Cardiovascular Circulatory System Research Articles

P-772 Assisted reproductive technology and the risk of minor congenital heart defects in the newborn

Abstract Study question Are children conceived through assisted reproductive technology (ART) at higher risk of minor congenital heart defects (CHD) compared with naturally conceived (NC) children? Summary answer Contrary to previous studies children conceived through ART had similar risk of minor CHDs compared with children conceived naturally. What is known already Congenital heart defects (CHD) may precipitate cardiac arrhythmias, lead to thromboembolic events, culminate in heart failure or even sudden cardiac demise. A systematic review and meta-analysis showed an elevated odds ratio (OR) for diagnosis of any CHD among children conceived through in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared with NC children. Other studies indicate that ART is associated with an increased arterial blood pressure and vascular dysfunction in the pulmonary and systemic arterial vasculature. This association persists throughout childhood, adolescence, and early adulthood in individuals conceived through ART; this indicates a lasting impact on the cardiovascular circulatory system. Study design, size, duration The present study is a sub-study to the Copenhagen Baby Heart Study (CBHS), a prospective population-based cohort study of > 25 000 children born in the three main maternity wards in Copenhagen, Denmark, in 2016–2018. Transthoracic echocardiography (TTE) was performed on all children within 60 days of delivery and diagnosis of CHD was reviewed by a specialist in paediatric cardiology. Information regarding parental health, pregnancy, delivery, and the newborn was collected through Danish patient registries. Participants/materials, setting, methods This study includes all children conceived by ART in the CBHS (n = 1 784), and a matched group (1:4 by maternal age at birth) of NC children (n = 7 141). Exclusion criteria were genetic or chromosomal syndromes and heart surgery. Minor CHD was defined as an atrial (ASD) or ventricular septum defects (VSD), bicuspid aortic valve, coarctation of the aorta, pulmonary stenosis, or patent ductus arteriosus. We calculated ORs using logistic regression analyses. Main results and the role of chance The mean maternal age at birth was 34.9 (standard deviation [SD] ±4.4) and 35.1 years (SD ± 4.6) and the newborn mean age at TTE was 12.1 (SD ± 9.3) and 12.2 days (SD ± 9.4) in the ART and NC population, respectively. Parental CHD was registered in 40 (2.2 %) children in the ART group and 121 (1.7 %) in the NC group. Overall, 165 (9.2%) children conceived by ART and 611 (8.6%) NC children were diagnosed with a minor CHD. The most prevalent CHDs were VSD and ASD which accounted for 38.8 % and 35.2 % in children with CHD in the ART group, respectively, and 36.8 % and 33.9 % in children with CHD in the NC group. The unadjusted OR for minor CHD was 1.09 (95% CI 0.91–1.30). Adjustments for maternal age and parental CHD did not change the OR. There were no differences in ORs when stratifying by minor CHD type. We stratified by the method of ART: ICSI and IVF and frozen embryo transfer and fresh embryo transfer, and calculated risk of minor CHD comparing the methods and with NC children. We found no difference in any ORs, crude or adjusted. Limitations, reasons for caution Children born preterm, and children with severe minor and major CHDs, were underrepresented in the cohort indicating parents of such children chose not to participate in a research project that would include another hospital visit. Residual confounding is plausible because parental CHD diagnoses were retrieved from patient registries. Wider implications of the findings The number of children conceived through ART is increasing each year and previous research have found an increased risk of CHD in children conceived through ART. Our findings indicate no increased risk of minor CHD, providing comforting and significant information for advising individuals considering or undergoing ART treatment. Trial registration number NCT02753348

The relationship between the secondary vascular system and the lymphatic vascular system in fish.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. However, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems among different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: a cardiovascular circulatory system, and a lymphatic vascular system (LVS), in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the 'fish lymphatics' are a specialised subcompartment of the cardiovascular system, called the secondary vascular system (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or completely from an embryonic LVS by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish possess more than the five vascular endothelial growth factor (VEGF) genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole-genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including phylogenetic knowledge.

