To investigate the potential role of fluid mechanical factors in the localized genesis and development of atherosclerotic lesions in humans, the exact anatomic locations of atherosclerotic lesions and the flow patterns at such sites in left and right human coronary arteries were studied in detail by flow visualization and high-speed cinemicrographic techniques using five isolated, transparent human coronary arterial trees prepared postmortem. It was found that atherosclerotic plaques and wall thickenings in left and right coronary arteries were localized almost exclusively on the outer wall of one or both daughter vessels at major bifurcations and T-junctions, which left the flow-divider free of lesions, and along the inner wall of curved segments. When flow patterns in such vessels were studied in detail, it was discovered that these sites were where flow was either slow or disturbed with the formation of slow recirculation and secondary flows and where wall shear stress was low. The results indicate that the major hemodynamic factors directly related to the localization of atherosclerotic plaques and wall thickenings in the human arterial system are the low fluid velocity and the resultant low shear stress that acts on the vessel wall.

Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries.

The localization of atherosclerosis in the coronary arteries may be governed by local hemodynamic features. In this study, the pulsatile hemodynamics of the left coronary artery bifurcation was numerically simulated using the spectral element method for realistic in vivo anatomic and physiologic conditions. The velocity profiles were found to be skewed in both the left anterior descending and the circumflex coronary arteries. Velocity skewing arose from the bifurcation as well as from the curvature of the artery over the myocardial surface. Arterial wall shear stress was significantly lower in the bifurcation region, including the side walls. The greatest oscillatory behavior was localized to the outer wall of the circumflex artery. The time-averaged mean wall shear stress varied from about 3 to 98 dynes/cm 2 in the left coronary artery system. The highly localized distribution of low and oscillatory shear stress along the walls strongly correlates with the focal locations of atheroma in the human left coronary artery.

Pulsatile flow in the human left coronary artery bifurcation: average conditions.

The hemodynamics of heart valve prostheses can be reproducibly investigated in vitro within circulatory mock loops. By measuring the downstream velocity and shear stress fields the shear stresses which are clinically responsible for damage to platelets and red blood cells can be determined.The mechanisms of damage and the effects of shear stresses on blood corpuscles were investigated by Wurzinger et al. (3, 4) at the Aerodynamics Institute of the RWTH Aachen. In the present study, the above data are incorporated into a mathematical correlation, which serves as a basic model for the estimation of blood damage.This mathematical model was applied to in vitro investigations of 25 different aortic valve prostheses. The results were compared to clinical findings. In most cases agreement was good, indicating that this model may be directly applied to the clinical situation. This new method facilitates the estimation of clinically expected blood damage from in vitro measurements. It may be useful for the develop...

Estimation of shear stress-related blood damage in heart valve prostheses--in vitro comparison of 25 aortic valves.

Knowledge of human blood-flow waveforms is required for in vitro investigations and numerical modelling. Parameters of interest include: velocity and flow waveform shapes, inter- and intra-subject variability and frequency content. We characterized the blood-velocity waveforms in the left and right common carotid arteries (CCAs) of 17 normal volunteers (24 to 34 years), analysing 3560 cardiac cycles in total. Instantaneous peak-velocity (Vpeak) measurements were obtained using pulsed-Doppler ultrasound with simultaneous collection of ECG data. An archetypal Vpeak waveform was created using velocity and timing parameters at waveform feature points. We report the following timing (post-R-wave) and peak-velocity parameters: cardiac interbeat interval (T(RR)) = 0.917 s (intra-subject standard deviation = +/- 0.045 s); cycle-averaged peak-velocity (V(CYC)) = 38.8 cm s(-1) (+/-1.5 cm s(-1)); maximum systolic Vpeak = 108.2 cm s(-1) (+/-3.8 cm s(-1)) at 0.152 s (+/-0.008 s); dicrotic notch Vpeak = 19.4 cm s(-1) (+/-2.9 cm s(-1)) at 0.398 s (+/-0.007 s). Frequency components below 12 Hz constituted 95% of the amplitude spectrum. Flow waveforms were computed from Vpeak by analytical solution of Womersley flow conditions (derived mean flow = 6.0 ml s(-1)). We propose that realistic, pseudo-random flow waveform sequences can be generated for experimental studies by varying, from cycle to cycle, only T(RR) and V(CYC) of a single archetypal waveform.

https://iopscience.iop.org/article/10.1088/0967-3334/20/3/301/pdf

Characterization of common carotid artery blood-flow waveforms in normal human subjects

A model for platelet activation based on the theory of damage, incorporating cumulative effects of stress history and past damage (senescence) was applied to a three-dimensional (3-D) model of blood flow through a St. Jude Medical (SJM) bileaflet mechanical heart valve (MHV), simulating flow conditions after implantation. The calculations used unsteady Reynolds-averaged Navier-Stokes formulation with non-Newtonian blood properties. The results were used to predict platelet damage from total stress (shear, turbulent, deformation), and incorporate the contribution of repeated passages of the platelets along pertinent trajectories. Trajectories that exposed the platelets to elevated levels of stress around the MHV leaflets and led them to entrapment within the complex 3-D vortical structures in the wake of the valve significantly enhanced platelet activation. This damage accumulation model can be used to quantify the thrombogenic potential of implantable cardiovascular devices, and indicate the problem areas of the device for improving their designs.

