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.     

IABP在瓣膜病合并巨大左心室患者中的临床应用

目的评价瓣膜病合并巨大左心室患者术后应用主动脉内球囊反搏泵(IABP)的效果.方法回顾分析本院1997～2000年瓣膜病合并巨大左心室换瓣术后应用IABP患者26例(组Ⅰ),对照组(组Ⅱ)为同期未应用IABP患者30例.观察其血流动力学、心功能、心律、ST段的,比较两组早期生存率.结果IABP辅助时间为(57±29)h,患者在应用IABP后,桡动脉压力在早期有所下降(P＜0.01);舒张压上升(P＜0.01);平均动脉压于应用后即可见明显提高,外周阻力明显降低.心律失常的变化于应用IABP后1 h频发室早或室速转为偶发室早,ST段的抬高或降低在30 min～1 h后恢复正常.组Ⅱ患者出现的频发室早或室速于(22±11)h后转为偶发室早,ST段的抬高或降低于(24±10)h后.持续左心功能(CCO)监测结果见组Ⅰ CO、CI于应用IABP后2 h明显恢复,24 h已经恢复到术前水平;组Ⅱ于24 h才有所恢复.组Ⅰ早期生存率为80.3%,与组Ⅱ(64.7%)比较P＜0.01.结论IABP能够有效地控制瓣膜病合并巨大左心室患者术后室性心律失常的发生,使心功能得到了有效的支持,大大降低了早期死亡率.     

Influence of dilated cardiomyopathy and a left ventricular assist device on vortex dynamics in the left ventricle

Together with new developments in mechanical cardiac support, the analysis of vortex dynamics in the left ventricle has become an increasingly important topic in literature. The aim of this study was to develop a method to investigate the influence of a left ventricular assist device (LVAD) on vortex dynamics in a failing ventricle. An axisymmetric fluid dynamics model of the left ventricle was developed and coupled to a lumped parameter model of the complete circulation. Simulations were performed for healthy conditions and dilated cardiomyopathy (DCM). Vortex structures in these simulations were analysed by means of automated detection. Results show that the strength of the leading vortex ring is lower in a DCM ventricle than in a healthy ventricle. The LVAD further influences the maximum strength of the vortex and also causes the vortex to disappear earlier in time with increasing LVAD flows. Understanding these phenomena by means of the method proposed in this study will contribute to enhanced diagnostics and monitoring during cardiac support.     

Different "weight" of cardiac and general adiposity in predicting left ventricle morphology

Excess adiposity has been widely related to cardiac morphological changes. Nevertheless, the mechanistic link between increased adiposity and left ventricular (LV) morphology is controversial and not completely understood. In this context, several authors have recently debated the different "weight" of BMI as an index of general adiposity vs. the importance of the epicardial fat depot as a marker of local visceral adiposity in obesity-related LV changes. Studies in uncomplicated obesity suggest that the role of BMI in predicting LV abnormalities remains rather doubtful. In contrast, several lines of evidence suggest that cardiac adiposity could play an important part in the development of cardiac modifications. Epicardial fat as an index of cardiac adiposity could have a functional and mechanical role in obesity-related LV abnormalities. Epicardial fat is clinically correlated with LV mass, atrial dimensions, and diastolic function, but a causal effect of epicardial adipose tissue on cardiac chamber modifications remains to be demonstrated. Nevertheless, the close anatomical and functional relationship of epicardial adipose tissue to the adjacent myocardium should readily allow local, paracrine interactions between these tissues.     

Numerical simulation of blood flow in the left ventricle and aortic sinus using magnetic resonance imaging and computational fluid dynamics

Understanding cardiac blood flow patterns has many applications in analysing haemodynamics and for the clinical assessment of heart function. In this study, numerical simulations of blood flow in a patient-specific anatomical model of the left ventricle (LV) and the aortic sinus are presented. The realistic 3D geometry of both LV and aortic sinus is extracted from the processing of magnetic resonance imaging (MRI). Furthermore, motion of inner walls of LV and aortic sinus is obtained from cine-MR image analysis and is used as a constraint to a numerical computational fluid dynamics (CFD) model based on the moving boundary approach. Arbitrary Lagrangian–Eulerian finite element method formulation is used for the numerical solution of the transient dynamic equations of the fluid domain. Simulation results include detailed flow characteristics such as velocity, pressure and wall shear stress for the whole domain. The aortic outflow is compared with data obtained by phase-contrast MRI. Good agreement was found between simulation results and these measurements.     

