Real-time pressure-volume diagrams for the evaluation of ventricular function

Using three intraventricular diameter signals obtained from ultrasonic distance gauges and applying the general ellipsoid model to the left ventricle, it was possible to obtain the left ventricular volume signal Implanting a miniature transducer in the left ventricle the pressure signal was attained. With these two signals the pressure-volume diagrams were constructed on line, and ventricular function during load manoeuvres could be studied from them. Because the whole process was done on line, using a microcomputer, the performance of the left ventricle to load manoeuvres in different conditions could be seen instantly.     

Muscular Subaortic Stenosis: The Initial Left Ventricular Inflow Tract Pressure as Evidence of Outflow Tract Obstruction

Two types of intraventricular pressure differences within the left ventricle of man are described. The first is encountered in cases of muscular (or fibrous) subaortic stenosis, in which the outflow tract pressure distal to the stenosis (and proximal to the aortic valve) is low, whereas all pressures recorded in the left ventricle proximal to the stenosis, including that just inside the mitral valve (the initial inflow tract pressure) are high.The second type of intraventricular pressure difference may be recorded in patients without muscular subaortic stenosis when a heart catheter is advanced to the left ventricular wall in such a manner that it becomes imbedded or entrapped by cardiac muscle in systole. Such an entrapped catheter records a high intraventricular pressure that is believed to reflect intramyocardial tissue pressure, which normally exceeds intracavitary pressure. In such cases the initial inflow tract pressure is not high and is precisely equal to the outflow tract systolic pressure, i.e. both are recording intracavity pressure. This type of intramyocardial to intracavitary pressure difference may also be encountered in the left ventricle of dogs.The recent suggestion that intraventricular pressure differences in the left ventricle of cases of muscular subaortic stenosis are due to catheter entrapment by cardiac muscle is refuted by using the initial inflow tract pressure as the means of differentiation between the two types of intraventricular pressure differences outlined.     

Patient-specific CFD models for intraventricular flow analysis from 3D ultrasound imaging: Comparison of three clinical cases

BackgroundAs the intracardiac flow field is affected by changes in shape and motility of the heart, intraventricular flow features can provide diagnostic indications. Ventricular flow patterns differ depending on the cardiac condition and the exploration of different clinical cases can provide insights into how flow fields alter in different pathologies.MethodsIn this study, we applied a patient-specific computational fluid dynamics model of the left ventricle and mitral valve, with prescribed moving boundaries based on transesophageal ultrasound images for three cardiac pathologies, to verify the abnormal flow patterns in impaired hearts. One case (P1) had normal ejection fraction but low stroke volume and cardiac output, P2 showed low stroke volume and reduced ejection fraction, P3 had a dilated ventricle and reduced ejection fraction.ResultsThe shape of the ventricle and mitral valve, together with the pathology influence the flow field in the left ventricle, leading to distinct flow features. Of particular interest is the pattern of the vortex formation and evolution, influenced by the valvular orifice and the ventricular shape. The base-to-apex pressure difference of maximum 2 mmHg is consistent with reported data.ConclusionWe used a CFD model with prescribed boundary motion to describe the intraventricular flow field in three patients with impaired diastolic function. The calculated intraventricular flow dynamics are consistent with the diagnostic patient records and highlight the differences between the different cases. The integration of clinical images and computational techniques, therefore, allows for a deeper investigation intraventricular hemodynamics in patho-physiology.     

Effect of ectopic excitation on the ventricular pump function in chicken

The pump function of the heart ventricles was studied in chest-open anaesthetized adult female chickens under sinus rhythm and ectopic excitation of different localization. The intraventricular pressure in the right and left heart ventricles was measured by insertion of catheters through the ventricular free walls. Maximum systolic pressure, end-diastolic pressure, contractility (dP/dtmax) and relaxation (dP/dtmin) of both heart ventricles, and duration of the asynchronous contraction time of the left ventricle were analyzed. It was revealed that reduction of the pump function of the left ventricle tends to be greater under right ventricular ectopic excitation compared with left ventricular one. In comparison with the sinus rhythm, the pump function of the right ventricle was preserved to a greater extent under stimulation of the left ventricular apex and was significantly impaired under right ventricular ectopic excitation. Relaxation of both heart ventricles was more susceptible to ventricular ectopic excitation than contractility, and was more vulnerable in the right ventricle than in the left one. The direction of changes of the pump function of the heart ventricles in chickens under ventricular ectopic excitation was similar to changes of the pump function of mammalian hearts.     

