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PubMed1985

Experimental investigation of branch flow ratio, angle, and Reynolds number effects on the pressure and flow fields in arterial branch models.

An experimental investigation was carried out to acquire an understanding of local pressure changes and flow along the main lumen of arterial branch models similar to the femoral artery of man with three different branch angles (30, 60, and 90 deg) and side branch to the main lumen diameter ratio of 0.4. Effects of branch to main lumen flow rate ratios and physiological Reynolds numbers were found to be significant on the local pressure changes, while that of branch angle was also found to be important. The flow visualization study revealed that the flow separated in the main lumen near the branch junction when the pressure rise coefficient along the main lumen was above a critical value (i.e., 0.35 - 0.46), which was observed to be a function of the Reynolds number. The critical value of the branch to main lumen flow rate ratio was found to be about 0.38 - 0.44 also depending on the Reynolds number. Time averaged pressure distributions for pulsatile flow were similar in trend to steady flow values although they differed somewhat in detail in the main lumen in the branch region.

Blood Flow Velocity↗
PubMed2000

The power-velocity integral at the vena contracta: A new method for direct quantification of regurgitant volume flow.

BACKGROUND: Noninvasive quantification of regurgitation is limited because Doppler measures velocity, not flow. Because backscattered Doppler power is proportional to sonified blood volume, power times velocity should be proportional to flow rate. Early studies, however, suggested that this held only for laminar flow, not for regurgitant jets, in which turbulence and fluid entrainment augment scatter. We therefore hypothesized that this Doppler power principle can be applied at the proximal vena contracta, where flow is laminar before entrainment, so that the power-times-velocity integral should vary linearly with flow rate and its time integral with stroke volume (SV). METHODS AND RESULTS: This was tested in vitro with steady and pulsatile flow through 0.07- to 0.8-cm(2) orifices and in 36 hemodynamic stages in vivo, replacing the left atrium with a rigid chamber and column for direct visual recording of mitral regurgitant SV (MRSV). In 12 patients, MRSV was compared with MRI mitral inflow minus aortic outflow and in 11 patients with 3D echo left ventricular ejection volume-Doppler aortic forward SV. Vena contracta power in the narrow high-velocity spectrum from a broad measuring beam was calibrated against that from a narrow reference beam of known area. Calculated and actual flow rates and SV correlated well in vitro (r=0.99, 0.99; error=-1.6+/-2.5 mL/s, -2. 4+/-2.9 mL), in vivo (MRSV: r=0.98, error=0.04+/-0.87 mL), and in patients (MRSV: r=0.98, error=-2.8+/-4.5 mL). CONCLUSIONS: The power-velocity integral at the vena contracta provides an accurate direct measurement of regurgitant flow, overcoming the limitations of existing Doppler techniques.

Animals↗
PubMed1986

Flow in tubes and arteries--a comparison.

The cardiovascular circulatory system of the human body can be compared with a network of tubes. It consists of a pump and a system of branched vessels. The arteries transport the blood to the periphery in a manner similar to that of a water supply network. It is important to know what kind of forces act upon "fittings", bends and bifurcations. It is also essential to assess whether the flow is laminar or turbulent, attached or separated. The flow should be optimized in such a manner as to minimize the drop in pressure. This means that no additional pressure loss due to separation or turbulence should occur, since such losses increase the pump power requirements. The loss appears in heating and acoustic energy. The necessary understanding of blood flow in human vessels is also of great interest to physicians since it is believed that the local flow behavior of blood determines the formation of atherosclerotic plaques. As in tubing systems, deposits in blood vessels are found close to bends and bifurcations. These deposits lead to impaired cerebral circulation and to myocardial infarction. A partial review of recent research into the details of flow behavior (like separation, stagnation and reattachment points) in bends and bifurcations of arterial models is presented. Studies involving steady and pulsatile flow conditions in rigid and elastic models with Newtonian and non-Newtonian fluids are shown here. The most important differences between blood vessels and tubes are discussed. This modern biofluidmechanical approach of detailed flow examination is compared with the more classical hemodynamic approach considering only gross features such as pressure loss coefficients.

Arteries↗
PubMed1987

Haemodynamic and rheological aspects of vascular grafts.