Segmentation of left ventricle in short-axis echocardiographic sequences by weighted radial edge filtering and adaptive recovery of dropout regions

In this paper, we present a weighted radial edge filtering algorithm with adaptive recovery of dropout regions for the semi-automatic delineation of endocardial contours in short-axis echocardiographic image sequences. The proposed algorithm requires minimal user intervention at the end diastolic frame of the image sequence for specifying the candidate points of the contour. The region of interest is identified by fitting an ellipse in the region defined by the specified points. Subsequently, the ellipse centre is used for originating the radial lines for filtering. A weighted radial edge filter is employed for the detection of edge points. The outliers are corrected by global as well as local statistics. Dropout regions are recovered by incorporating the important temporal information from the previous frame by means of recursive least squares adaptive filter. This ensures fairly accurate segmentation of the cardiac structures for further determination of the functional cardiac parameters. The proposed algorithm was applied to 10 data-sets over a full cardiac cycle and the results were validated by comparing computer-generated boundaries to those manually outlined by two experts using Hausdorff distance (HD) measure, radial mean square error (rmse) and contour similarity index. The rmse was 1.83 mm with a HD of 5.12 ± 1.21 mm. We have also compared our results with two existing approaches, level set and optical flow. The results indicate an improvement when compared with ground truth due to incorporation of temporal clues. The weighted radial edge filtering algorithm in conjunction with adaptive dropout recovery offers semi-automatic segmentation of heart chambers in 2D echocardiography sequences for accurate assessment of global left ventricular function to guide therapy and staging of the cardiovascular diseases.     

Jet collisions and vortex reversal in the human left ventricle

Unnatural dynamics of the notorious vortex in the left ventricle is often associated with cardiac disease. Understanding how different cardiac diseases alter the flow physics in the left ventricle may therefore provide a powerful tool for disease detection. In this work, the fluid dynamics in the left ventricle subject to different severities of aortic regurgitation is experimentally investigated by performing time-resolved particle image velocimetry in a left heart duplicator. Diastolic vortex reversal was observed in the left ventricle accompanied by an increase in viscous energy dissipation. Vortex dynamics and energy dissipation may provide useful insights on sub-optimal flow patterns in the left ventricle.     

Assessment of human left ventricle flow using statistical shape modelling and computational fluid dynamics

Blood flow patterns in the human left ventricle (LV) have shown relation to cardiac health. However, most studies in the literature are limited to a few patients and results are hard to generalize. This study aims to provide a new framework to generate more generalized insights into LV blood flow as a function of changes in anatomy and wall motion. In this framework, we studied the four-dimensional blood flow in LV via computational fluid dynamics (CFD) in conjunction with a statistical shape model (SSM), built from segmented LV shapes of 150 subjects. We validated results in an in-vitro dynamic phantom via time-resolved optical particle image velocimetry (PIV) measurements. This combination of CFD and the SSM may be useful for systematically assessing blood flow patterns in the LV as a function of varying anatomy and has the potential to provide valuable data for diagnosis of LV functionality.     

Biochemical characterization of ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP, E.C. 3.1.4.1) from rat heart left ventricle

In the present study we investigate the biochemical properties of the members of NPP family in synaptosomes prepared from rat heart left ventricles. Using p-nitrophenyl-5′-thymidine monophosphate (p-Nph-5′-TMP) as substrate for E-NPPs in rat cardiac synaptosomes, we observed an alkaline pH dependence, divalent cation dependence and the K _M value corresponded to 91.42 ± 13.97 μM and the maximal velocity (V _max ) value calculated was 63.79 ± 3.59 nmol p-nitrophenol released/min/mg of protein (mean ± SD, n = 4). Levamisole (1 mM), was ineffective as inhibitor of p-Nph-5′-TMP hydrolysis in pH 8.9 (optimum pH for the enzyme characterized). Suramin (0.25 mM) strongly reduced the hydrolysis of p-Nph-5′-TMP by about 46%. Sodium azide (10 and 20 mM) and gadolinium chloride (0.3 and 0.5 mM), E-NTPases inhibitors, had no effects on p-Nph-5′-TMP hydrolysis. RT-PCR analysis of left ventricle demonstrated the expression of NPP2 and NPP3 enzymes, but excluded the presence of NPP1 member. By quantitative real-time PCR we identified the NPP3 as the enzyme with the highest expression in rat left ventricle. The demonstration of the presence of the E-NPP family in cardiac system, suggest that these enzymes could contribute with the fine-tuning control of the nucleotide levels at the nerve terminal endings of left ventricles that are involved in several cardiac pathologies.     