Computational modeling of the mechanical behavior of the cerebrospinal fluid system

A computational fluid dynamics (CFD) model of the cerebrospinal fluid system was constructed based on a simplified geometry of the brain ventricles and their connecting pathways. The flow is driven by a prescribed sinusoidal motion of the third ventricle lateral walls, with all other boundaries being rigid. The pressure propagation between the third and lateral ventricles was examined and compared to data obtained from a similar geometry with a stenosed aqueduct. It could be shown that the pressure amplitude in the lateral ventricles increases in the presence of aqueduct stenosis. No difference in phase shift between the motion of the third ventricle walls and the pressure in the lateral ventricles because of the aqueduct stenosis could be observed. It is deduced that CFD can be used to analyze the pressure propagation and its phase shift relative to the ventricle wall motion. It is further deduced that only models that take into account the coupling between ventricles, which feature a representation of the original geometry that is as accurate as possible and which represent the ventricle boundary motion realistically, should be used to make quantitative statements on flow and pressure in the ventricular space.     

Incremental elastic modulus for ventricles in diastole

Utilizing the formulation of so-called 'small deformations superimposed on a large initial deformation' the incremental pressure modulus of a ventricle in diastole is studied and the explicit expression of it is obtained as a function of intraventricular pressure. In the analysis the ventricular wall material is assumed to be homogeneous, incompressible, isotropic and the stress-strain relation is exponential. The numerical results for a dog left ventricle indicate that above a critical value of inner pressure the incremental pressure modulus increases with increasing intra-ventricular pressure. Furthermore, the relationship between the stiffness and pressure is seen to be curvilinear (particularly for low pressure level), but for large values of inner pressure the behavior of the curve may be approximated by a set of straight lines.     

A rhesus monkey model for continuous infusion of drugs into cerebrospinal fluid

A new rhesus monkey model with two intraventricular catheter systems was developed to examine the pharmacokinetics and neurotoxicity of chemotherapeutic agents administered by continuous intraventricular infusion. A lateral ventricular catheter system implanted in the lateral ventricle and attached to a subcutaneous access port on the animal's back is used for infusion of drugs into the ventricle. A Pudenz catheter implanted in the fourth ventricle and connected to a subcutaneous Ommaya reservoir permits repetitive CSF sampling in unanesthetized animals. The model was evaluated in five animals for over 12 months for catheter patency, surgical complications, and utility in studying the pharmacokinetics of continuous intraventricular infusion of methotrexate. There were no perioperative complications. Three of the five monkeys maintained both systems successfully. The other two animals developed staphylococcal ventriculitis, one at 7 days as a result of manipulation of the incision by the animal leading to cellulitis around the catheter site and subsequent ventriculitis, the other at 5 months. Both animals were treated successfully with antibiotics and catheter removal. An infusion of 0.05 mg of methotrexate over 24 hours maintained ventricular drug concentrations of 1 mol/L without evidence of neurotoxicity. This new model has applications both for the development of continuous intraventricular infusion as a therapeutic approach for the treatment of meningeal cancers in humans and as a research tool to study the distribution and elimination of drugs from the CSF.     

RV instantaneous intraventricular diastolic pressure and velocity distributions in normal and volume overload awake dog disease models