1) We now know that although the basic relationship of pressure, flow and resistance as expressed by the Poiseuille equation is useful in understanding basic regional haemodynamics, it cannot be applied to pulsatile flow and particularly if any measurements are to be made in the study of graft haemodynamics. Measurements of pressure wave velocity, and flow wave velocity with calculations of wall compliance and impedance are more appropriate. 2) The clinical performance of a graft depends on the mechanical properties of the graft and the response of the body to the prosthesis in terms of fibrous tissue reaction and thrombus deposition. 3) We should aim for grafts with low thrombogenicity, and a compliance which after implantation matches that of the arterial wall of the patient. 4) Although the animal experiments of the 1980s have given us enough indications of what we should aim for, and no doubt they will continue to be the ground for preclinical assessment, the time has come for us to develop techniques that will allow us to do the same measurements in our patients noninvasively. The high resolution M-mode and B-mode echographic vascular imaging and Doppler ultrasonic techniques with real-time fast Fourier analysis are with us and should form the spearhead for such an approach. By measuring graft compliance, thrombus deposition and flow velocities in the grafts implanted in our patients we shall bridge the gap between animal experiments and clinical evaluation, providing the manufacturers with enough information that points the direction towards more efficient grafts.

Blood Vessel Prosthesis↗
PubMed1985

Haemodynamic aspects of vascular grafting.

We now know that although the basic relationship of pressure, flow and resistance as expressed by the Poiseuille equation is useful in understanding basic regional haemodynamics, it cannot be applied to pulsatile flow and particularly if any measurements are to be made in the study of graft haemodynamics. Measurements of pressure wave velocity, and flow wave velocity with calculation of wall compliance and impedance are more appropriate. The clinical performance of a graft depends on the mechanical properties of the graft and the response of the body to the prosthesis in terms of fibrous tissue reaction and thrombus deposition. We should aim for grafts with low thrombogenicity, and a compliance which after implantation matches that of the arterial wall of the patient. Although the animal experiments of the 1980s have given us enough indications of what we should aim for, and no doubt they will continue to be the ground for preclinical assessment, the time has come for us to develop techniques that will allow us to do the same measurements in our patients noninvasively. The high resolution M-mode and B-mode echographic vascular imaging and Doppler ultrasonic techniques with real-time fast Fourier analysis are with us and should form the spearhead for such an approach. By measuring graft compliance, thrombus deposition and flow velocities in the grafts implanted in our patients we shall bridge the gap between animal experiments and clinical evaluation, providing the manufactures with enough information that points the direction towards more efficient grafts.

Animals↗
PubMedDate not supplied

Morphology and integrity of endothelial cell monolayers inside a ventricle shaped perfusion chamber.

The long-term maintenance of patients with failing hearts on cardiac prostheses requires prevention of device related thromboembolic events. This challenge is being addressed by endothelialization of the blood sacs. However, the practice of establishing and maintaining a durable endothelial cell monolayer inside a beating prosthesis has not been fully realized. Thus, before exposing endothelial cell monolayers to the hemodynamics inside an artificial heart, the authors studied the effect of various flow patterns in a ventricle shaped chamber on the integrity and morphology of the endothelium. After 20 hours of superfusion by pulsatile flow, there were no denudation signs in the jet, where shear stress was 1.5 dynes/cm2. However, there was measurable damage to the monolayer close to the periphery of the eddies (turbulent flow) at 0.15 dynes/cm2. In either case, there were no signs of cell alignment with the flow, but there were changes in cell morphology compared with that of static control. These findings suggest that adjustment of endothelial cells in response to frictional forces occurs even at low shear stresses and that random velocity fluctuations might jeopardize the integrity of endothelial cell monolayers.

Animals↗
PubMed2003

The effect of simulated obstructive apnoea on intraocular pressure and pulsatile ocular blood flow in healthy young adults.