Effect of turbulent models on left ventricle diastolic flow patterns simulation

Abstract

Vortex structures, as one of the most important features of cardiac flow, have a crucial impact on the left ventricle function and pathological conditions. These swirling flows are closely related to the presence of turbulence in left ventricle which is investigated in the current study. Using an extended model of the left heart, including a fluid-structure interaction (FSI) model of the mitral valve with a realistic geometry, the effect of using two numerical turbulent models, k-ε and Spalart-Allmaras (SA), on diastolic flow patterns is studied and compared with results from laminar flow model. As a result of the higher dissipation rate in turbulent models (k-ε and SA), vortices are larger and stronger in the laminar flow model. Comparing E/A ratio in the three models (Laminar, k-ε, and SA) with experimental data from healthy subjects, it is concluded that the results from k-ε model are more accurate.     

Coenzyme Q10 and key enzyme activities in papillary muscle related to left ventricle function in mitral valve disease

Coenzyme Q₁₀ (CoQ₁₀) was studied in papillary muscle from 18 patients (52–67 years, 2 females) subjected to open heart surgery due to mitral valve disease. In addition the enzyme activities of lactate dehydrogenase (LD) with its five isozymes, citrate synthase (CS) and mitochondrial CK (CK-MIT) were determined. Myocardial function was assessed by means of left ventricle (LV) angiography. CoQ₁₀ averaged 0.39 (range 0.26–0.59) g × mg^–1 dw. On an individual basis CoQ₁₀ was related to CS activity although not as closely as CK-MIT (r = 0.45, p<0.05 versus r = 0.86, p<0.001). The ratio (CoQ₁₀) × (CS activity)^–1 was calculated to represent mitochondrial quality. The level of LD₃ fraction increase was used to mark for the degree of metabolic stress in the heart. LD₃ fraction was negatively related to the quality index (r = –0.71, p<0.001). Thus, those with a low CoQ₁₀ per unit of CS activity had also a high LD₃ isozyme fraction. In a subset of 12 patients with isolated mitral regurgitation due to myxomatous valve degeneration, CoQ₁₀ and the ratio CoQ₁₀ over CS decreased with the degree of LV function impairment (r = –0.58, p<0.05 and r = –0.68, p<0.05, respectively). The quality index takes into account not only enzyme activity but also the potential for control of free oxygen radicals.     

Clinical and Molecular Implications of Osteopontin in Heart Failure

The matricellular protein osteopontin modulates cell–matrix interactions during tissue injury and healing. A complex multidomain structure of osteopontin enables it not only to bind diverse cell receptors but also to interact with various partners, including other extracellular matrix proteins, cytokines, and growth factors. Numerous studies have implicated osteopontin in the development and progression of myocardial remodeling in diverse cardiac diseases. Osteopontin influences myocardial remodeling by regulating extracellular matrix production, the activity of matrix metalloproteinases and various growth factors, inflammatory cell recruitment, myofibroblast differentiation, cardiomyocyte apoptosis, and myocardial vascularization. The exploitation of osteopontin loss- and gain-of-function approaches in rodent models provided an opportunity for assessment of the cell- and disease-specific contribution of osteopontin to myocardial remodeling. In this review, we summarize the recent knowledge on osteopontin regulation and its impact on various cardiac diseases, as well as delineate complex disease- and cell-specific roles of osteopontin in cardiac pathologies. We also discuss the current progress of therapeutics targeting osteopontin that may facilitate the development of a novel strategy for heart failure treatment.     