Impact of hypertension on mean transvalvular gradients in aortic stenosis Lessons learned from in silico modelling

Abstract Introduction The influence of hypertension on the diagnostic assessment of aortic stenosis (AS) severity is unclear, yet clinically relevant. To clarify the effect of hypertension on transvalvular gradients, requires a better understanding of the impact that blood pressure change has on mean flow rate. Also, the effect of various degrees of AS severity, the valve geometry and intrinsic left ventricular contractile function (elastance) on this interaction, needs to be clarified. Existing clinical research on this topic is limited by not incorporating the full complement of factors that influences the directionality and magnitude of mean transvalvular gradient change for any given change in blood pressure. Purpose To use validated flow dynamics modelling grounded in fundamental physics principles to create a digital platform where various parameters can be manipulated to quantify the effects of bloodpressure change on mean transvalvular gradients in various pathological states. Methods A validated, zero-dimensional electro-hydraulic analogue computer model of the human cardiovascular circulatory system was generated. It was used to assess the impact of blood pressure changes on left ventricular pressure and transvalvular gradients at various flow rates, left ventricular elastances, a range of aortic valve areas and for different aortic valve morphologies. Results Mean transvalvular gradients are flow dependent. The impact of hypertension on mean flow rate (MFR), and hence on mean gradient (MG), is influenced by the aortic valve area as well as the underlying left ventricular elastance (Figure 1). Subsequently, the relationship between MFR and MG could be modelled (Figure 2). Generally, for a given change in systemic arterial pressure, the impact on MG will be the most marked for lower flow rate states such as is expected in more severe degrees of AS and for worse intrinsic left ventricular (LV) contractility. Furthermore, for a constant hemodynamic valve area, the hydraulic valve orifice area was found to be smaller in rheumatic AS compared to degenerative AS. This results in less susceptibility to blood pressure induced changes in mean transvalvular gradient. Similarly, the size of the aortic root was found to be inversely related to the susceptibility to induce a change in mean gradient for a change in blood pressure. Conclusion The interaction between hypertension and mean gradients in AS is complex. The current work places previous recommendations in perspective by quantifying the magnitude of the effect that a change in blood pressure has on mean gradient in various pathophysiological states. By doing so it provides more granularity into this multifaceted interaction compared to previously oversimplified deductions from clinical studies. The findings of this study creates a basic science framework based on first principles that dictates the scope of parameters that should be considered in future clinical research on the topic.Modelling 1Modelling 2

Maternal Cardiovascular Responses to Position Change in Pregnancy.

The maternal cardiovascular-circulatory system undergoes profound changes almost from the conception of a pregnancy until the postpartum period to support the maternal adaptions required for pregnancy and lactation. Maintenance of cardiovascular homeostasis requires changes in the cardiovascular autonomic responses. Here, we present a longitudinal study of the maternal cardiovascular autonomic responses to pregnancy and maternal position. Over a normal gestation, in the left lateral position there are significant changes in both time and frequency domain parameters reflecting heart rate variability. We show that cardiovascular autonomic responses to physiological stressors (standing and supine positions in late pregnancy) became significantly different with advancing gestation. In the third trimester, 60% of the subjects had an unstable heart rate response on standing, and these subjects had a significantly reduced sample entropy evident in their heart rate variability data. By 6 weeks, postpartum function returned to near the non-pregnant state, but there were consistent differences in high-frequency power when compared to nulligravid cases. Finally, we review complementary evidence, in particular from magnetic resonance imaging, that provides insights into the maternal and fetal impacts of positioning in pregnancy. This demonstrates a clear relationship between supine position and maternal hemodynamic parameters, which relates to compression of the inferior vena cava (p = 0.05). Together, these studies demonstrate new understanding of the physiology of physiological stressors related to position.