AIM: To investigate the effect of negative inspiratory effort, as generated by the Mueller manoeuvre, on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in healthy young adults. METHODS: Seven volunteers with no history of systemic or ocular disease were recruited (mean age 30.7 years, range 25-40 years, M/F: 4/3). After initial instruction and practice of the Mueller manoeuvre, baseline measurements of IOP and POBF were obtained for both eyes after 10 and 15 minutes of rest, respectively, in the supine position. Thereafter, the Mueller manoeuvre was performed creating a mouthpiece pressure of -20 cm H(2)O, for at least 15 seconds followed by a 5 minute rest. The manoeuvre was repeated with a mouthpiece pressure of -40 cm H(2)O. IOP and POBF were measured 5-15 seconds into the manoeuvre for both -20 cm H(2)O (M2A) and -40 cm H(2)O (M4A) and directly upon recovery (after two respiratory cycles) from each manoeuvre (M2B, M4B). Baseline measurements were compared using paired t test, whereas manoeuvre induced changes in IOP and POBF were analysed individually using repeated measures ANOVA with Student-Newman Keuls post hoc analyses. Linear regression analysis was used to investigate a dose-response effect. RESULTS: No significant differences were found between baseline measurements so they were subsequently pooled. There was a significant decrease in IOP for M2B (-9.2%, p<0.05), M4A (-13.8%, p<0.05), and M4B (-15.6%, p<0.05), relative to baseline. A dose-response relation was found for the effect of mouthpiece pressure on measurements 5-10 seconds into the manoeuvre (M2A and M4A, r = 0.54, p = 0.045). There was a trend of increased POBF relative to baseline for all measurements; however, significance was reached for M4B only (p = 0.039). CONCLUSION: It was shown that forced inspiratory efforts as generated by the Mueller manoeuvre are associated with a dose dependent decrease in IOP and a concomitant increase in pulsatile ocular blood flow.

Adult↗
PubMed2006

Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific.

Flow patterns in blood vessels contribute to focal distribution of atherosclerosis; the underlying mechanotransduction pathways remain to be investigated. We demonstrate that different flow patterns elicit distinct responses of Krüppel-like factor-2 (KLF2) in endothelial cells (ECs) in vitro and in vivo. While pulsatile flow with a significant forward direction induced sustained expression of KLF2 in cultured ECs, oscillatory flow with little forward direction caused prolonged suppression after a transient induction. The suppressive effect of oscillatory flow was Src-dependent. Immunohistochemical studies on ECs at arterial branch points revealed that KLF2 protein levels were related to local hemodynamics. Such flow-associated expression patterns were also demonstrated in a rat aortic restenosis model. Inhibition of KLF2 with siRNA sensitized ECs to oxidized LDL-induced apoptosis, indicating a protective role of KLF2. In conclusion, differential regulation of KLF2 may mediate the distinct vascular effects induced by various patterns of shear stress.

Animals↗
PubMed1996

Validation of volume flow measurements in blood vessels with quantitative color velocity imaging using a physiologic model of the circulation.

RATIONALE AND OBJECTIVES: Color velocity imaging-quantitative (CVI-Q) is a new sonographic technique designed to measure volume flow (VF) in blood vessels. We attempted to validate VF measurements with CVI-Q in an in vitro model of the circulation. METHODS: We validated CVI-Q in a flow phantom mimicking physiologic conditions by connecting isolated porcine arteries 4-14 mm in diameter to a calibrated perfusion roller pump generating pulsatile flow with porcine blood. Pump flow was varied stepwise from 0 to 1,000 ml/min. CVI-Q VF measurements were performed using a 7.5-MHz linear array transducer. VF results then were compared with pump flow calibration values through linear regression. RESULTS: A good correlation (r2 = .98-.99, slope = 0.88-1.02) was obtained from 0 to 400-600 ml/min. The degree of correlation depended on vessel diameter, with linearity being maintained over a somewhat larger range in medium-sized vessels. At higher flows, variability increased significantly. CONCLUSION: VF measurements with CVI-Q are accurate in a physiologic flow range. At supraphysiologic flow rates, as are encountered within arteriovenous fistulae, CVI-Q may give inaccurate results. Awareness of possible pitfalls and limitations of the technique is important for obtaining accurate and reproducible results.

Animals↗
PubMedDate not supplied

Hemodynamic and gas transfer properties of a compliant thoracic artificial lung.