Intraventricular diastolic right ventricular (RV) flow field dynamics were studied by functional imaging using three-dimensional (3D) real-time echocardiography with sonomicrometry and computational fluid dynamics in seven awake dogs at control with normal wall motion (NWM) and RV volume overload with diastolic paradoxical septal motion. Burgeoning flow cross section between inflow anulus and chamber walls induces a convective pressure rise, which represents a "convective deceleration load" (CDL). High spatiotemporal resolution dynamic pressure and velocity distributions of the intraventricular RV flow field revealed time-dependent, subtle interactions between intraventricular local acceleration and convective pressure gradients. During the E-wave upstroke, the total pressure gradient along intraventricular flow is the algebraic sum of a pressure decrease contributed by local acceleration and a pressure rise contributed by a convective deceleration that partially counterbalances the local acceleration gradient. This underlies the smallness of early diastolic intraventricular gradients. At peak volumetric inflow, local acceleration vanishes and the total adverse intraventricular gradient is convective. During the E-wave downstroke, the strongly adverse gradient embodies the streamwise pressure augmentations from both local and convective decelerations. It induces flow separation and large-scale vortical motions, stronger in NWM. Their dynamic corollaries on intraventricular pressure and velocity distributions were ascertained. In the NWM pattern, the strong ring-like vortex surrounding the central core encroaches on the area available for flow toward the apex. This results in higher linear velocities later in the downstroke of the E wave than at peak inflow rate. The augmentation of CDL by ventriculoannular disproportion may contribute to E wave and E-to-A ratio depression with chamber dilatation.     

The effects of the interthalamic adhesion position on cerebrospinal fluid dynamics in the cerebral ventricles

The interthalamic adhesion is a unique feature of the third ventricle in the brain. It differs in shape and size and its location varies between individuals. In this study, computational fluid dynamics was performed on 4 three-dimensional models of the cerebral ventricular system with the interthalamic adhesion modeled in different locations in the third ventricle. Cerebrospinal fluid (CSF) was modeled as incompressible Newtonian fluid and flow was assumed laminar. The periodic motion of CSF flow as a function of the cardiac cycle starting from diastole was prescribed as the inlet boundary condition at the foramen of Monroe. Results from this study show how the location of the interthalamic adhesion influences the pattern of pressure distribution in the cerebral ventricles. In addition, the highest CSF pressure in the third ventricle can vary by ～50% depending on the location of the interthalamic adhesion. We suggest that the interthalamic adhesion may have functional implications on the development of hydrocephalus and it is important to model this anatomical feature in future studies.     

FSI simulation of asymmetric mitral valve dynamics during diastolic filling

In this article, we present a fluid-structure interaction algorithm accounting for the mutual interaction between two rigid bodies. The algorithm was used to perform a numerical simulation of mitral valve (MV) dynamics during diastolic filling. In numerical simulations of intraventricular flow and MV motion, the asymmetry of the leaflets is often neglected. In this study the MV was rendered as two rigid, asymmetric leaflets. The 2D simulations incorporated the dynamic interaction of blood flow and leaflet motion and an imposed subject-specific, transient left ventricular wall movement obtained from ultrasound recordings. By including the full Jacobian matrix in the algorithm, the speed of the simulation was enhanced by more than 20% compared to using a diagonal Jacobian matrix. Furthermore, our results indicate that important features of the flow field may not be predicted by the use of symmetric leaflets or in the absence of an adequate model for the left atrium.     

丹酚酸B对大鼠离体工作心脏血流动力学的影响

目的 研究丹酚酸B对离体大鼠工作心脏血流动力学的影响.方法 采用Langendorff离体心脏灌流的方法,以左室内压( LVSP)、左室舒末压(LVEDP)、室内压最大上升速率(+dp/dtmax)、室内压最大下降速率(- dp/dtmax)、心率(HR)等血流动力学参数为指标,观察丹酚酸B对心肌收缩性能的影响.结果 不同剂量(10、5、2.5 mg/L)的丹酚酸B可使LVSP、±dp/dtmax明显升高,同时使HR减慢,并呈剂量依赖性,但对LVEDP无明显作用.结论 丹酚酸B对离体工作心脏有剂量依赖性正性肌力作用.     

An elongation model of left ventricle deformation in diastole

A numerical method of the left ventricle (LV) deformation, an elongation model, was put forth for the study of LV fluid mechanics in diastole. The LV elongated only along the apical axis, and the motion was controlled by the intraventricular flow rate. Two other LV models, a fixed control volume model and a dilation model, were also used for model comparison and the study of LV fluid mechanics. For clinical sphere indices (SIs, between 1.0 and 2.0), the three models showed little difference in pressure and velocity distributions along the apical axis at E-peak. The energy dissipation was lower at a larger SI in that the jet and vortex development was less limited by the LV cavity in the apical direction. LV deformation of apical elongation may represent the primary feature of LV deformation in comparison with the secondary radial expansion. The elongation model of the LV deformation with an appropriate SI is a reasonable, simple method to study LV fluid mechanics in diastole.     