Tomographic PIV in a model of the left ventricle: 3D flow past biological and mechanical heart valves

Left ventricular flow is intrinsically complex, three-dimensional and unsteady. Its features are susceptible to cardiovascular pathology and treatment, in particular to surgical interventions involving the valves (mitral valve replacement). To improve our understanding of intraventricular fluid mechanics and the impact of various types of prosthetic valves thereon, we have developed a custom-designed versatile left ventricular phantom with anatomically realistic moving left ventricular membrane. A biological, a tilting disc and a bileaflet valve (in two different orientations) were mounted in the mitral position and tested under the same settings. To investigate 3D flow within the phantom, a four-view tomographic particle image velocimetry setup has been implemented. The results compare side-by-side the evolution of the 3D flow topology, vortical structures and kinetic energy in the left ventricle domain during the cardiac cycle. Except for the tilting disc valve, all tested prosthetic valves induced a crossed flow path, where the outflow crosses the inflow path, passing under the mitral valve. The biological valve shows a strong jet with a peak velocity about twice as high compared to all mechanical heart valves, which makes it easier to penetrate deeply into the cavity. Accordingly, the peak kinetic energy in the left ventricle in case of the biological valve is about four times higher than the mechanical heart valves. We conclude that the tomographic particle imaging velocimetry setup provides a useful ground truth measurement of flow features and allows a comparison of the effects of different valve types on left ventricular flow patterns.     

Experimental acute hypoxia in healthy subjects: evaluation of systolic and diastolic function of the left ventricle at rest and during exercise using echocardiography

To clarify whether or not systolic and diastolic function of the human left ventricle (LV) were decreased during acute hypoxia, at rest and with exercise, 14 healthy male volunteers [age 25.9 (SD 3.0) years, height 182.9 (SD 7.1) cm, body mass 75.9 (SD 6.9)kg] were examined using M-mode and 2D-mode echocardiography to determine the systolic LV function as well as Doppler-echocardiography for the assessment of diastolic LV function on 2 separate test days. In random order, the subjects breathed either air on 1 day (N) or a gas mixture with reduced oxygen content on the other (H; oxygen fraction in inspired gas 0.14). Measurements on either day were made at rest, several times during incremental cycle exercise in a supine position (6-min increments of 50 W, maximal load 150 W) and in 6th min of recovery. Corresponding measurements during N and H were compared statistically. Arterial O₂ tension (P _aO₂) was normal on N-day. All subjects showed a marked acute hypoxia at rest [P _aO₂, 54.5 (SD 4.6) mmHg], during exercise and recovery on H-day. The latter was associated with tachycardia compared to N-day. All echocardiographic measurements at rest were within the limits of normal values on both test days. Ejection time, end-systolic and end-diastolic left ventricular dimensions as well as the thickness of left posterior wall and of interventricular septum showed no statistically significant influence of H either at rest or during exercise. Stroke volume and cardiac output were always higher on H-day, which could be attributed to a slight reduction in end-systolic volume with unaffected end-diastolic volume as well as to increased heart rates. Among the indices of systolic LV function the fractions of thickening in the left ventricular posterior wall and interventricular septum showed no differences between H and N at rest or during exercise. However, fibre shortening, ejection fraction and mean circumferential fibre shortening were increased on H-day on all occasions. The mitral-valve-Doppler ratio, the index of diastolic LV function, was decreased with H at rest, showed a more pronounced reduction during exercise and was still lower in 6th min of recovery compared to N-day. It was concluded that with acute hypoxia of the severity applied in this study left ventricular systolic function in our healthy subjects showed a pronounced improvement and left ventricular diastolic function was reduced, both at rest and with exercise.     

Dopamine-beta-hydroxylase activity in plasma obtained from the pulmonary artery and left ventricle of man

Dopamine-β-hydroxylase activity (DBH) has been measured in plasma obtained simultaneously from the pulmonary artery and left ventricle of fourteen patients who underwent diagnostic cardiac catheterisation. In the majority of these subjects the levels of enzyme activity in the arterial and venous blood were similar, indicating that inactivation of DBH had not occurred in its passage through the pulmonary circulation. One patient with pulmonary hypertension had a large a-v difference in enzyme activity that may have been caused by altered pulmonary haemodynamics. Three of the five subjects that undertook a standardised exercise test on a bicycle ergometer showed a significant increase in plasma DBH activity. There was no correlation between the increases in DBH activity and in cardiac index and heart rate.     

