Gaps in the wall of a perivascular space act as valves to produce a directed flow of cerebrospinal fluid: a hoop-stress model.

The flow of cerebrospinal fluid (CSF) along perivascular spaces (PVSs) is an important part of the brain's system for clearing metabolic waste. Astrocyte endfeet bound the PVSs of penetrating arteries, separating them from brain extracellular space. Gaps between astrocyte endfeet might provide a low-resistance pathway for fluid transport across the wall. Recent studies suggest that the astrocyte endfeet function as valves that rectify the CSF flow, producing the net flow observed in pial PVSs by changing the size of the gaps in response to pressure changes. In this study, we quantify this rectification based on three features of the PVSs: the quasi-circular geometry, the deformable endfoot wall, and the pressure oscillation inside. We provide an analytical model, based on the thin-shell hoop-stress approximation, and predict a pumping efficiency of about 0.4, which would contribute significantly to the observed flow. When we add the flow resistance of the extracellular space (ECS) to the model, we find an increased net flow during sleep, due to the known increase in ECS porosity (decreased flow resistance) compared to that in the awake state. We corroborate our analytical model with three-dimensional fluid-solid interaction simulations.

Novel theory and potential applications of central diastolic pressure decay time constant.

Central aortic diastolic pressure decay time constant ( τ ) is according to the two-element Windkessel model equal to the product of total peripheral resistance ( R ) times total arterial compliance ( C ). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant τ with the product T MBP cPP , given by heart period ( T ) times the ratio of mean blood pressure (MBP) to central pulse pressure ( cPP ). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be τ = k ' T MBP cPP , with k ' = 0.7 (R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference τ values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient k ' is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between τ and central blood pressure features. In addition, it may allow for the evaluation of τ without the need for acquiring the entire central blood pressure wave, especially when an approximation of the cPP is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.

Reactive oxygen species augment contractile responses of saphenous artery in 10-15-day-old but not adult rats: Substantial role of NADPH oxidases.

Reactive oxygen species (ROS) produced by NADPH oxidases (NOX, a key source of ROS in vascular cells) are involved in the regulation of vascular tone, but this has been explored mainly for adult organisms. Importantly, the mechanisms of vascular tone regulation differ significantly in early postnatal ontogenesis and adulthood, while the vasomotor role of ROS in immature systemic arteries is poorly understood. We tested the hypothesis that the functional contribution of NADPH oxidase-derived ROS to the regulation of peripheral arterial tone is higher in the early postnatal period than in adulthood. We studied saphenous arteries from 10- to 15-day-old ("young") and 3- to 4-month-old ("adult") male rats using lucigenin-enhanced chemiluminescence, quantitative PCR, Western blotting, and isometric myography. We demonstrated that both basal and NADPH-stimulated superoxide anion radical (O2•-) production was significantly higher in the arteries from young in comparison to adult rats. Importantly, pan-inhibitor of NADPH oxidase VAS2870 (10 µM) reduced NADPH-induced O2•- production in arteries of young rats. Saphenous arteries of both young and adult rats demonstrated high levels of Nox2 and Nox4 mRNAs, while Nox1 and Nox3 mRNAs were not detected. The protein contents of NOX2 and NOX4 were significantly higher in arterial tissue of young compared to adult animals. Moreover, VAS2870 (10 µM) had no effect on methoxamine-induced contractile responses of adult arteries but decreased them significantly in young arteries; such effect of VAS2870 persisted after removal of the endothelium. Finally, NOX2 inhibitor GSK2795039 (10 µM), but not NOX1/4 inhibitor GKT137831 (10 µM) weakened methoxamine-induced contractile responses of arteries from young rats. Thus, ROS produced by NOX2 have a pronounced contractile influence in saphenous artery smooth muscle cells of young, but not adult rats, which is associated with the increased vascular content of NOX2 protein at this age.

Arterial Pulse Wave Velocity Signal Reconstruction Using Low Sampling Rates.

