Impact of Respiratory Fluctuation on Hemodynamics in Human Cardiovascular System: A 0-1D Multiscale Model

To explore hemodynamic interaction between the human respiratory system (RS) and cardiovascular system (CVS), here we propose an integrated computational model to predict the CVS hemodynamics with consideration of the respiratory fluctuation (RF). A submodule of the intrathoracic pressure (ITP) adjustment is developed and incorporated in a 0-1D multiscale hemodynamic model of the CVS specified for infant, adolescent, and adult individuals. The model is verified to enable reasonable estimation of the blood pressure waveforms accounting for the RF-induced pressure fluctuations in comparison with clinical data. The results show that the negative ITP caused by respiration increases the blood flow rates in superior and inferior vena cavae; the deep breathing improves the venous return in adolescents but has less influence on infants. It is found that a marked reduction in ITP under pathological conditions can excessively increase the flow rates in cavae independent of the individual ages, which may cause the hemodynamic instability and hence increase the risk of heart failure. Our results indicate that the present 0-1D multiscale CVS model incorporated with the RF effect is capable of providing a useful and effective tool to explore the physiological and pathological mechanisms in association with cardiopulmonary interactions and their clinical applications.

Several Theoretical and Applied Problems of Human Extreme Physiology: Mathematical Modeling

Human cardiovascular system (CVS) and hemodynamics are critically sensitive to essential alterations of mechanical inertial forces in directions of head-legs (+Gz) or legs-head (-Gz). Typically, such alterations appear during pilotage maneuvers of modern high maneuverable airspace vehicles (HMAV).The vulnerability of pilots or passengers of HMAV to these altering forces depends on their three main characteristics: amplitude, dynamics, and duration. Special protections, proposed to minimize this vulnerability, should be improved in parallel with the increasing of these hazardous characteristics of HMAVs. Empiric testing of novel protection methods and tools is both expensive and hazardous. Therefore computer simulations are encouraged. Autonomic software (AS) for simulating and theoretical investigating of the main dynamic responses of human CVS to altering Gz is developed. AS is based on a system of quantitative mathematical models (QMM) consisting of about 1300 differential and algebraic equations. QMM describes the dynamics of both CVS (the cardiac pump function, baroreceptor control of parameters of cardiovascular net presented by means of lumped parameter vascular compartments) and non-biological variables (inertial forces, and used protections). The main function of AS is to provide physiologist-researcher by visualizations of calculated additional data concerning characteristics of both external and internal environments under high sustained accelerations and short-time microgravity. Additionally, AS can be useful as an educational tool able to show both researchers and young pilots the main hemodynamic effects caused by accelerations and acute weightlessness with and without use of different protection tools and technics. In this case, AS does help users to optimize training process aimed to ensure optimal-like human tolerance to the altered physical environment. Main physiological events appearing under different scenarios of accelerations and microgravity have been tested.

Application of an automated complex resistance and phase difference measuring method for rheographic studies of human cardiovascular system

The structure of an automated system for measuring the complex resistance of the human body and the phase difference is proposed. It is used in the rheographic method for diagnosing human cardiovascular system diseases using a multilevel microcontroller structure. The metrological analysis of the automated system made it possible to achieve an increase in the measurement accuracy both by reducing the methodological and instrumental components of measurement errors. The relative basic measurement error does not exceed ± 0.5%.

The Dynamics of Coupled Oscillators

<p>The subject is introduced by considering the treatment of oscillators in Mathematics from the simple Poincar´e oscillator, a single variable dynamical process defined on a circle, to the oscillatory dynamics of systems of differential equations. Some models of real oscillator systems are considered. Noise processes are included in the dynamics of the system. Coupling between oscillators is investigated both in terms of analytical systems and as coupled oscillator models. It is seen that driven oscillators can be used as a model of 2 coupled oscillators in 2 and 3 dimensions due to the dependence of the dynamics on the phase difference of the oscillators. This means that the dynamics are easily able to be modelled by a 1D or 2D map. The analysis of N coupled oscillator systems is also described. The human cardiovascular system is studied as an example of a coupled oscillator system. The heart oscillator system is described by a system of delay differential equations and the dynamics characterised. The mechanics of the coupling with the respiration is described. In particular the model of the heart oscillator includes the baroreceptor reflex with time delay whereby the aortic fluid pressure influences the heart rate and the peripheral resistance. Respiration is modelled as forcing the heart oscillator system. Locking zones caused by respiratory sinus arrhythmia (RSA), the synchronisation of the heart with respiration, are found by plotting the rotation number against respiration frequency. These are seen to be relatively narrow for typical physiological parameters and only occur for low ratios of heart rate to respiration frequency. Plots of the diastolic pressure and heart interval in terms of respiration phase parameterised by respiration frequency illustrate the dynamics of synchronisation in the human cardiovascular system.</p>