A Physiological Control for Artificial Heart Pump based on Adaptive Regulation of Heart Rate and the improved BAS Algorithm Optimization

In order to solve the problem that the traditional artificial heart pump has poor dynamic bionic performance and cannot respond to blood perfusion in real time according to the patient’s state, this paper proposes a new physiological control method based on adaptive adjustment of heart rate. Firstly, a coupled model of the cardiovascular circulatory system and artificial heart pump was established, and the correctness of the model is verified by hemodynamic simulation. Secondly, according to the model-free adaptive control theory, the artificial heart pump physiological control strategy for adaptive regulation of heart rate is designed, including pseudo partial derivative estimation algorithm and adaptive control law. Then, the parameters of the adaptive controller are optimized by the improved beetle antennae search algorithm. Finally, the auxiliary effect and dynamic performance of the adaptive control strategy are studied by numerical methods. The results show that the physiological control method based on adaptive regulation of heart rate realizes the adaptive modulation of heart rate and blood flow, which can meet the needs of blood perfusion in different states and help to promote the recovery of damaged heart.

In-silico modelling of the impact of hypertension on the mean transvalvular gradients in aortic stenosis.

The influence of hypertension on the diagnostic assessment of aortic stenosis (AS) severity is unclear, yet clinically relevant. To clarify the effect of hypertension on transvalvular gradients, requires a better understanding of the impact that blood pressure change has on mean flow rate. Also, the effect of various degrees of AS severity, the valve geometry and intrinsic left ventricular contractile function (elastance) on this interaction, needs to be clarified. The current work aims to assess this interaction and the magnitude of these effects. A validated, zero-dimensional electro-hydraulic analogue computer model of the human cardiovascular circulatory system was generated. It was used to assess the impact of blood pressure changes on left ventricular pressure and transvalvular gradients at various flow rates, left ventricular elastances, a range of aortic valve areas and for different aortic valve morphologies. The magnitude of the impact of hypertension induced changes on the mean gradient (MG) is influenced by the mean flow rate, the AS severity, the hydraulic effective valve orifice area and the left ventricular elastance. Generally, for a given change in systemic arterial pressure, the impact on MG will be the most marked for lower flow rate states such as is expected in more severe degrees of AS, for worse intrinsic left ventricular (LV) contractility, shorter ejection times and lower end diastolic LV volumes. Given the above conditions, the magnitude of the effect will be more for a larger aortic sinus diameter, and also for a typical degenerative valve morphology compared to a typical rheumatic valve morphology. The interaction between hypertension and mean gradients in AS is complex. The current work places previous recommendations in perspective by quantifying the magnitude of the effect that the changes in blood pressure has on mean gradient in various pathophysiological states. The work creates a framework for the parameters that should be considered in future clinical research on the topic.

REATIVIDADE DA AORTA TORÁCICA EM PACIENTES OBESOS SUBMETIDOS AO EXERCÍCIO AERÓBICO

ABSTRACT Introduction: Aerobic exercise can improve the function of the cardiovascular circulatory system, reducing morbidity and mortality from cardiovascular disease by stimulating the production of endogenous self-protection. Activating potassium channels in vascular smooth muscle cells can cause vasodilation and increase blood flow, lowering blood pressure. There is a sensitivity to intracellular ATP and ADP concentration among the variety of potassium channels distributed in vascular smooth muscle cells, which vary mainly during aerobic physical activity. Objective: Explore the effect of aerobic exercise on the vascular reactivity of the thoracic aorta in patients with obesity and hyperlipidemia. Methods: Randomized controlled trial in twenty male Wistar rats weighing 250g and two months old. The control group remained at rest while the experimental group performed aerobic exercise on a treadmill at increasing speed for eight weeks. The rats were dissected, and dilatators and vasoconstrictors drugs stimulated their blood vessels in a tamponade solution. Observation of vascular changes was measured under controlled tensioning. Results: The blockade of KATP channels in vascular smooth muscle caused tonic contraction of vascular smooth muscle cells and increased blood pressure. Conclusion: Long-term regular aerobic exercise may induce changes in rats’ thoracic aortic vascular function and vascular smooth muscle reactivity. Aerobic exercise can also significantly improve the activity of KATP channels. Evidence Level II; Therapeutic Studies – Investigating the results.