A compliant thoracic artificial lung (TAL) has been developed for acute respiratory failure or as a bridge to transplantation. The development goal was to increase TAL compliance, lower TAL impedance, and improve right ventricular function during use. Prototypes were tested in vitro and in vivo in eight pigs between 67 and 79 kg to determine hemodynamic and gas transfer properties. The in vitro compliance was 16.2 +/- 4.4 ml/mm Hg at pressures < 7.8 mm Hg and 4.3 +/- 1.1 ml/mm Hg above 7.8 mm Hg. In vivo, this compliance significantly reduced blood flow pulsatility from 1.7 at the inlet to 0.36 at the outlet. Device resistance was 1.9 and 1.8 mm Hg/(L/min) at a flow rate of 4 L/min in vitro and in vivo, respectively. Approximately 75% of the resistance was at the inlet and outlet. In vivo TAL O2 and CO2 transfer rates were 188 and 186 ml/min, respectively, at 4 L/min of blood and gas flow, and average outlet O2 saturations exceeded 98% for average flow rates up to and including the maximum tested, 5.3 L/min. The new design has a markedly improved compliance and excellent gas transfer but also possesses inlet and outlet resistances that must be reduced in future designs.

Animals↗
PubMed1995

Correlation between LDA and ultrasound heart catheter measurements in a stenosed arterial model.

Ultrasound heart catheters are used to measure the velocity in coronary arteries. However, the act of introducing a catheter into the vessel disturbs the very flow being measured. We used laser Doppler anemometry to measure the velocity distribution in an axially symmetric model, both with and without a catheter inserted. The catheter reduced the center-line velocity by as much as 60 percent at a distance of 2 mm downstream from the catheter, and by as much as 25 percent at a distance of 10 mm. This means the velocity measured with an ultrasound catheter does not show the maximum velocity of the undisturbed flow in the tube center. In the constriction, however, the measured velocities with the LDA and ultrasound catheter are almost the same. Thus, catheter measurements in the stenosis achieve accurate results. The velocity profile in the stenosed areas is flattened over nearly the whole cross section. The velocity is extremely reduced only close to the wall. The measurements outside of the stenosis lead to large differences which need to be studied carefully in the future. The disturbed flow finally disappeared 15 mm downstream of the catheter. The measurements were done at steady flow using a glycerine water solution with a dynamic viscosity of 4.35 mPas. In future studies, these experiments will be repeated for pulsatile flow conditions using non-Newtonian blood-like fluids.

Blood Flow Velocity↗
PubMed1984

Pulsed Doppler assessment of deep femoral artery hemodynamics: a preliminary report.

The functional capability of the deep femoral artery (DFA) as a collateral channel is an important feature in patients suffering peripheral arterial occlusive disease (PAOD). A noninvasive method of indirect quantification of the DFA blood flow volume is presented. In normal lower limbs, it was found that the common femoral artery (CFA) mean blood flow volume was maintained at 59% of its resting value when the superficial femoral artery (SFA) was occluded by a pneumatic cuff placed around the thigh. The reduction of the mean flow volume is mainly due to an increase of the diastolic backward flow, while the maximum systolic flow remains constant. In a few patients with various degrees of stenosis of the DFA, we observed a much greater drop in mean CFA blood flow volume than in normal subjects. On the basis of this preliminary study, we conclude that: --When the normal SFA is occluded, pulsatile flow through the CFA is maintained. --Occlusion flow reflects the runoff and the compliance of the DFA bed. --Occlusion flow is diminished in patients with DFA stenosis. It is suggested that this non-invasive test might help the physician to assess the involvement of the DFA in PAOD. Further investigation is needed to establish the correlation between quantitative occlusion blood flow volume and the degree of DFA stenosis.

Adult↗
PubMed1998

[A surgical case of angina pectoris with a severe stenosis of Lt. mid-cerebral artery: the usefulness of the monitoring of cerebral blood flow].

