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In vitro reconstruction of hybrid vascular tissue. Hierarchic and oriented cell layers.

Hybrid vascular tissue was hierarchically reconstructed in vitro. A hybrid medial layer composed of type I collagen gel, in which SMCs derived from a mongrel dog were embedded, was formed on the inner surface of a compliant porous polyurethane graft (internal diameter = 3 mm). Endothelial cells (ECs) from the same animal were seeded and cultured on the hybrid media to build an intimal layer. Subsequently, hierarchically structured grafts constructed in this manner were subjected to pulsatile flow (flow rate: 8.5 ml/min; frequency: 60 rpm; amplitude: 5% of graft outer diameter) of culture medium (Medium 199 supplemented with 20% fetal calf serum). After stress loading for as long as 10 days, tissues were morphologically investigated with a light microscope and a scanning electron microscope. Inner surfaces of the hybrid tissues were covered with EC monolayers that aligned along the direction of the flow (i.e., longitudinally). However, SMCs beneath the intima aligned in the circumferential direction. These cellular orientations resembled those in native muscular arteries. The pulsatile stress loaded hybrid tissue mimicked native muscular arteries with respect to hierarchic structure and cellular orientation. In vitro mechanical stress loading on a hybrid graft might provide a high degree of integrity in terms of tissue structure that promises high tolerance toward hydrodynamic stress and regulation of vasomotor tone upon implantation.

Animals↗

Fetal venous and arterial flow velocity wave forms between eight and twenty weeks of gestation.

Our purpose was to study the nature and gestational age dependency of fetal venous Doppler flow velocity wave forms and their relationship with fetal arterial wave forms in early pregnancy. Venous and arterial Doppler recordings were performed in 262 normal singleton pregnancies according to a cross-sectional study design at 8-20 wk of gestation. A statistically significant age-dependent increase is established for the umbilical vein, ductus venosus, and inferior vena cava time-averaged velocity. Umbilical venous pulsatile flow patterns are observed up to 15 wk of gestation. The pulsatility index for veins in all three venous vessels displays a gestational age-dependent reduction. No relation can be established between the pulsatility index for veins and the pulsatility index in the descending aorta and umbilical artery. This may be explained by the fact that the pulsatility index for veins reflects cardiac ventricular preload, whereas the pulsatility index in the arterial vessels reflects downstream impedance at fetal placental level.

Adolescent↗

Arterial 6-keto-PGF1 alpha and TxB2 release in ex vivo perfused canine vessels: effects of pulserate, pulsatility, altered pressure and flow rate.

Certain experimental conditions are known to influence the release of prostacyclin and thromboxane from the vessel wall. The specific effects of altered pulsatility, pressure, and flow rate on intraluminal release of 6-keto-PGF1 alpha and thromboxane B2 were assessed in canine arteries perfused ex vivo for five 15 min periods with arachidonic acid (AA) added during the last period. Control arteries were perfused at 100 mmHg with pulsatile flow of 90 ml/min. Experimental arteries were perfused at 7, 50 and 200 mmHg with pulsatile flow of 90 ml/min, and at 100 mmHg pressure with pulsatile flow of 20, 60, 130 and 180 ml/min, as well as at 100 mmHg with 90 ml/min nonpulsatile flow. Perfusion pump rates of 44 and 96 beats/min were also assessed. The lowest perfusion pressure, 7 mmHg, resulted in a lesser initial release of prostacyclin compared to higher pressures, and there was a tendency to a higher release of prostacyclin with increasing pressures. There was also a tendency for a lesser response to AA in arteries perfused at 200 mmHg, perhaps due to endothelial cell damage. Nonpulsatile flow was associated with a decreased initial release of prostacyclin, and diminished release following addition of AA when compared to pulsatile flow. Altered flow rate elicited no difference in prostacyclin release, although there was a tendency towards a lesser release when perfused at 20 ml/min compared to 130 ml/min or 180 ml/min. Thromboxane release was decreased by nonpulsatile flow but was otherwise unaffected by the experimental conditions tested. It is concluded that pulsatility enhances release of prostacyclin from arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Embolization: critical thrombus height, shear rates, and pulsatility. Patency of blood vessels.