Flow-induced platelet activation and damage accumulation in a mechanical heart valve: numerical studies.

The specific features of turbulent flow that are likely to be damaging to the blood cells and platelets are the stresses which are intrinsic to turbulence, known as Reynolds stresses. These include normal stresses as well as shear stresses. The purpose of this study is to determine the magnitude of the turbulent stresses that may occur during ejection in the vicinity of normal and diseased aortic valves near normal pulmonary valves. Both Reynolds normal stresses and Reynolds shear stresses were calculated from velocities obtained in vitro with a laser Doppler anemometer in the region of two severely stenotic and regurgitant human aortic valves. Reynolds normal stresses were also calculated from velocities obtained with a hot-film anemometer in 21 patients in the region of normal and diseased aortic valves. In seven of these patients, it was calculated in the region of the normal pulmonary valve. The Reynolds normal stress in patients with combined aortic stenosis and insufficiency was prominently higher than in patients with normal valves. In the former, the Reynolds normal stress during ejection transiently reached 18,000 dynes/cm2. This was in the range of the Reynolds normal stress observed in vitro. The Reynolds shear stress measured in vitro transiently reached 11,900 dynes/cm2 during ejection. Because the Reynolds normal stresses in the presence of the severely stenotic and regurgitant valves were comparable in vitro and in patients, it is likely that the Reynolds shear stress in patients is also comparable to values measured in vitro. These values were well above the stresses which, when sustained, have been shown to have a damaging effect upon blood cells and platelets.

Turbulent stresses in the region of aortic and pulmonary valves.

The purpose of this investigation is to describe our preliminary observations of the overall pattern of flow in a mold of the left coronary artery of a pig. Flow in the coronary mold was visualized by the injection of dye into the sinus of Valsalva. Studies were performed during steady flow at rates of 100, 200, 300, 400, and 500 mL/min. Studies were also performed during pulsatile flow, using a pulse duplicator that simulated the magnitude and phasic pattern of coronary flow at rest and during reactive hyperemia. At conditions that simulated rest, mean coronary flow was adjusted to 121 mL/min of which 24 mL/min (20 percent) was systolic. During simulated reactive hyperemia, mean flow was 440 mL/min. Visualization of flow revealed the absence of disturbances of turbulence during both steady and pulsatile flow in the left anterior descending (LAD) and left circumflex (CIRC) coronary arteries throughout the entire range of flow studied. Prominent spiraling of flow occurred during steady and pulsatile flow. Spiraling of flow was not observed in the LAD at rest during pulsatile flow, but developed during simulated reactive hyperemia. Helical flows were observed in the CIRC both during simulated rest and reactive hyperemia. These observations suggest that helical flows may be characteristic features of flow in the left coronary artery; whereas turbulence may not be a feature of this flow field. Whether the spiraling of flow that we observed related to the spiral distribution of early atheroma reported by others, is undetermined.

Patterns of Flow in the Left Coronary Artery

Velocity profiles in symmetrically branched tubes simulating the aortic bifurcation

A comparison was made between turbulence calculated by subtracting an ensemble average from the instantaneous velocity and calculations made with a high pass digital filter. Velocity was measured with a laser Doppler anemometer in vitro in the region of a normal porcine aortic valve and in patients with a hot film anemometer in the region of normal aortic valves. From the velocity obtained in patients, the absolute turbulence intensity calculated using an ensemble average of 50 beats was nearly twice the turbulence intensity calculated using a digital filter. Individual beats sometimes showed differences of 150% compared to calculations based upon the use of a digital filter. Inspection showed that the ensemble average varied widely from the actual nonfluctuating velocity. Studies in vitro showed less beat to beat variation than occurred in patients. The absolute turbulence intensity measured in vitro, when calculated using an ensemble average, was only 20% greater than calculations using a digital filter. The differences were due primarily to beat-to-beat variations of the nonfluctuating velocity, but these beat-to-beat variations were less prominent than occurred in patients. These observations suggest that ensemble averaging may not be appropriate for the calculation of turbulence, particularly in patients.

F. J. Walburn

Papers

Turbulent stresses in the region of aortic and pulmonary valves.

Patterns of Flow in the Left Coronary Artery

Velocity profiles in symmetrically branched tubes simulating the aortic bifurcation

An experimental evaluation of the use of an ensemble average for the calculation of turbulence in pulsatile flow

Effect of the branch-to-trunk area ratio on the transition to turbulent flow: implications in the cardiovascular system.