Sodium deficiency enhances the behavioral responses to centrally administered vasopressin in rats

The ability of sodium deficiency to stimulate vasopressin (VP) release was examined by determining if sodium deficiency sensitizes the animal to the behavioral disruption caused by intraventricular injections of VP. In sodium-replete rats, intraventricular injections of 50 ng VP on Day 1 had no effect on behavior, but this dose elicited abnormal behaviors (barrel rolls, hind-limb extensions) when administered on Day 2, indicating a sensitization phenomenon. In separate experiments, the first intraventricular injection of 50 ng VP in sodium-deficient but not in sodium-replete rats also elicited barrel rotations followed by hind-limb extension. Intraventricular injection of VP also disrupted motor behavior in sodium-replete rats that had multiple prior experiences with sodium deficiency but not in naive rats. These results show that sodium deficiency can mimic the effect of central injections of VP in sensitizing the brain to the behavioral effects of exogenous VP. This suggests that sodium deficiency induces the central release of VP.     

Sudden interruption of leaflet opening by ventricular contractions: a mechanism of mitral regurgitation.

The motion of both mitral cusps and the presence of valvular regurgitation during ventricular contractions were investigated in seven experiments on dogs in which radiopaque markers had been sutured to the cusps and the valve annulus 1-32 wk before the studies. Cineangiograms of the left ventricle were obtained during ventricular ectopic beats, interposed throughout the cardiac cycle (20-99% of cycle length) and during induced variations in the P-R interval (0-200 ms). Mitral regurgitation was observed only during a) weak, early ectopic beats (peak pressure below 34 mmHg) which were incapable of closing the cusps and b) when ventricular contractions suddenly interrupted normal leaflet motion toward the ventricle, during three well-defined periods of diastole (diastolic valve opening, diastolic rebound, and atrial opening). Valve closure following sudden reversal of cusp opening was slow and the leaflets often did not arrive simultaneously at their closed positions. These findings suggest that sudden interruption of leaflet opening by ventricular contractions is an important mechanism of transient mitral regurgitation in the normal heart.     

A Tissue-Level Electromechanical Model of the Left Ventricle: Application to the Analysis of Intraventricular Pressure

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain.     

Numerical Modeling of Intraventricular Flow during Diastole after Implantation of BMHV

This work presents a numerical simulation of intraventricular flow after the implantation of a bileaflet mechanical heart valve at the mitral position. The left ventricle was simplified conceptually as a truncated prolate spheroid and its motion was prescribed based on that of a healthy subject. The rigid leaflet rotation was driven by the transmitral flow and hence the leaflet dynamics were solved using fluid-structure interaction approach. The simulation results showed that the bileaflet mechanical heart valve at the mitral position behaved similarly to that at the aortic position. Sudden area expansion near the aortic root initiated a clockwise anterior vortex, and the continuous injection of flow through the orifice resulted in further growth of the anterior vortex during diastole, which dominated the intraventricular flow. This flow feature is beneficial to preserving the flow momentum and redirecting the blood flow towards the aortic valve. To the best of our knowledge, this is the first attempt to numerically model intraventricular flow with the mechanical heart valve incorporated at the mitral position using a fluid-structure interaction approach. This study facilitates future patient-specific studies.     

Towards a biomechanics-based technique for assessing myocardial contractility: an inverse problem approach

This work presents the initial development and implementation of a novel 3D biomechanics-based approach to measure the mechanical activity of myocardial tissue, as a potential non-invasive tool to assess myocardial function. This technique quantifies the myocardial contraction forces developed within the ventricular myofibers in response to electro-physiological stimuli. We provide a 3D finite element formulation of a contraction force reconstruction algorithm, along with its implementation using magnetic resonance (MR) data. Our algorithm is based on an inverse problem solution governed by the fundamental continuum mechanics principle of conservation of linear momentum, under a first-order approximation of elastic and isotropic material conditions. We implemented our technique using a subject-specific ventricle model obtained by extracting the left ventricular anatomical features from a set of high-resolution cardiac MR images acquired throughout the cardiac cycle using prospective electrocardiographic gating. Cardiac motion information was extracted by non-rigid registration of the mid-diastole reference image to the remaining images of a 4D dataset. Using our technique, we reconstructed dynamic maps that show the contraction force distribution superimposed onto the deformed ventricle model at each acquired frame in the cardiac cycle. Our next objective will consist of validating this technique by showing the correlation between the presence of low contraction force patterns and poor myocardial functionality.     

