Extracorporeal circulation during on-pump cardiac surgery: An evaluation of the energy equivalent pressure index based on waveforms decomposition in harmonics.

The use of pulsatile perfusion instead of nonpulsatile perfusion during cardiopulmonary bypass continues to be a source of debate. The disagreements among the conclusions of the published studies may be due to different factors: differences in the type of patients included in the studies, differences in the protocol of the studies, and difficulty to quantify the pulsatility of the flow. In the present paper, we propose a quantitative evaluation of Shepard's energy equivalent pressure index, based on the harmonic decomposition of the physiological aortic pressure and flow rate signal. It is thus demonstrated that the surplus energy provided by pulsatile flow remains moderate (of order 10 mm Hg), but that it can be improved by changing the relative shapes of the pressure and flow waves.

Fluid dynamics characterisation of a rotating bioreactor for tissue engineering.

Biological scaffolds composed of extracellular matrix (ECM) derived from decellularised tissue are increasingly used in regenerative medicine. In this project, a flow perfusion bioreactor (the rotary cell culture system (RCCS), commercially available from Synthecon (Houston, TX)) is used in order to obtain some esophageal extracellular matrix. A theoretical mechanical characterisation of this experimental set-up is provided. Due to the combination of rotation and perfusion, some spiral Poiseuille flow is created inside the tubular esophagus. In a transverse section, a particle (or cell) experiences simultaneously gravitational, Archimedes, centrifugal, Coriolis, and drag forces. In a frame of reference rotating with angular velocity ω, the particle follows a periodic nearly circular path in the clockwise direction, associated with a very slow centrifugal drift towards the esophagus wall. It appears that moderate perfusion rate and rotation speed (ω < 20 rpm and Q < 30 ml/min) are appropriate experimental conditions for esophagus tissue engineering using the RCCS Synthecon bioreactor.

Morphological analysis of tumor cell/endothelial cell interactions under shear flow.

In the process of hematogenous cancer metastasis, tumor cells (TCs) must shed into the blood stream, survive in the blood circulation, migrate through the vascular endothelium (extravasation) and proliferate in the target organs. However, the precise mechanisms by which TCs penetrate the endothelial cell (EC) junctions remain one of the least understood aspects of TC extravasation. This question has generally been addressed under static conditions, despite the important role of flow induced mechanical stress on the circulating cell-endothelium interactions. Moreover, flow studies were generally focused on transient or firm adhesion steps of TC-EC interactions and did not consider TCs spreading or extravasation. In this paper, we used a parallel-plate flow chamber to investigate TC-EC interactions under flow conditions. An EC monolayer was cultured on the lower plate of the flow chamber to model the endothelial barrier. Circulating TCs were introduced into the flow channel under a well-defined flow field and TC cell shape changes on the EC monolayer were followed in vitro with live phase contrast and fluorescence microscopy. Two spreading patterns were observed: radial spreading which corresponds to TC extravasation, and axial spreading where TCs formed a mosaic TC-EC monolayer. By investigating the changes in area and minor/major aspect ratio, we have established a simple quantitative basis for comparing spreading modes under various shear stresses. Contrary to radial spreading, the extent of axial spreading was increased by shear stress.

Collateral blood flow between left coronary artery bypass grafts and chronically occluded right coronary circulation in patients with triple vessel disease. Observations during complete revascularisation of beating hearts.