Cardiovascular Circulatory System and Left Carotid Model: A Fractional Approach to Disease Modeling

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, according to recent reports from the World Health Organization (WHO). This fact encourages research into the cardiovascular system (CVS) from multiple and different points of view than those given by the medical perspective, highlighting among them the computational and mathematical models that involve experiments much simpler and less expensive to be performed in comparison with in vivo or in vitro heart experiments. However, the CVS is a complex system that needs multidisciplinary knowledge to describe its dynamic models, which help to predict cardiovascular events in patients with heart failure, myocardial or valvular heart disease, so it remains an active area of research. Firstly, this paper presents a novel electrical model of the CVS that extends the classic Windkessel models to the left common carotid artery motivated by the need to have a more complete model from a medical point of view for validation purposes, as well as to describe other cardiovascular phenomena in this area, such as atherosclerosis, one of the main risk factors for CVDs. The model is validated by clinical indices and experimental data obtained from clinical trials performed on a pig. Secondly, as a first step, the goodness of a fractional-order behavior of this model is discussed to characterize different heart diseases through pressure–volume (PV) loops. Unlike other models, it allows us to modify not only the topology, parameters or number of model elements, but also the dynamic by tuning a single parameter, the characteristic differentiation order; consequently, it is expected to provide a valuable insight into this complex system and to support the development of clinical decision systems for CVDs.

Non-Invasive Risk Stratification of Hypertension: A Systematic Comparison of Machine Learning Algorithms

One of the most important physiological parameters of the cardiovascular circulatory system is Blood Pressure. Several diseases are related to long-term abnormal blood pressure, i.e., hypertension; therefore, the early detection and assessment of this condition are crucial. The identification of hypertension, and, even more the evaluation of its risk stratification, by using wearable monitoring devices are now more realistic thanks to the advancements in Internet of Things, the improvements of digital sensors that are becoming more and more miniaturized, and the development of new signal processing and machine learning algorithms. In this scenario, a suitable biomedical signal is represented by the PhotoPlethysmoGraphy (PPG) signal. It can be acquired by using a simple, cheap, and wearable device, and can be used to evaluate several aspects of the cardiovascular system, e.g., the detection of abnormal heart rate, respiration rate, blood pressure, oxygen saturation, and so on. In this paper, we take into account the Cuff-Less Blood Pressure Estimation Data Set that contains, among others, PPG signals coming from a set of subjects, as well as the Blood Pressure values of the latter that is the hypertension level. Our aim is to investigate whether or not machine learning methods applied to these PPG signals can provide better results for the non-invasive classification and evaluation of subjects’ hypertension levels. To this aim, we have availed ourselves of a wide set of machine learning algorithms, based on different learning mechanisms, and have compared their results in terms of the effectiveness of the classification obtained.

Developmental toxicity of chlorpropham induces pathological changes and vascular irregularities in zebrafish embryos

Chlorpropham is used to prevent sprouting in stored agricultural products. It functions through mitosis inhibition or microtubule assembly inhibition in target organisms including plants, protozoa, and fungi. Although the toxicity ranges of chlorpropham in different organisms are known, specific studies on the environmental contamination and the harmful effects of chlorpropham has not been elucidated. In the present study, we demonstrated that toxicity assays of chlorpropham using zebrafish embryos showed pathological morphology alteration with half the embryos undergoing embryonic death. Fluorescent dye was used in live embryos to identify whether oxidative stress and apoptosis mediated developmental malformation. Specific genes related to apoptosis, ccnd1, ccne1, and cdk6, belonging to cell cycle regulation were downregulated on exposure to sublethal concentrations of chlorpropham. Moreover, vascular morphogenesis, which contributes to the cardiovascular circulatory system, was disrupted by chlorpropham along with decreased expression of specific regulators (flt1, kdr, and vegfaa). These data suggest that environmentally preserved chlorpropham is a potential pollutant in non-target species, especially in aquatic organisms, and emphasizes the need for caution regarding the ecotoxicity of chlorpropham.

