Structure-based finite strain modelling of the human left ventricle in diastole

Finite strain analyses of the left ventricle provide important information on heart function and have the potential to provide insights into the biomechanics of myocardial contractility in health and disease. Systolic dysfunction is the most common cause of heart failure; however, abnormalities of diastolic function also contribute to heart failure, and are associated with conditions including left ventricular hypertrophy and diabetes. The clinical significance of diastolic abnormalities is less well understood than systolic dysfunction, and specific treatments are presently lacking. To obtain qualitative and quantitative information on heart function in diastole, we develop a three-dimensional computational model of the human left ventricle that is derived from noninvasive imaging data. This anatomically realistic model has a rule-based fibre structure and a structure-based constitutive model. We investigate the sensitivity of this comprehensive model to small changes in the constitutive parameters and to changes in the fibre distribution. We make extensive comparisons between this model and similar models that employ different constitutive models, and we demonstrate qualitative and quantitative differences in stress and strain distributions for the different constitutive models. We also provide an initial validation of our model through comparisons to experimental data on stress and strain distributions in the left ventricle

Evidence that conflict regarding size of haemodynamic response to interventricular delay optimization of cardiac resynchronization therapy may arise from differences in how atrioventricular delay is kept constant.

Aims: Whether adjusting interventricular (VV) delay changes haemodynamic efficacy of cardiac resynchronization therapy (CRT) is controversial, with conflicting results. This study addresses whether the convention for keeping atrioventricular (AV) delay constant during VV optimization might explain these conflicts. / Method and results: Twenty-two patients in sinus rhythm with existing CRT underwent VV optimization using non-invasive systolic blood pressure. Interventricular optimization was performed with four methods for keeping the AV delay constant: (i) atrium and left ventricle delay kept constant, (ii) atrium and right ventricle delay kept constant, (iii) time to the first-activated ventricle kept constant, and (iv) time to the second-activated ventricle kept constant. In 11 patients this was performed with AV delay of 120 ms, and in 11 at AV optimum. At AV 120 ms, time to the first ventricular lead (left or right) was the overwhelming determinant of haemodynamics (13.75 mmHg at ±80 ms, P < 0.001) with no significant effect of time to second lead (0.47 mmHg, P = 0.50), P < 0.001 for difference. At AV optimum, time to first ventricular lead again had a larger effect (5.03 mmHg, P < 0.001) than time to second (2.92 mmHg, P = 0.001), P = 0.02 for difference. / Conclusion: Time to first ventricular activation is the overwhelming determinant of circulatory function, regardless of whether this is the left or right ventricular lead. If this is kept constant, the effect of changing time to the second ventricle is small or nil, and is not beneficial. In practice, it may be advisable to leave VV delay at zero. Specifying how AV delay is kept fixed might make future VV delay research more enlightening

Altered Oxygen Utilisation in Rat Left Ventricle and Soleus after 14 Days, but Not 2 Days, of Environmental Hypoxia.

The effects of environmental hypoxia on cardiac and skeletal muscle metabolism are dependent on the duration and severity of hypoxic exposure, though factors which dictate the nature of the metabolic response to hypoxia are poorly understood. We therefore set out to investigate the time-dependence of metabolic acclimatisation to hypoxia in rat cardiac and skeletal muscle. Rats were housed under normoxic conditions, or exposed to short-term (2 d) or sustained (14 d) hypoxia (10% O2), after which samples were obtained from the left ventricle of the heart and the soleus for assessment of metabolic regulation and mitochondrial function. Mass-corrected maximal oxidative phosphorylation was 20% lower in the left ventricle following sustained but not short-term hypoxia, though no change was observed in the soleus. After sustained hypoxia, the ratio of octanoyl carnitine- to pyruvate- supported respiration was 11% and 12% lower in the left ventricle and soleus, respectively, whilst hexokinase activity increased by 33% and 2.1-fold in these tissues. mRNA levels of PPARα targets fell after sustained hypoxia in both tissues, but those of PPARα remained unchanged. Despite decreased Ucp3 expression after short-term hypoxia, UCP3 protein levels and mitochondrial coupling remained unchanged. Protein carbonylation was 40% higher after short-term but not sustained hypoxic exposure in the left ventricle, but was unchanged in the soleus at both timepoints. Our findings therefore demonstrate that 14 days, but not 2 days, of hypoxia induces a loss of oxidative capacity in the left ventricle but not the soleus, and a substrate switch away from fatty acid oxidation in both tissues