OBJECTIVE: Preoperative measurements of collateral blood flow in patients with triple vessel disease and chronic occlusions of the right coronary artery do not, currently, ascertain the need to revascularise an occluded right coronary artery. We performed direct measurements of flow across left coronary bypass grafts to determine their contributions to collateral blood flow. METHODS: Collateral blood flow was scored preoperatively according to Rentrop in 13 patients with triple vessel disease and chronic occlusions of the right coronary artery who underwent complete, off-pump, surgical revascularisation. The transit-time flow through the left coronary grafts was measured before and after unclamping of the right coronary artery bypass graft. RESULTS: Unclamping of the right coronary artery bypass graft was associated with a 5.9+/-6.9ml/min (mean+/-SD) decrease in flow across the left circumflex territory (P=0.009), which was proportional to the preoperative Rentrop score (P=0.007). No significant change was observed in flow across the graft to the left anterior descending artery. CONCLUSIONS: Grafts to the left circumflex system are the only grafts that supply a significant, albeit modest amount of collateral blood flow to chronically occluded right coronary artery. These observations confirm that (1) most collateral flow after revascularisation is supplied by the native network, and (2) revascularisation of an occluded right coronary artery is fully justified.

Use of Cell Transit Analyser pulse height to study the deformation of erythrocytes in microchannels.

Information on microvascular rheology can be used to develop mathematical models of network hemodynamics in various contexts: tumor-induced angiogenesis, reaction to ischemia and collateralization, hypertension, ... The rheological method which probably most closely simulates red blood cell (RBC) flow behavior in the microcirculation is the determination of individual erythrocyte transit time and shape changes during flow through cylindrical micropores. However, these filtration experiments remain difficult to interpret in terms of cell flow properties, because the shape of the cell inside the pore is unknown. This paper uses the cell transit analyser (CTA) electrical pulse (especially the pulse height) to determine the relationship between the cell velocity and deformed shape in the pore, depending on the flow strength, suspending medium viscosity and cell membrane elasticity. As predicted by published numerical simulations for the flow of deformable particles through narrow channels, increasing pressure leads to increased deformation, but for a given pressure, increased viscosity leads to a slight increase in deformation. The sensitivity of filtration experiments to cell mechanical properties is improved when using low driving pressures and narrow and sufficiently long pores.

Sensitivity analysis and parameter estimation of a coronary circulation model for triple-vessel disease.

Mathematical models of the coronary circulation have been shown to provide useful information for the analysis of intracoronary blood flow and pressure measurements acquired during coronary artery bypass graft (CABG) surgery. Although some efforts towards the patient-specific estimation of model parameters have been presented in this context, they are based on simplifying hypotheses about the collateral circulation and do not take advantage of the whole set of data acquired during CABG. In order to overcome these limitations, this paper presents an exhaustive parameter sensitivity analysis and a multiobjective patient-specific parameter estimation method, applied to a model of the coronary circulation of patients with triple vessel disease. The results of the sensitivity analysis highlighted the importance of capillary and collateral development. On the other hand, the estimation method was applied to intraoperative clinical data from ten patients obtained during CABG, which permitted to assess patient-specific collateral vessel situations. These approaches provide new insights regarding the heterogeneous configuration of the collateral circulation.

Theoretical study of the flow rate toward the right heart territory in case of total occlusion of the right coronary artery.

In this work, patients with severe coronary disease and chronic occlusion of the right coronary artery (RCA) are studied. In this clinical situation, the collateral circulation is an important factor in the preservation of the myocardium until reperfusion of the area at risk. An accurate estimation of collateral flow is crucial in surgical bypass planning as it can influence the outcome of a given treatment for a given patient. The evaluation of collateral flow is frequently achieved using an index (CFI, Collateral Flow Index) based on pressure measurements. Using a model of the coronary circulation based on hydraulic/electric analogy, we demonstrate, through theoretical simulations, that a wide range of fractional collateral flow values can be obtained for any given distal pressure difference depending on the values of the capillary and collateral resistances.

Multiobjective patient-specific estimation of a coronary circulation model for triple vessel disease.