The present article builds on elementary fluid dynamics and previous analyses by the author to delineate approximate boundaries of mural thrombus height Hp, maximum shear rate gamma Max, and flow pulsatility beyond which thrombi are subject to either very high or very low probabilities of embolization. A thrombus height of approximately 0.1 mm emerges as a critical dividing line: Below it, the maximum embolizing shear stress tau s is independent of thrombus height and varies only linearly with shear rate. Above it, tau s quickly approaches a strong quadratic dependence on both thrombus height and shear rate: tau s approximately (Hp gamma)2, significantly increasing the likelihood of an embolizing event. By contrast, convective-diffusive removal of blood components during the initial stages of thrombus formation varies only weakly with gamma 1/3 in all but the smallest vessels. These maximum embolizing stresses are due principally to fluid drag. Acceleration (pulsatile) forces only begin to make their presence felt at gamma less than 500 s-1 and reach parity with fluid drag at gamma approximately 10 s-1, i.e., at a level where the presence of pulsatility is questionable. The results are used to provide maps of domains with high and low probabilities of an embolytic event and of vessel patency. The maps reveal that relatively modest changes in shear rate and/or vessel lumen can cause shifts from high to low likelihood of vessel patency, opening up possible ways of controlling blockage by manipulation of these variables.

Heart Diseases↗

Effect of variations in pressure and flow on the geometry of isolated canine carotid arteries.

A study is described in which the effects of hemodynamics on arterial geometry are investigated in vitro. A novel perfusion apparatus is employed to deliver pulsatile flow through excised canine carotid arteries under carefully controlled conditions. Data of perfused vessel diameter and arterial wall thickness are derived from the radial displacement of the pulsating vessel as measured using a scanning laser micrometer whose accuracy is determined to be 0.0125 mm (0.0005 in). The results of 30 perfusion experiments suggest that the hemodynamic variables of transmural pressure, pulse pressure and flow rate influence vessel size and radial strain. The physiologic implications of these findings are discussed.

Animals↗

The effect of once-daily latanoprost on intraocular pressure and pulsatile ocular blood flow in normal tension glaucoma.

PURPOSE: To determine the effect of once-daily 0.005% latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in patients with normal tension glaucoma (NTG). METHODS: The diurnal IOP and sitting POBF were determined for 32 eyes of 19 NTG patients after a washout period. The subjects were treated with 0.005% latanoprost for 3-4 weeks and the measurements repeated. Statistical analysis was performed using the Wilcoxon signed rank test. RESULTS: Median IOP before and after treatment were 19 and 15 mmHg respectively (p < 0.001). The IOP reduction correlated with the initial IOP before treatment (p < 0.01) and was accompanied by an increase in median POBF from 656 to 796 microliters/min (p < 0.001). CONCLUSIONS: Once-daily treatment with 0.005% latanoprost provides a significant and stable IOP reduction in the majority of NTG patients after short-term treatment. This is accompanied by a significant increase in POBF.

Administration, Topical↗

Pulsatile ocular blood flow change after treatment with systemic steroid in patients with Graves' ophthalmopathy.

PURPOSE: Our previous study has demonstrated an impairment of pulsatile ocular blood flow (POBF) in patients with Graves'ophthalmopathy (GO). Here we further evaluate the haemodynamic change in GO patients after systemic steroid. METHODS: In a prospective, interventional, consecutive clinical case series, all patients with active and moderately severe GO who underwent systemic steroid treatment were evaluated. The change of POBF and the clinical activity and severity of the disease were assessed. RESULTS: In total, 11 patients underwent intravenous methylprednisolone pulse therapy followed by 2-month oral prednisolone therapy. POBF improved from a mean value of 476.5 to 614.7 microl/min (P<0.001) after treatment. Likewise, the mean clinical activity score reduced from 4.8 to 1.6. However, systemic steroid had less effect on the severity of GO. It also revealed that there is a greater improvement of POBF in those with more clinical activity score (>4) at the onset. CONCLUSIONS: Following treatment with systemic steroid we have demonstrated a significant improvement in POBF in patients with GO.

