation is a local constriction of the aorta that may severely affect haemodynamics. It is therefore important to quantify these effects. Using Bernoulli's equation and the momentum theorem, the pressure drop is described including the pressure recovery distal to the coarctation and the effects of collateral flow; both laminar and turbulent. Assuming the coarctation and collaterals to be stiff, a quadratic relationship between flow and pressure drop is expected for flow through the coarctation and for turbulent collateral flow. For laminar collateral flow, a linear relationship is expected. The coarctation flow was studied in a model consisting of a rigid tube with local constriction, connected to a flooded-level tank, containing a 36 per cent by weight solution of sucrose, with a viscosity equivalent to that of blood at body temperature. The pressure drop across the constriction showed a quadratic relationship to flow in agreement with theoretical expectations. Pressure recovery in this model was very slight (0–4 mm Hg). Nine patients with aortic coarctation were catheterised. Cardiac output and pressure drop across the coarctation were measured at rest and during supine cycle exercise at two different workloads. The relationship between mean pressure drop and cardiac output tended to be either ‘parabolic’ or, in some cases, approximately linear, suggesting that the flow situation in aortic coarctation can be quantified by expressions that either linearly or quadratically relate pressure and flow.     

Effect of Stenosis Asymmetry on Blood Flow and Artery Compression: A Three-Dimensional Fluid-Structure Interaction Model

A nonlinear three-dimensional thick-wall model with fluid-structure interactions is introduced to simulate blood flow in carotid arteries with an asymmetric stenosis to quantify the effects of stenosis severity, eccentricity, and pressure conditions on blood flow and artery compression (compressive stress in the wall). Mechanical properties of the tube wall are measured using a thick-wall stenosis model made of polyvinyl alcohal hydrogel whose mechanical properties are close to that of carotid arteries. A hyperelastic Mooney–Rivlin model is used to implement the experimentally measured nonlinear elastic properties of the tube wall. A 36.5% pre-axial stretch is applied to make the simulation physiological. The Navier–Stokes equations in curvilinear form are used for the fluid model. Our results indicate that severe stenosis causes critical flow conditions, high tensile stress, and considerable compressive stress in the stenosis plaque which may be related to artery compression and plaque cap rupture. Stenosis asymmetry leads to higher artery compression, higher shear stress and a larger flow separation region. Computational results are verified by available experimental data. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8710+e     

Hemodynamic effects of sildenafil in men with severe coronary artery disease

BACKGROUND: The cardiovascular effects of sildenafil are important because of the frequent presence of underlying cardiac disease in men with erectile dysfunction and reports indicating serious cardiac events temporally associated with the use of this drug. METHODS: We assessed the systemic, pulmonary, and coronary hemodynamic effects of oral sildenafil (100 mg) in 14 men (mean [+/-SD] age, 61+/-11 years) with severe stenosis of at least one coronary artery (stenosis of >70 percent of the vessel diameter) who were scheduled to undergo percutaneous coronary revascularization. Blood-flow velocity and flow reserve were assessed with a Doppler guidewire in 25 coronary arteries, including 13 severely diseased arteries (mean stenosis, 78+/-7 percent) and 12 arteries without stenosis, used as a reference; maximal hyperemia was induced (to assess flow reserve) with the intracoronary administration of adenosine both before and after sildenafil. RESULTS: Oral sildenafil produced only small decreases (<10 percent) in systemic arterial and pulmonary arterial pressures, and it had no effect on pulmonary-capillary wedge pressure, right atrial pressure, heart rate, or cardiac output. There were no significant changes in average peak coronary flow velocity, coronary-artery diameter, volumetric coronary blood flow, or coronary vascular resistance. Coronary flow reserve at base line was lower in the stenosed arteries (1.26+/-0.26) than in the reference arteries (2.19+/-0.44) and increased about 13 percent in both groups of arteries combined after the administration of sildenafil (from 1.70+/-0.59 to 1.92+/-0.72, P=0.003). The ratio of coronary flow reserve in coronary arteries with stenosis to that in the reference arteries (0.57+/-0.14) was not affected by sildenafil. CONCLUSIONS: No adverse cardiovascular effects of oral sildenafil were detected in men with severe coronary artery disease.     