Computational models can help understand the hemodynamics of the coronary circulation, which is of the upmost importance to help clinicians before, during and after a coronary artery bypass graft surgery. In this paper, we propose a multiobjective optimization method for parameter estimation of a computational model representing the coronary circulation on patients with a triple vessel disease. This estimation was not based on any assumption regarding the development of the collateral circulation, like in previous works. Indeed, the collateral development of a given patient is estimated through the model parameters. Parameter estimation was performed using clinical data from three patients, obtained before and during an off-pump coronary artery bypass graft surgery (CABG). Results showed a better performance when comparing the simulation with clinical data, since the total error estimation for three patients was reduced by 40 ± 22%. Moreover, the proposed method provides new insight regarding the heterogeneous configuration of the alternative collateral vessels.

MagnetoHemoDynamics in the aorta and electrocardiograms.

This paper addresses a complex multi-physical phenomenon involving cardiac electrophysiology and hemodynamics. The purpose is to model and simulate a phenomenon that has been observed in magnetic resonance imaging machines: in the presence of a strong magnetic field, the T-wave of the electrocardiogram (ECG) gets bigger, which may perturb ECG-gated imaging. This is due to a magnetohydrodynamic (MHD) effect occurring in the aorta. We reproduce this experimental observation through computer simulations on a realistic anatomy, and with a three-compartment model: inductionless MHD equations in the aorta, bi-domain equations in the heart and electrical diffusion in the rest of the body. These compartments are strongly coupled and solved using finite elements. Several benchmark tests are proposed to assess the numerical solutions and the validity of some modeling assumptions. Then, ECGs are simulated for a wide range of magnetic field intensities (from 0 to 20 T).

A more sensitive pressure-based index to estimate collateral blood supply in case of coronary three-vessel disease.

With progressive occlusion of a coronary main artery, some anastomotic vessels are recruited in order to supply blood to the ischemic region. This collateral circulation is an important factor in the preservation of the myocardium until reperfusion of the area at risk. An accurate estimation of collateral flow is crucial in surgical bypass planning as it alters the blood flow distribution in the coronary network and can influence the outcome of a given treatment for a given patient. The evaluation of collateral flow is frequently achieved using an index based on pressure measurements. It is named Collateral Flow Index (CFI) and defined as: (P(w)-P(v))/(P(ao)-P(v)), where P(w) is the pressure distal to the thrombosis, P(ao) the aortic pressure and P(v) the central venous pressure. We propose here another index, that is more sensitive to the P(w) value and could thus describe the role of collateral flow with more precision. We illustrate this idea using some clinical pressure measurements in patients with severe coronary disease (stenoses on the left branches and total occlusion of the right coronary artery).

Pulsed magnetohydrodynamic blood flow in a rigid vessel under physiological pressure gradient.

Blood flow in a steady magnetic field has been of great interest over recent years. Many researchers have examined the effects of magnetic fields on velocity profiles and arterial pressure, and major studies have focused on steady or sinusoidal flows. In this paper, we present a solution for pulsed magnetohydrodynamic blood flow with a somewhat realistic physiological pressure wave obtained using a Windkessel lumped model. A pressure gradient is derived along a rigid vessel placed at the output of a compliant module which receives the ventricle outflow. Then, velocity profile and flow rate expressions are derived in the rigid vessel in the presence of a steady transverse magnetic field. As expected, results showed flow retardation and flattening. The adaptability of our solution approach allowed a comparison with previously addressed flow cases and calculations presented a good coherence with those well established solutions.

Analog electrical model of the coronary circulation in case of multiple revascularizations.

In this work, we propose an analog electrical model of the coronary circulation for patients with obstructive disease undergoing revascularization. In this clinical situation, the collateral circulation to the occluded artery is difficult to ascertain via preoperative measurements and well-developed collaterals might induce long-term restenosis of the revascularized artery due to flow competition mechanisms. The proposed model allows an original biomechanical analysis of per-operative hemodynamic data in order to assess quantitative evaluation of pressures and flows inside the native stenosed arteries, the collateral network and the bypass grafts. Average cardiac cycle values are analysed. In the case of 3-vessel disease and chronic occlusion of the right coronary artery, the quantitative results confirm the protective effects of the collateral flows in the pathological situation, but also show that the revascularization of the occluded right artery is fully justified since the collateral flows remain low, even when the left territory is revascularized. The model thus provides a computational tool to evaluate therapeutic strategies for each patient.