Медично-гіґієнічна оцінка впливу нітратів джерел децентралізованого водопостачання на захворюваність систем серцево-судинної та кровообігу

Aim. To analyze the levels of nitrate pollution of decentralized water supply sources in the settlements of Lviv region, and to investigate their influence on the formation of morbidity of the cardiovascular and circulation system among the adult population of the region. Materials and Methods. The study was conducted according to the results of monitoring the nitrate content (mg / dm3) in the decentralized water supply sources for the period of 2012-2018 and the morbidity of the cardiovascular and circulation system of the adult population of 20 districts of Lviv region during 2012-2016. The assessment of health hazards for the adult population of Lviv region from consumption of nitrate-contaminated drinking water was carried out in accordance with the risk assessment methodology based on the calculated hazard coefficients (HQ). The results were processed by traditional methods of variation statistics using licensed computer programs Microsoft Excel and Statistica 10.0. Results and Discussion. The laboratory survey covered 2212 (2012) - 2468 (2018) sources of decentralized water supply in Lviv region. There is a clear tendency of increase in the level of nitrate contamination of the drinking water. Excessive nitrate content was found in 18.6-21.7% of individual sources, 9.9-10.5% of public wells and 12.6-13.3% of public captures. The highest concentrations and the highest percentage of excesses were registered in Mykolaiv, Zhovkva, Zolochiv, and Pustomyty districts, and the smallest of excess nitrates was recorded in Turka, Sambir and Staro-Sambir districts. The average excess nitrate content in the most polluted areas was in the range of 3.3-8.0 MAC, which corresponds to concentrations at 165-400 mg/dm3. The highest rates of cardiovascular morbidity and circulatory system were registered in areas where the population uses mainly decentralized water sources and cases were recorded of significant excess of nitrates in drinking water. The statistical analysis found positive correlation connections between the development of ischemia (moderate, r=0.49, p<0.05), angina pectoris (average, r=0.77, p<0.05), and hypertension (severe, r=0.99, p <0.05) and nitrate content in the drinking water. The determination coefficients were 23.08%, 59.58% and 98.01%, respectively. According to the results of the regression analysis, an adequate mathematical model was constructed to predict the probable development of this pathology among the adult population of the region. An assessment of the health hazard for adults consuming drinking water contaminated with nitrates indicates a threat of increased non-infection morbidity, including that of cardiovascular and circulation system, namely an increase in the average (HQ 1-5) risk of nitrates at 1.8-5.0 MAC to high (HQ 5-10) - at their concentration of 5.9-8.0 MAC. Conclusions. The solution to the problem of reducing nitrate pollution of drinking water should be included amongthe most important issues not only in the field of environmental protection, but also the protection of public health. Improving the environment will help reduce the load on the healthcare system in terms of preventing and treating cardiovascular disease. Keywords: nitrates, drinking water, cardiovascular diseases, diseases of the circulatory system

Hypertension Assessment Using Photoplethysmography: A Risk Stratification Approach.

Hypertension is a common chronic cardiovascular disease (CVD). Early screening and diagnosis of hypertension plays a major role in its prevention and in the control of CVDs. Our study discusses the early screening of hypertension while using the morphological features of photoplethysmography (PPG). Numerous morphological features of PPG and its derivative waves were defined and extracted. Six types of feature selection methods were chosen to screen and evaluate these PPG morphological features. The optimal features were comprehensively analyzed in relation to the physiological processes of the cardiovascular circulatory system. Particularly, the intrinsic relation and physiological significance between the formation process of systolic blood pressure (SBP) and PPG morphology features were analyzed in depth. A variety of linear and nonlinear classification models were established for the comparison trials. The F1 scores for the normotension versus prehypertension, normotension and prehypertension versus hypertension, and normotension versus hypertension trials were 72.97%, 81.82%, and 92.31%, respectively. In summary, this study established a PPG characteristic analysis model and established the intrinsic relationship between SBP and PPG characteristics. Finally, the risk stratification of hypertension at different stages was examined and compared based on the optimal feature subset.

Photoplethysmography and Deep Learning: Enhancing Hypertension Risk Stratification.