Torsional motion of the left ventricle does not affect ventricular fluid dynamics of both foetal and adult hearts

Left ventricular torsion is caused by shortening and relaxation of the helical fibres in the myocardium, and is thought to be an optimal configuration for minimizing myocardial tissue strains. Characteristics of torsional motion has also been proposed to be markers for cardiac dysfunction. However, its effects on fluid and energy dynamics in the left ventricle have not been comprehensively investigated. To investigate this, we performed image-based flow simulations on five healthy adult porcine and two healthy human foetal left ventricles (representing two different length scales) at different degrees of torsional motions. In the adult porcine ventricles, cardiac features such as papillary muscles and mitral valves, and cardiac conditions such as myocardial infarctions, were also included to investigate the effect of twist. The results showed that, for all conditions investigated, ventricular torsional motion caused minimal changes to flow patterns, and consistently accounted for less than 2% of the energy losses, wall shear stresses, and ejection momentum energy. In contrast, physiological characteristics such as chamber size, stroke volume and heart rate had a much greater influence on flow patterns and energy dynamics. The results thus suggested that it might not be necessary to model the torsional motion to study the flow and energy dynamics in left ventricles.     

Complex distributions of residual stress and strain in the mouse left ventricle: experimental and theoretical models

 Most soft biological tissues, including ventricular myocardium, are not stress free when all external loads are removed. Residual stress has implications for mechanical performance of the heart, and may be an indicator of patterns of regional growth and remodeling. Cross-sectional rings of arrested ventricles opened up when a radial cut was made (initial mean opening angles were 64 ± 17°), but further circumferential cuts revealed the presence of additional residual stresses in the tissue with further opening of the rings. In normal mouse hearts, the inner half of a short-axis ring opened more than the outer half, and this change was dependent on apex–base location. At the apex the inner section vs. outer section opening angles were 226 ± 47° vs. 89 ± 28°, while at the base the same two angles were 160 ± 30° vs. 123 ± 35°. A simple theoretical cylindrical shell model with incompressible hyperelastic material properties was used to model the experimental deformations based on the cutting experiments. The model predicts different residual stress fields depending on the nature of the opening after the circumferential cut (which is done after the conventional radial cut). The observed opening angles were consistent with steep stress gradients near the endocardium compared with those predicted if the first cut was assumed to relieve all residual stresses. These results imply a more complex distribution of residual stress and strain in ventricular myocardium than previously thought. Received: 23 May 2002 / Accepted: 30 September 2002 We would like to acknowledge the surgical skills and data analysis of Zuangjie Li. This work was supported in part by National Heart, Lung, and Blood Institute Grants HL-43026 and HL-64321.     

Interaction between the septum and the left (right) ventricular free wall in order to evaluate the effects on coronary blood flow: numerical simulation

Mathematical modelling of the cardiovascular system (CVS) can help in understanding the complex interactions between both the ventricles and the septum. By describing the behaviour of the left (right) ventricular free wall, atria and septum using the variable elastance models, it is possible to reproduce their interactions. By relating the mechanical properties of both atria and both ventricles to the electrocardiogram (ECG) signal, it is possible to analyse the effects produced by different ECG delay on haemodynamic parameters. In the cardiovascular field, the incorrect interactions between septum and both ventricular free walls are based on many pathological conditions, i.e. symptomatic heart failure resulting from systolic dysfunction, ischemic dilated cardiomyopathy, and so on. The possible corrections that can be induced on the QRS complex duration in the ECG signal (i.e. cardiac resynchronisation therapy, CRT) can produce benefits improving the clinical status of the patient. The aim of this work was to evaluate, using our numerical simulator of the CVS, the effects induced on coronary blood flow (CBF) and aortic pressure using different ECG times, intra-ventricular and inter-ventricular delays. The results were obtained by reproducing the circulatory baseline and CRT conditions of seven patients described in literature. Haemodynamic simulated results are in accordance with literature data. Also the controversial results on CBF, in presence of CRT, are consistent with those described in the literature.     

Comparison of gene expression between left atria and left ventricles from non-diseased humans

We examine the reliability and accuracy of gene array technology in analyzing differences in gene expression between human non-diseased left atrium and left ventricle. We have used cDNA gene arrays and validated those data by carefully designed quantitative real-time polymerase chain reaction (PCR). We have identified pitfalls using cDNA gene array technology based on comparisons with other gene array studies and with changes reported for the levels of expression of the genes corresponding to these cDNAs. The high error rate reported here underscores the cautionary comments reported by others in this field.