Cardiac and respiratory MRI gating using combined wavelet sub-band decomposition and adaptive filtering.

Cardiac Magnetic Resonance Imaging (MRI) requires synchronization to overcome motion related artifacts caused by the heart's contractions and the chest wall movements during respiration. Achieving good image quality necessitates combining cardiac and respiratory gating to produce, in real time, a trigger signal that sets off the consecutive image acquisitions. This guarantees that the data collection always starts at the same point of the cardiac cycle during the exhalation phase. In this paper, we present a real time algorithm for extracting a cardiac-respiratory trigger signal using only one, adequately placed, ECG sensor. First, an off-line calculation phase, based on wavelet decomposition, is run to compute an optimal QRS filter. This filter is used, afterwards, to accomplish R peak detection, while a low pass filtering process allows the retrieval of the respiration cycle. The algorithm's synchronization capabilities were assessed during mice cardiac MRI sessions employing three different imaging sequences, and three specific wavelet functions. The prominent image enhancement gave a good proof of correct triggering. QRS detection was almost flawless for all signals. As for the respiration cycle retrieval it was evaluated on contaminated simulated signals, which were artificially modulated to imitate respiration. The results were quite satisfactory.

Alterations in human ECG due to the MagnetoHydroDynamic effect: a method for accurate R peak detection in the presence of high MHD artifacts.

Blood flow in high static magnetic fields induces elevated voltages that contaminate the ECG signal which is recorded simultaneously during MRI scans for synchronization purposes. This is known as the magnetohydrodynamic (MHD) effect, it increases the amplitude of the T wave, thus hindering correct R peak detection. In this paper, we inspect the MHD induced alterations of human ECG signals recorded in a 1.5 Tesla steady magnetic field and establish a primary characterization of the induced changes using time and frequency domain analysis. We also reexamine our previously developed real time algorithm for MRI cardiac gating and determine that, with a minor modification, this algorithm is capable of achieving perfect detection even in the presence of strong MHD artifacts.

Collateral flow reserve and right coronary occlusion: evaluation during off-pump revascularization.

The aim of this study was the determination of the pressure-derived collateral fractional flow reserve (FFR(coll)) in patients with three vessel disease and chronic occlusion of the right coronary artery undergoing surgical complete revascularization with the off-pump technique. The angiograms of eight patients were preoperatively analysed to quantify collaterality. FFR(coll) was determined before any revascularization (FFR(coll) 0), and after revascularization of the left coronary arteries, (FFR(coll) 1). FFR(coll) 0 was compared to the Rentrop grade, to the left ventricular ejection fraction (LVEF), and to FFR(coll) 1. No correlation was demonstrated between preoperative Rentrop grade and FFR(coll) 0. There was a linear statistically significant correlation between FFR(coll) 0 and LVEF (P;ie0.001). No significant variation of the FFR(coll) index was observed after performing left coronary artery bypass grafts. Collaterality observed on the coronary angiogram cannot be used as an estimation of the functional collaterality, which can be better appreciated with the LVEF. The absence of variation of FFRcoll before and after left coronary artery revascularization suggests that grafting of the occluded right coronary artery remains justified.

A new flow chamber for the study of shear stress and transmural pressure upon cells adhering to a porous biomaterial.

Biomaterials used in some biomedical devices are porous and exposed to normal and tangential flow of biofluids. To examine the influence of flow induced forces on the morphology and the biochemical responses of cells adhering to such biomaterials, a Hele-Shaw cell with a porous bottom wall was designed and characterized experimentally. Theoretical predictions for the flow in the chamber are provided and allow to quantify the shear stress and/or transmural pressure exerted on cells. It is thus possible to follow up continuously the shape changes of cells that are adherent on a permeable membrane used in bioreactors.