Administration, Oral↗

The relationship of pulsatile cerebrospinal fluid flow to cerebral blood flow and intracranial pressure: a new theoretical model.

An electrical-equivalent circuit model of the cerebrovascular system is proposed, components of which directly relate to cerebrospinal fluid (CSF) compartment compliance and the determination of intracranial pressure (ICP). The model is based on three premises: 1) Under normal, physiologic conditions, the conversion of pulsatile arterial to nonpulsatile venous flow occurs primarily as a result of arterial compliance. Nonpulsatile venous flow is advantageous because less energy is required to maintain constant flow through the venous system, which comprises 75-80% of total blood volume. 2) Dynamic CSF movement across the foramen magnum is the primary facilitator by which intracranial arterial expansion occurs. Interference of the displacement of CSF during systole results in pulsatile venous flow and increased venous flow impedance. 3) Tissue hydrostatic pressure (here defined as ICP) is a dependent variable which is a function of capillary hydrostatic pressure and the osmotic/oncotic pressure gradient created by the blood-brain-barrier (BBB). An interference of transcranial CSF movement results in a decrease in cerebral blood flow (CBF) due to inertial effects impeding pulsatile venous flow. Feedback regulation in response to this decreased CBF leads to arteriolar vasodilatation (decreased resistance), thereby lowering the pressure difference between internal carotid and capillary pressures. Assuming no changes in the BBB potential, ICP increases linearly as capillary pressure increases.

Blood Flow Velocity↗

MR-velocity mapping in vascular stents to assess peak systolic velocity. In vitro comparison of various stent designs made of Stainless Steel and Nitinol.

INTRODUCTION: Peak systolic velocity (PSV) measurements of blood flow inside vascular stents allow reliable detection of in-stent re-stenosis. The purpose of this in vitro study was to evaluate the feasibility of obtaining PSV measurements inside vascular stents made of Stainless Steel and Nitinol, using a velocity encoded MR technique. MATERIALS/METHODS: In a flow phantom, stents of Stainless Steel and Nitinol were studied. The phantom was integrated into a closed-tubing circuit driven by a MR dedicated pulsatile flow pump. MR imaging was performed on a 1.5 T system. The PSV in the tube without stent was used as the gold standard to determine the accuracy and the variability (paired t-test and Pittman's test) of the PSV measurements inside the stents. RESULTS: PSV values inside the stents showed percentual difference in mean of -15 to 21% (P < 0.05) at a pump setting of 10 and 20 ml/s. CONCLUSION: PSV measurements can be accurately obtained inside stents made of Stainless Steel and Nitinol. MR-velocity measurements may be used in patients to non-invasively evaluate stent patency and in-stent re-stenosis.

Alloys↗

A study of the wall shear rate distribution near the end-to-end anastomosis of a rigid graft and a compliant artery.

The development of intimal hyperplasia in the anastomotic region of a vascular graft which does not match the compliance of the parent artery may be related to altered wall shear rates near the anastomosis. The purpose of this study is to determine the effect of radial wall motion and the phase angle between pressure and flow waves (impedance phase angle) on the wall shear rate distribution near an end-to-end vascular graft anastomosis model incorporating a rigid graft and a compliant artery. The wall shear rate is determined from near-wall velocity profiles obtained by a flow visualization method using a photo-chromic dye for different locations near the anastomosis. The results show that the mean wall shear rate under pulsatile flow conditions is 15-30% lower than under steady flow conditions at the same mean flow rate. The effect of the impedance phase angle on the mean wall shear rate is shown to be small, but its effect on the amplitude of the wall shear rate is not negligible. For our anastomosis model which has well-matched diameters at the mean pressure, the mean shear rates at the distal sites are lower than at the proximal sites by 15-23%. We suppose that the differences in the mean wall shear rate between the proximal and distal sites are related to the convergent/divergent geometry caused by the mismatch of the compliance. Since the distal side of the anastomosis is more prone to intimal hyperplasia, lower shear rates near the distal anastomosis favor the hypothesis that low/oscillatory wall shear rates lead to intimal hyperplasia.