A 64-year-old male patient had two episodes of transient ischemic attack and a cerebral infarction. Cerebral angiography showed 50% stenosis at the junction of left internal carotid artery and 90% stenosis at left mid-cerebral artery (MCA). Coronary angiography showed two vessel disease with arteriosclerotic change and underwent coronary artery bypass grafting. To prevent intraoperative cerebral infarction, we used brain protect solution just before starting ECC, set perfusion flow around 3 l/min/m2, monitored the flow of left MCA using Transcranial Doppler (TCD) and the saturation of left internal jugular vein (SjO2) continuously. PaCO2 was controlled around 45 mmHg. TCD showed good pulsatile flow, and SjO2 was kept over 60%. The patient recovered consciousness 2 hours after operation in the intensive care unit without paresthesia. We thought the number of open-heart cases with cerebrovascular disease increased, and pulsatile low of ECC by intraaortic balloon pumping and the monitoring of SjO2 are useful for the cases.

Angina Pectoris↗
PubMed1989

Influences of nifedipine on vascular conductance of portally drained viscera, liver and kidney.

Nifedipine is a potent vasodilator, which induces various dose-related hemodynamic responses in the gastrointestinal tract, liver and kidney. Blood flow was assessed in anesthetized dogs with non-cannulating electromagnetic flow sensors. Nifedipine was injected into a brachial vein at intervals of 2 min in graded doses from 1-16 micrograms.kg-1. The pulsatile flow and pressure signals were analog-digital converted and processed by a computer program to obtain mean flow (ml.min-1) and mean pressure (mm Hg) values for every 3 s. The vascular data are presented as conductance. The arterial pressure decreased 45% while vascular conductance in vessels of the stomach, duodenum, small and large bowel increased between 75 and 128%. No response was observed in the splenic and common hepatic artery. An increase of resistance in the hepatic artery proper, while portal flow increased suggests that there were changes in liver metabolism. Although the literature indicates a decrease in renal vascular resistance, we encountered a decrease in flow but no change in resistance. Neither did we find an increase in heart rate. We propose that small intravenous doses of nifedipine reduce the afterload of the left ventricle.

Animals↗
PubMed2002

An in vitro system for Doppler ultrasound flow studies in the stenosed carotid artery bifurcation.

To investigate the correlation between disease severity and Doppler spectral measurements in the carotid artery bifurcation, a unique in vitro system has been developed that mimics the human vasculature with respect to both anatomy and flow perfusion. Agar-based carotid phantoms are perfused with a blood-mimicking fluid using a computer-controlled pump and realistic pulsatile flow waveform. A three-axis translational stage allows the lumen to be interrogated with a 0.6-microL Doppler sample volume at the desired spatial intervals using a semiautomated acquisition system, to collect 10 cardiac cycles of gated quadrature data at each site. Off-line analysis, including a 1024-point FFT, produces a 4-D (i.e., time-varying 3-D) Doppler velocity data set with 1.3-cm/s velocity resolution and 12-ms temporal resolution. Using this system, in vitro flow in bifurcations with both normal and stenosed lumen geometry (from 30% to 80% stenosis by NASCET criteria) can be studied, along with the effect of factors, such as stenosis geometry (concentric vs. eccentric) and flow rate, on the observed Doppler ultrasound (US) spectra and haemodynamic patterns.

Blood Flow Velocity↗
PubMed2006

Flow-activated chloride channels in vascular endothelium. Shear stress sensitivity, desensitization dynamics, and physiological implications.

Although activation of outward rectifying Cl(-) channels is one of the fastest responses of endothelial cells (ECs) to shear stress, little is known about these channels. In this study, we used whole-cell patch clamp recordings to characterize the flow-activated Cl(-) current in bovine aortic ECs (BAECs). Application of shear stress induced rapid development of a Cl(-) current that was effectively blocked by the Cl(-) channel antagonist 5-nitro-2-(3-phenopropylamino)benzoic acid (100 microM). The current initiated at a shear stress as low as 0.3 dyne/cm(2), attained its peak within minutes of flow onset, and saturated above 3.5 dynes/cm(2) approximately 2.5-3.5-fold increase over pre-flow levels). The Cl(-) current desensitized slowly in response to sustained flow, and step increases in shear stress elicited increased current only if the shear stress levels were below the 3.5 dynes/cm(2) saturation level. Oscillatory flow with a physiological oscillation frequency of 1 Hz, as occurs in disturbed flow zones prone to atherosclerosis, failed to elicit the Cl(-) current, whereas lower oscillation frequencies led to partial recovery of the current. Nonreversing pulsatile flow, generally considered protective of atherosclerosis, was as effective in eliciting the current as steady flow. Measurements using fluids of different viscosities indicated that the Cl(-) current is responsive to shear stress rather than shear rate. Blocking the flow-activated Cl(-) current abolished flow-induced Akt phosphorylation in BAECs, whereas blocking flow-sensitive K(+) currents had no effect, suggesting that flow-activated Cl(-) channels play an important role in regulating EC flow signaling.