Blood pressure is a basic physiological parameter in the cardiovascular circulatory system. Long-term abnormal blood pressure will lead to various cardiovascular diseases, making the early detection and assessment of hypertension profoundly significant for the prevention and treatment of cardiovascular diseases. In this paper, we investigate whether or not deep learning can provide better results for hypertension risk stratification when compared to the classical signal processing and feature extraction methods. We tested a deep learning method for the classification and evaluation of hypertension using photoplethysmography (PPG) signals based on the continuous wavelet transform (using Morse) and pretrained convolutional neural network (using GoogLeNet). We collected 121 data recordings from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) Database, each containing arterial blood pressure (ABP) and photoplethysmography (PPG) signals. The ABP signals were utilized to extract blood pressure category labels, and the PPG signals were used to train and test the model. According to the seventh report of the Joint National Committee, blood pressure levels are categorized as normotension (NT), prehypertension (PHT), and hypertension (HT). For the early diagnosis and assessment of HT, the timely detection of PHT and the accurate diagnosis of HT are significant. Therefore, three HT classification trials were set: NT vs. PHT, NT vs. HT, and (NT + PHT) vs. HT. The F-scores of these three classification trials were 80.52%, 92.55%, and 82.95%, respectively. The tested deep method achieved higher accuracy for hypertension risk stratification when compared to the classical signal processing and feature extraction method. Additionally, the method achieved comparable results to another approach that requires electrocardiogram and PPG signals.

Comparing Classical and Fractional Order Control Strategies of a Cardiovascular Circulatory System Simulator

This paper compares two strategies, namely, feedback linearization (FBL) and classical proportional-integral-derivative (PID) controller, as well as their fractional versions, for the control of a simulator of the human cardiovascular circulatory system (CVS) in the Matlab/Simulink environment. The simulator is based on a hydraulic model of the system, realizable in practice, in which muscular contraction of the left ventricle is modelled by a pump with piston (tank of variable volume depending on the position of the piston), so that a control strategy is needed to control the velocity of the piston in order to emulate the behaviour of the heart. Simulations are given to demonstrate, on the one hand, that all strategies have good tracking and hemodynamic performance and, on the other, that dysfunctions in the CVS can be emulated applying an appropriate control strategy that allows tracking the desired reference waveform. The final objective of this work is the construction of an experimental platform based on this simulator to test swimming robots of small dimensions that allows to emulate the conditions in which these robots would navigate in the human circulatory system.

IMPACT OF COMPETITIVE FLOW ON HEMODYNAMICS OF LIMA-LAD GRAFTING WITH DIFFERENT STENOSIS: A NUMERICAL STUDY

Background and Aims: Competitive flow exists in the native coronary artery when using artery graft in the coronary artery bypass graft (CABG), and it is a major factor affecting the long-term patency of the arterial grafts. The purpose of this study is to investigate the effects of the competitive flow on hemodynamic characteristics of left internal mammary artery (LIMA). Materials and methods: Seven three-dimensional (3D) LIMA-left anterior decending (LAD) grafting models with different diameter stenoses at the trunk of LAD were reconstructed, including 25%, 40%, 50%, 60%, 75%, 90% and 100%. The boundary conditions of these models were provided by the same lumped parameter model (LPM; 0D sub-model) of cardiovascular circulatory system, which is based on 0D/3D coupling method. Results: The simulation results show that competitive flow decreases when the stenosis rate increases and backflow exists in LIMA during systole when the degree of stenosis is below 50%; the wall shear stress (WSS) of the graft increases from 0.85[Formula: see text]Pa to 1.79[Formula: see text]Pa with the increase of the native coronary stenosis degree, while the oscillatory shear index (OSI) decreases from 0.1557 to 0.00213. Conclusions: Competitive flow may produce adverse hemodynamic effects on artery graft, especially when the stenosis degree is below 50%, competitive flow will significantly lead the long-term patency of the artery graft worse because of the backflow, low WSS and high OSI, and the effect of OSI is more obvious than WSS.