Anastomosis, Surgical↗

Finite element methods of studying mechanical factors in blood flow.

This paper reviews some biomechanical analyses of blood flow in large arteries based on a general computer modeling using the finite element method. We study the following question: What is the role played by the interrelated factors of mechanical stress, flow irregularities, and diffusion through the endothelium on the etiology of atherosclerosis or the aggravation of vascular injury. It presents the computational features of the method and stresses the physiological significance of the results, such as the effect of geometric complexities, material nonlinearities, and non-Newtonian rheology of the blood. The specific mechanical and fluid dynamic factors analyzed are wall shear stress, flow profiles, and pressure variations. After simulating tubes of circular cross section, we apply the analysis to a number of physiological situations of significance, including blood flow in the entrance region, at bifurcations, in the annular region between an inserted catheter of varying diameter and the vessel. A model study of pulsatile flow in a 60 degree bifurcated channel of velocity profiles provided corroborative measurements of these processes with special emphasis on reversed or distributed flow conditions. The corresponding analysis was extended to the situation in which flow separates and reverses in the neighborhood of stagnation points. This required developing the nonlinear expression for the convective velocity change in the medium. A computer algorithm was developed to handle simultaneous effects of pressure and viscous forces on velocity change across the element and applied to the canine prebranch arterial segment. For mean physiological flow conditions, low shear stresses (0-10 dynes/cm2) are predicted near the wall in the diverging plane, higher values (50 dynes/cm2) along the converging sides of the wall. Backflow is predicted along the outer wall, pressure recovery prior to and into the branches, and a peak shear at the divider lip.

Arteriosclerosis↗

Observations on flow characteristics of passive external aortic shunts.

Extraluminal heparin-bonded shunts have been recommended to support the distal circulation and decompress the proximal vascular bed during procedures that require interruption of flow through the thoracic aorta. Shunts that originate in either the left ventricle or the proximal aorta are generally viewed as hemodynamically similar, despite incomplete documentation of their flow characteristics. The present study was conducted to further define these hemodynamic properties. Identical extraluminal shunts were placed from the left ventricular apex and aortic arch to the distal thoracic aorta in mongrel dogs. Simultaneous pressure and Doppler flow velocities were recorded in the carotid and femoral arteries. Computer-enhanced composite waveforms were used to assist data analysis. When compared to ventricular cannulation, aortic cannulation provided improved proximal decompression and increased mean distal flow. In addition, significant diastolic flow reversal was recorded in the distal circulation when ventricular cannulation was employed. On the other hand, ventricular cannulation was associated with the preservation of pulsatile flow, whereas flow generated by aortic cannulation was linear. It is concluded that extraluminal shunts that originate in the left ventricle and the proximal aorta have distinct hemodynamic properties. These differences may be clinically important in specific situations.

Animals↗

Studies of skeletal tracer kinetics. III. Tc-99m(Sn)methylenediphosphonate uptake in the canine tibia as a function of blood flow.

Experiments were performed in 14 dogs to study the effect of changes in bone blood flow on the tibial uptake of the skeletal tracer Tc-99m(Sn)methylenediphosphonate (Tc-99m MDP). Aortic blood was diverted through a pulsatile-flow pump in order to monitor and control femoral arterial blood flow. Tibial nutrient perfusion, as measured with labeled microspheres, paralleled the changes in arterial flow. We found that increments in bone blood flow up to four times normal produced only minimal augmentation of Tc-99m MDP uptake (mean = 33%), a markedly nonproportional relationship. The data points clustered about a predicted curve produced by perturbing the rate constants of a seven-compartment model obtained in normal dogs. These findings indicate that bone uptake of Tc-99m MDP is diffusion-limited, and they therefore cast doubt upon the validity of a method used for many years for estimating bone blood flow, the so-called skeletal tracer clearance technique. Nerve section, performed in 14 other dogs, augmented Tc-99m MDP uptake by about 50% at supranormal flows, suggesting a parallel-flow model of the microcirculation in bone, under sympathetic control. Such a model satisfactorily explains many scintigraphic findings in disease states.

Animals↗

[Flow time analysis in sonographic flow measurements: an in vitro measurement for testing their accuracy].