Three-dimensional structure of the flow inside the left ventricle of the human heart

The laboratory models of the human heart left ventricle developed in the last decades gave a valuable contribution to the comprehension of the role of the fluid dynamics in the cardiac function and to support the interpretation of the data obtained in vivo. Nevertheless, some questions are still open and new ones stem from the continuous improvements in the diagnostic imaging techniques. Many of these unresolved issues are related to the three-dimensional structure of the left-ventricular flow during the cardiac cycle. In this paper we investigated in detail this aspect using a laboratory model. The ventricle was simulated by a flexible sack varying its volume in time according to a physiologically shaped law. Velocities measured during several cycles on series of parallel planes, taken from two orthogonal points of view, were combined together in order to reconstruct the phase averaged, three-dimensional velocity field. During the diastole, three main steps are recognized in the evolution of the vortical structures: i) straight propagation in the direction of the long axis of a vortex-ring originated from the mitral orifice; ii) asymmetric development of the vortex-ring on an inclined plane; iii) single vortex formation. The analysis of three-dimensional data gives the experimental evidence of the reorganization of the flow in a single vortex persisting until the end of the diastole. This flow pattern seems to optimize the cardiac function since it directs velocity towards the aortic valve just before the systole and minimizes the fraction of blood residing within the ventricle for more cycles

A parallel interaction potential approach coupled with the immersed boundary method for fully resolved simulations of deformable interfaces and membranes

In this paper we show and discuss the use of a versatile interaction potential approach coupled with an immersed boundary method to simulate a variety of flows involving deformable bodies. In particular, we focus on two kinds of problems, namely (i) deformation of liquid-liquid interfaces and (ii) flow in the left ventricle of the heart with either a mechanical or a natural valve. Both examples have in common the two-way interaction of the flow with a deformable interface or a membrane. The interaction potential approach (de Tullio & Pascazio, Jou. Comp. Phys., 2016; Tanaka, Wada and Nakamura, Computational Biomechanics, 2016) with minor modifications can be used to capture the deformation dynamics in both classes of problems. We show that the approach can be used to replicate the deformation dynamics of liquid-liquid interfaces through the use of ad-hoc elastic constants. The results from our simulations agree very well with previous studies on the deformation of drops in standard flow configurations such as deforming drop in a shear flow or a cross flow. We show that the same potential approach can also be used to study the flow in the left ventricle of the heart. The flow imposed into the ventricle interacts dynamically with the mitral valve (mechanical or natural) and the ventricle which are simulated using the same model. Results from these simulations are compared with ad- hoc in-house experimental measurements. Finally, a parallelisation scheme is presented, as parallelisation is unavoidable when studying large scale problems involving several thousands of simultaneously deforming bodies on hundreds of distributed memory computing processors

Cardiovascular function and ballistocardiogram: a relationship interpreted via mathematical modeling

Objective: to develop quantitative methods for the clinical interpretation of the ballistocardiogram (BCG). Methods: a closed-loop mathematical model of the cardiovascular system is proposed to theoretically simulate the mechanisms generating the BCG signal, which is then compared with the signal acquired via accelerometry on a suspended bed. Results: simulated arterial pressure waveforms and ventricular functions are in good qualitative and quantitative agreement with those reported in the clinical literature. Simulated BCG signals exhibit the typical I, J, K, L, M and N peaks and show good qualitative and quantitative agreement with experimental measurements. Simulated BCG signals associated with reduced contractility and increased stiffness of the left ventricle exhibit different changes that are characteristic of the specific pathological condition. Conclusion: the proposed closed-loop model captures the predominant features of BCG signals and can predict pathological changes on the basis of fundamental mechanisms in cardiovascular physiology. Significance: this work provides a quantitative framework for the clinical interpretation of BCG signals and the optimization of BCG sensing devices. The present study considers an average human body and can potentially be extended to include variability among individuals