Animals↗
PubMed1999

[The DeBakey VAD axial flow pump: first clinical experience with a new generation of implantable, nonpulsatile blood pumps for long-term support prior to transplantation].

Because of the high frequency of acute hemodynamic deterioration in patients awaiting cardiac transplantation, mechanical techniques of circulatory support to bridge the period until transplantation have become a standard clinical procedure. Continuous-flow rotary blood pumps offer exciting new perspectives in terms of ventricular assistance and/or as a total cardiac substitute. A DeBakey VAD axial flow pump was implanted in two male patients (aged 44 and 65 years, respectively) suffering from end-stage left heart failure. In the initial postoperative period the mean flow rate of the pump was 3.9 +/- 0.5 l/min. In both patients, the early postoperative phase was characterised by a completely non-pulsatile flow profile. Two weeks after implantation and partial recovery of the natural left ventricle, increasing pulse pressures became evident and net flow increased to 4.5 +/- 0.6 l/min. Patients were mobilised and made to under-go regular physical training. Hemolysis produced by the pump was low while free haemoglobin stayed in physiological ranges, increasing only slightly from 2.1 +/- 0.8 mg/dl preoperatively to 3.0 +/- 1.5 mg/dl ten weeks after implantation. One patient was successfully transplanted on day 74 after implantation of the DeBakey VAD while the second patient is, after 110 days of pumping, still waiting for transplantation. This first experience concerning clinical implantation of the DeBakey VAD axial flow pump showed that the device is promising as a means of providing mechanical support to bridge the period until cardiac transplantation.

Adult↗
PubMed2002

Tissue engineering of functional trileaflet heart valves from human marrow stromal cells.

BACKGROUND: We previously demonstrated the successful tissue engineering and implantation of functioning autologous heart valves based on vascular-derived cells. Human marrow stromal cells (MSC) exhibit the potential to differentiate into multiple cell-lineages and can be easily obtained clinically. The feasibility of creating tissue engineered heart valves (TEHV) from MSC as an alternative cell source, and the impact of a biomimetic in vitro environment on tissue differentiation was investigated. METHODS AND RESULTS: Human MSC were isolated, expanded in culture, and characterized by flow-cytometry and immunohistochemistry. Trileaflet heart valves fabricated from rapidly bioabsorbable polymers were seeded with MSC and grown in vitro in a pulsatile-flow-bioreactor. Morphological characterization included histology and electron microscopy (EM). Extracellular matrix (ECM)-formation was analyzed by immunohistochemistry, ECM protein content (collagen, glycosaminoglycan) and cell proliferation (DNA) were biochemically quantified. Biomechanical evaluation was performed using Instron(TM). In all valves synchronous opening and closing was observed in the bioreactor. Flow-cytometry of MSC pre-seeding was positive for ASMA, vimentin, negative for CD 31, LDL, CD 14. Histology of the TEHV-leaflets demonstrated viable tissue and ECM formation. EM demonstrated cell elements typical of viable, secretionally active myofibroblasts (actin/myosin filaments, collagen fibrils, elastin) and confluent, homogenous tissue surfaces. Collagen types I, III, ASMA, and vimentin were detected in the TEHV-leaflets. Mechanical properties of the TEHV-leaflets were comparable to native tissue. CONCLUSION: Generation of functional TEHV from human MSC was feasible utilizing a biomimetic in vitro environment. The neo-tissue showed morphological features and mechanical properties of human native-heart-valve tissue. The human MSC demonstrated characteristics of myofibroblast differentiation.

Absorbable Implants↗