Flow-time analysis is a new technique for colour coded sonographic flow measurements. The measurements depend on a pattern of ultrasound pulses and have some significant advantages compared with Doppler procedures. The accuracy of the method and possible sources of error have been studied under experimental conditions. Measurements on continuous blood flow showed a correlation of r > 0.99 for duplex sonography and of r > 0.93 for flow-time analysis. For this method, the colour coding parameters must be optimal in order to achieve high accuracy. Under these conditions quantitative measurement of pulsatile flow also becomes possible during colour mode.

Color↗

[Diagnostic significance of specific features of blood flow in the vicinity of stenosis. Model experiments].

Axisymmetric stenoses made of teflon were inserted into PCV tubes, 0.39-0.4 cm in diameter. There was a 28-93% reduction in the area of vessel lumen. The pulsatile flow of water-glycerol mixture containing talcum particles was maintained by an artificial circulatory device. The Doppler ultrasound system was used to measure flow characteristics. The background (remote from the stenosis) values were studied by dispersion analysis. The dependence of the values in the area of stenosis upon the degrees of stenosis was described by the parabolic function. The combination of the function with an upper 95% background limit shows that the method records luminal changes nearly by 20%.

Blood Circulation↗

A prospective evaluation of the pulsatile assist device.

Conversion of roller pump flow to pulsatile flow by the pulsatile assist device (PAD) is said to result in improved myocardial preservation and a decrease in the incidence of perioperative myocardial infarction. The clinical advantages of the PAD were evaluated in a prospective randomized study of 100 consecutive coronary artery bypass operations. Serial electrocardiograms, creatine phosphokinase isoenzyme studies, and myocardial scans with technetium-labeled pyrophosphate failed to demonstrate any signficiant difference between patients with the PAD and those receiving nonpulsatile flow. Plasma hemoglobin levels were significantly higher in the PAD group indicating increased blood trauma. Other potential disadvantages of the PAD are discussed. Based on this study, we see few advantages of the PAD in routine coronary bypass operations.

Coronary Artery Bypass↗

MR measurement of time-dependent blood pressure variations.

An MR imaging method for measuring intravascular pressure variations is introduced. The technique is based on estimates of vascular compliance and vessel distension, which are obtained from a correlation of spatial and temporal velocity derivatives and measurements of the velocity gradient in the direction of flow, respectively. The accuracy of the technique was determined in vitro through a comparison of MR and transducer pressure measurements obtained in distensible vessel phantoms undergoing pulsatile flow. Results indicated that a root-mean-square error of 4-12% can be expected in phantoms covering a physiological range of compliance. In vivo feasibility was demonstrated by thoracic aorta pressure measurements, which produced pressure waveforms with an expected shape and magnitude.

Adult↗

Lumped model of terminal aortic impedance in the dog.

The aim of this study was the formulation of a minimal lumped model of the aortic impedance as seen in the abdominal aorta just downstream of the origin of renal arteries. At this location simultaneous measurements of pressure and flow were taken in four anesthetized and open-chest dogs (weight, 30.9 +/- 5.8 kg) under basal, vasodilated (sodium nitroprusside) and vasoconstricted (methoxamine) conditions. Using these measurements we identified and compared three lumped models, A, B, and C, with decreasing complexity from A to C. The frequency response of these models was given the general form of peripheral resistance, Rp, multiplied by the ratio between (a) two zeros and two poles (model A); (b) two zeros and one pole (model B); and (c) one zero and one pole (model C). Rp was calculated as the ratio of mean pressure to mean flow. The other model parameters (time constants, damping factors, and natural frequencies) were estimated by minimizing the sum of squared differences between experimental and model generated pulsatile flows. After parameter estimation, the F-test was applied to compare the goodness of data fit obtained from the three models. Results of this test and the analysis of parameter estimation errors indicated that model B was preferable with respect to models A and C. The analysis of general model performance was followed by a consideration of alternative specific model structures that are physically realizable. With the aid of a determined model structure we evaluated the overall compliance of terminal aortic circulation under a variety of vascular states induced by injection of vasoactive agents.

Animals↗