Nonlinear Adaptive Control of a Piston Pump Mock Ventricle

High-performance control system for a piston pump mock ventricle is developed in this research to accurately reproduce the native ventricle's pumping dynamics and to secure the physiological feasibility of the cardiovascular circulatory simulator (CCS). The challenges are that a piston pump mock ventricle has inherent parameter uncertainties of check valve resistances, high bandwidth pressure dynamics, and hard nonlinearity due to check valves. To overcome these difficulties, a nonlinear adaptive control scheme is presented in this paper. A hardware CCS is constructed based on the electrical-analog reference model of the cardiovascular circulatory system and the mathematical model of the hardware was derived using fluidic element modeling and the parameter identification experiments. The adaptive controller was designed based on the derived model. Experimental results show that the adaptive control achieved outstanding control performance in spite of the parameter uncertainties and yielded a good match with the reference model behavior. As a result, high quality elastance curve over the whole cardiac cycle was made possible at the level that has never been achieved.

Endothelial cell metabolism in normal and diseased vasculature.

Higher organisms rely on a closed cardiovascular circulatory system with blood vessels supplying vital nutrients and oxygen to distant tissues. Not surprisingly, vascular pathologies rank among the most life-threatening diseases. At the crux of most of these vascular pathologies are (dysfunctional) endothelial cells (ECs), the cells lining the blood vessel lumen. ECs display the remarkable capability to switch rapidly from a quiescent state to a highly migratory and proliferative state during vessel sprouting. This angiogenic switch has long been considered to be dictated by angiogenic growth factors (eg, vascular endothelial growth factor) and other signals (eg, Notch) alone, but recent findings show that it is also driven by a metabolic switch in ECs. Furthermore, these changes in metabolism may even override signals inducing vessel sprouting. Here, we review how EC metabolism differs between the normal and dysfunctional/diseased vasculature and how it relates to or affects the metabolism of other cell types contributing to the pathology. We focus on the biology of ECs in tumor blood vessel and diabetic ECs in atherosclerosis as examples of the role of endothelial metabolism in key pathological processes. Finally, current as well as unexplored EC metabolism-centric therapeutic avenues are discussed.

Model-referenced cardiovascular circulatory simulator: construction and control.

Physiological feasibility is the most important requirement for cardiovascular circulatory simulators (CCSs). However, previous simulators have been validated by a comparison with specific human data sets, which are valid only for very limited conditions, and so it is difficult to validate the fidelity of a CCS for various body conditions. To overcome this critical limitation, we propose a model-referenced CCS that reproduces the behavior of an electrical-analog model of the cardiovascular circulatory system, for which physiological fidelity is well established over a wide range. In this study, the electrical-analog reference model was realized in the hardware simulator using fluidic element modeling and by the feedback control of a mock ventricle. The proposed simulator showed a good match with the reference model behavior, and its physiological validity was thereby verified. The proposed simulator is able to show responsiveness to various body conditions as well. To the best of the author's knowledge, this is the first report of an in vitro CCS verified to be consistent with reference model behavior.

Control system design for the mock ventricle with aortic and mitral valve resistance uncertainty

Reproducing the native left ventricle’s contractile behavior is the key ingredient for the mock cardiovascular circulatory system. It can be achieved by controlling either mock ventricle’s pressure or volume so that it could follow the reference signal calculated by the Elastance waveform. However, due to inherent uncertainties of the parameter values of the mock ventricle, such as check valve resistance, it is difficult to achieve high quality control performance. In this paper, we present an adaptive control scheme to overcome this parameter value uncertainty and to achieve high quality control performance. To the best knowledge of the author, it is the first report that reproduces the mock ventricle pumping dynamics precisely considering the resistance of the aortic/mitral check valves and overcoming the uncertainty of them. In the paper, along with the detailed design of the controller, rigorous proof of the stability and the convergence is presented as well. Computer simulation was performed using an electrical-analog cardiovascular circulatory system model and a piston pump mock ventricle model. Results confirmed that adaptive control achieved almost perfect tracking performance in spite of large parameter uncertainty and high bandwidth dynamic characteristics of the mock ventricle. Performance comparison verified the superiority of the adaptive controller over PID controllers.

Visualization and Development of Cerebral Circulation Simulation taking account of Cardiovascular Circulatory System

Visualization and Development of Cerebral Circulation Simulation taking account of Cardiovascular Circulatory System