Fluid Dynamics of Ventricular Filling in the Embryonic Heart

The vertebrate embryonic heart first forms as a valveless tube that pumps blood using waves of contraction. As the heart develops, the atrium and ventricle bulge out from the heart tube, and valves begin to form through the expansion of the endocardial cushions. As a result of changes in geometry, conduction velocities, and material properties of the heart wall, the fluid dynamics and resulting spatial patterns of shear stress and transmural pressure change dramatically. Recent work suggests that these transitions are significant because fluid forces acting on the cardiac walls, as well as the activity of myocardial cells that drive the flow, are necessary for correct chamber and valve morphogenesis. In this article, computational fluid dynamics was used to explore how spatial distributions of the normal forces acting on the heart wall change as the endocardial cushions grow and as the cardiac wall increases in stiffness. The immersed boundary method was used to simulate the fluid-moving boundary problem of the cardiac wall driving the motion of the blood in a simplified model of a two-dimensional heart. The normal forces acting on the heart walls increased during the period of one atrial contraction because inertial forces are negligible and the ventricular walls must be stretched during filling. Furthermore, the force required to fill the ventricle increased as the stiffness of the ventricular wall was increased. Increased endocardial cushion height also drastically increased the force necessary to contract the ventricle. Finally, flow in the moving boundary model was compared to flow through immobile rigid chambers, and the forces acting normal to the walls were substantially different.     

Motion of both mitral valve leaflets: a cineroentgenographic study in intact dogs.

Motion and position of both mitral leaflets were studied in five normal dogs 1-11 wk after radiopaque markers were sutured on the valve cusps and on the mitral annulus. Cinefluorograms and cineangiograms (100-120 frames/s) of left atrium and left ventricle were used to study cusp motion and intraventricular flow patterns, and to detect mitral regurgitation during sinus rhythm (42-184 beats/min) and during isolated atrial or ventricular contractions. Time-motion of both leaflets was similar throughout diastole with the exception of delayed posterior cusp opening. Peak opening and closing speeds, opening and closing times, and time of complete closure, measured from the Q wave of the ECG, were not significantly affected by the variations in heart rate. Diastolic leaflet closure began immediately after opening, while the ventricular cavity was small, and was caused by flow eddies behind the cusps. Isolated ventricular contractions closed the valve leaflets completely and symmetric valve closure was ensured by the different rates of leaflet edge approximation. In contrast, atrial closure was slow, partial, and of very short duration.     

On the mechanisms of coupling in adrenaline-induced bigeminy in sensitized hearts.

The mechanism of coupling in adrenaline-induced ventricular bigeminy in sensitized hearts has been investigated in intact animals, isolated preparations, and single cardiac fibers. The electrophysiological and cardiovascular dynamic changes during the development of fixed interval coupling strongly indicate that the coupled beats result from stretch of subsidiary pacemaker fibers in the specialized ventricular conduction system, induced by the mechanical response to the normally conducted sinus impulse. The resulting intraventricular pressure elicits an extrasystole when a certain critical end systolic pressure for a particular animal is reached. The interval between the normal and premature ventricular beat decreases progressively as the intraventricular pressure rises, as a result of the combined action of adrenaline and postextrasystolic potentiation. The onset of ventricular bigeminy is preceded by a shift in the pacemaker site to the A-V junctional area, due to a differential effect of the anesthetic-adrenaline combination on fibers of the S-A node and those in the junctional area. The degree of prematurity of the coupled beat shows an inverse linear relationship to the intraventricular pressure of the initiating beat at the end of systole. The premature QRS complex occurs after a period of mechano-electrical latency, the duration of which is directly related to this pressure.