颈内动脉狭窄对体循环系统影响的集中参数模型研究

研究颈内动脉病变时对整个颈动脉系统的影响。建立了一个带颈动脉分岔血管分支的体循环系统集中参数模型,基于一组可较好地模拟正常生理曲线的参数,通过改变颈内动脉段的集总参数来模拟颈内动脉狭窄,研究了其对颈动脉系统的影响。结果表明:颈内动脉发生狭窄时,会使其自身的流量、压力和颈总动脉的流量发生显著变化。这些变化主要是由液阻和液容的改变引起的,其中液阻的影响更显著。此外,颈内动脉发生狭窄对于颈外动脉的影响较小,对颈总动脉入口压力则不产生影响。由此说明:利用三维计算模型对颈动脉分岔血管进行血流动力学数值模拟时,入口边界条件用入口压力比用入口流量更合适。     

Changes in cardiac output and peripheral flows on pentobarbital anesthesia in the rat

In rats chronically implanted with an electromagnetic flow probe around the ascending aorta, terminal aorta, or superior mesenteric artery as well as arterial and venous indwelling catheters, changes in cardiac output, hindquarter flow, splanchnic flow, and arterial pressure on pentobarbital anesthesia were observed. On intravenous injection of pentobarbital sodium at 30 mg/kg, arterial pressure dropped acutely from an average value of about 105 mmHg to a minimum of about 75 mmHg in about 5 min and then gradually recovered to an average level of about 90 mmHg in 30 min. Cardiac index gradually decreased about 30% on the average in 30 min. Hindquarter flow decreased about 25%. Superior mesenteric flow first increased about 40% within 5 min and then returned almost to the premedication level in 30 min. In adrenalectomized rats there was no decrease of hindquarter flow on pentobarbital anesthesia. The increase in superior mesenteric flow immediately after pentobarbital injection remained almost unchanged after adrenalectomy or splanchnicectomy. It is concluded that an appreciable portion of the decrease in cardiac output on pentobarbital anesthesia is induced by inhibition of tonic adrenomedullary secretion which has a dilating effect on muscle blood vessels through stimulation of beta-receptors. The marked increase in splanchnic flow immediately after pentobarbital injection, which is responsible for the concomitant drop in arterial pressure, is considered to be induced by a direct inhibitory effect of the anesthetic on splanchnic blood vessels.     

A Simulation of Vessel–Clamp Interaction: Transient Closure Dynamics

Cross-clamping of aorta is routinely performed in cardiac surgery. The objective of this study was to simulate cross-clamping of the aorta to elucidate the perturbation of stresses in the wall (solid mechanics) and lumen of the vessel (fluid mechanics). Models of the aorta and clamp were created in Computer Assisted Design and Finite Element Analysis packages. The vessel wall was considered as a non-linear anisotropic material while the fluid was simulated as Newtonian with pulsatile flow. The clamp was applied to produce total occlusion in approximately 1 s. A cylindrical and rectangular geometry for the clamp were considered. High jet speed and flow reversal were demonstrated during clamping. It was found that the clamp design and vessel wall anisotropy affected both the fluid wall shear stress (WSS) and solid stresses in vessel wall. The maximum wall stresses increased by about 170 and 220% during closure in the cases of plate and cylindrical clamps, respectively. The plate clamp design was superior for reduction of both solid stresses as well as fluid shear stresses. The cylindrical clamp causes much larger stresses than the plate clamp in each of the stress components; e.g., radial compression of −180 vs. −50 kPa. Vibrations, flow and WSS oscillations were detected immediately before total vessel occlusion. The present findings provide valuable insights into the mode of tissue injury during clamping and may also be useful for improving surgical clamp designs.     

Sympathetic Control of Cerebral Blood Flow in Acute Arterial Hypertension

The cervical sympathetic chain on one side was stimulated electrically at 10–20 Hz and an acute rise in arterial blood pressure was produced by: intravenous injection of angiotensin, ligation of the thoracic aorta, or ligation of the aorta combined with injection of metaraminol. The blood flow through the cerebrum and the cerebellum was determined by using labelled microspheres. At high blood pressures there was multifocal breakdown of the blood-brain barrier in the cerebrum as indicated by leakage of Evans blue. The breakdown was restricted to the control side or much more marked on that side than on the stimulated side. Sympathetic stimulation prevented also breakdown of the blood-aqueous barrier. The blood flow through the cerebrum on the control side was higher than that on the stimulated side in all experiments. Regions with breakdown of the blood-brain barrier had flow rates which were about 10 times normal values. Cerebellar blood flow was less affected by the hypertension and did not react significantly to sympathetic stimulation. The results indicate that stimulation of the sympathetic nerves to the brain tends to prevent forced dilatation of the arterioles with a resulting regional overperfusion with blood and breakdown of the blood-brain barrier. It is concluded that one role of the sympathetic nerves supplying the brain is to extend the pressure region with autoregulation in its upper part under conditions of a general increase in sympathetic vasomotor activity.