The Dynamics of Coupled Oscillators

<p>The subject is introduced by considering the treatment of oscillators in Mathematics from the simple Poincar´e oscillator, a single variable dynamical process defined on a circle, to the oscillatory dynamics of systems of differential equations. Some models of real oscillator systems are considered. Noise processes are included in the dynamics of the system. Coupling between oscillators is investigated both in terms of analytical systems and as coupled oscillator models. It is seen that driven oscillators can be used as a model of 2 coupled oscillators in 2 and 3 dimensions due to the dependence of the dynamics on the phase difference of the oscillators. This means that the dynamics are easily able to be modelled by a 1D or 2D map. The analysis of N coupled oscillator systems is also described. The human cardiovascular system is studied as an example of a coupled oscillator system. The heart oscillator system is described by a system of delay differential equations and the dynamics characterised. The mechanics of the coupling with the respiration is described. In particular the model of the heart oscillator includes the baroreceptor reflex with time delay whereby the aortic fluid pressure influences the heart rate and the peripheral resistance. Respiration is modelled as forcing the heart oscillator system. Locking zones caused by respiratory sinus arrhythmia (RSA), the synchronisation of the heart with respiration, are found by plotting the rotation number against respiration frequency. These are seen to be relatively narrow for typical physiological parameters and only occur for low ratios of heart rate to respiration frequency. Plots of the diastolic pressure and heart interval in terms of respiration phase parameterised by respiration frequency illustrate the dynamics of synchronisation in the human cardiovascular system.</p>

Hybrid modeling of the human cardiovascular system using NeuralFMUs

Hybrid modeling, the combination of first principle and machine learning models, is an emerging research field that gathers more and more attention. Even if hybrid models produce formidable results for academic examples, there are still different technical challenges that hinder the use of hybrid modeling in real-world applications. By presenting NeuralFMUs, the fusion of a Functional Mock-up Unit (FMU), a numerical ODE solver and an artifical neural network, we are paving the way for the use of a variety of first principle models from different modeling tools as parts of hybrid models. This contribution handles the hybrid modeling of a complex, real-world example: Starting with a simplified 1D-fluid model of the human cardiovascular system (arterial side), the aim is to learn neglected physical effects like arterial elasticity from data. We will show that the hybrid modeling process is more comfortable, needs less system knowledge and is therefore less error-prone compared to modeling solely based on first principle. Further, the resulting hybrid model has improved in computation performance, compared to a pure first principle white-box model, while still fulfilling the requirements regarding accuracy of the considered hemodynamic quantities. The use of the presented techniques is explained in a general manner and the considered use-case can serve as example for other modeling and simulation applications in and beyond the medical domain.

Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration

The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling rely on animal models and a few clinical studies, which significantly bottleneck the understanding of Notch signaling-associated human cardiovascular development and disease. Recent advances in the bioengineering systems and human pluripotent stem cell-derived cardiovascular cells pave the way to decipher the role of Notch signaling in cardiovascular-related cells (endothelial cells, cardiomyocytes, smooth muscle cells, fibroblasts, and immune cells), and intercellular crosstalk in the physiological, pathological, and regenerative context of the complex human cardiovascular system. In this review, we first summarize the significant roles of Notch signaling in individual cardiac cell types. We then cover the bioengineering systems of microfluidics, hydrogel, spheroid, and 3D bioprinting, which are currently being used for modeling and studying Notch signaling in the cardiovascular system. At last, we provide insights into ancillary supports of bioengineering systems, varied types of cardiovascular cells, and advanced characterization approaches in further refining Notch signaling in cardiovascular development, disease, and regeneration.