Pulse Wave Velocity (PWV) analysis is valuable for assessing arterial stiffness and cardiovascular health and potentially for estimating blood pressure cufflessly. However, conventional PWV analysis from two transducers spaced closely poses challenges in data management, battery life, and developing the device for continuous real-time applications together along an artery, which typically need data to be recorded at high sampling rates. Specifically, although a pulse signal consists of low-frequency components when used for applications such as determining heart rate, the pulse transit time for transducers near each other along an artery takes place in the millisecond range, typically needing a high sampling rate. To overcome this issue, in this study, we present a novel approach that leverages the Nyquist-Shannon sampling theorem and reconstruction techniques for signals produced by bioimpedance transducers closely spaced along a radial artery. Specifically, we recorded bioimpedance artery pulse signals at a low sampling rate, reducing the data size and subsequently algorithmically reconstructing these signals at a higher sampling rate. We were able to retain vital transit time information and achieved enhanced precision that is comparable to the traditional high-rate sampling method. Our research demonstrates the viability of the algorithmic method for enabling PWV analysis from low-sampling-rate data, overcoming the constraints of conventional approaches. This technique has the potential to contribute to the development of cardiovascular health monitoring and diagnosis using closely spaced wearable devices for real-time and low-resource PWV assessment, enhancing patient care and cardiovascular disease management.

Tube law parametrization using in vitro data for one-dimensional blood flow in arteries and veins: TUBE LAW PARAMETRIZATION IN ARTERIES AND VEINS.

The deformability of blood vessels in one-dimensional blood flow models is typically described through a pressure-area relation, known as the tube law. The most used tube laws take into account the elastic and viscous components of the tension of the vessel wall. Accurately parametrizing the tube laws is vital for replicating pressure and flow wave propagation phenomena. Here, we present a novel mathematical-property-preserving approach for the estimation of the parameters of the elastic and viscoelastic tube laws. Our goal was to estimate the parameters by using ovine and human in vitro data, while constraining them to meet prescribed mathematical properties. Results show that both elastic and viscoelastic tube laws accurately describe experimental pressure-area data concerning both quantitative and qualitative aspects. Additionally, the viscoelastic tube law can provide a qualitative explanation for the observed hysteresis cycles. The two models were evaluated using two approaches: (i) allowing all parameters to freely vary within their respective ranges and (ii) fixing some of the parameters. The former approach was found to be the most suitable for reproducing pressure-area curves.

Biological structural study of emerging shaped nanoparticles for the blood flow in diverging tapered stenosed arteries to see their application in drug delivery.

The magnetic force effects and differently shaped nano-particles in diverging tapering arteries having stenoses are being studied in current research via blood flow model. There hasn't been any research done on using metallic nanoparticles of different shapes with water as the base fluid. A radially symmetric but axially non-symmetric stenosis is used to depict the blood flow. Another significant aspect of our research is the study of symmetrical distribution of wall shearing stresses in connection with resistive impedance, as well as the rise of these quantities with the progression of stenosis. Shaping nanoparticles in accordance with the understanding of blood flow in arteries offers numerous possibilities for improving drug delivery, targeted therapies, and diagnostic imaging in the context of cardiovascular and other vascular-related diseases. Exact solutions for different flow quantities namely velocity, temperature, resistance impedance, boundary shear stress, and shearing stress at the stenosis throat, have been assessed. For various parameters of relevance for Cu-water, the graphical results of several types of tapered arteries (i.e. diverging tapering) have been explored.

Investigating hybrid nanoparticles for drug delivery in multi-stenosed catheterized arteries under magnetic field effects.

This groundbreaking study pioneers the exploration of the therapeutic implications of a constant magnetic field simultaneously with hybrid nanoparticles on blood flow within a tapered artery, characterized by multiple stenosis along its exterior walls and a central thrombus, employing three-dimensional bio-fluid simulations. In addition, a magnetized catheter is inserted into the thrombus to increase the therapeutic potential of this novel method. The flow condition under consideration has applications in targeted medication distribution, improved medical device design, and improved diagnostics, as well as in advancing healthcare and biomedical engineering. Our investigation primarily aims to optimize blood flow efficiency, encompassing key parameters like pressure, velocity, and heat fluctuations influenced by diverse geometric constraints within the stenotic artery. Precise solutions are obtained through the finite element method (FEM) coupled with advanced bio-fluid dynamics (BFD) software. Hybrid nanoparticles and magnetic fields impacted pressure and velocity, notably reducing pressure within the stenosis. Convective heat flux remained uniform, while temperature profiles showed consistent inlet rise and gradual decline with transient variations. This approach promotes fluid flow, and convection within stenosed arteries, enhances heat transport, evacuates heat from stenotic regions, and improves heat dispersion to surrounding tissues. These findings hold promise for targeted therapies, benefiting patients with vascular disorders, and advancing our understanding of complex bio-fluid dynamics.

Anatomical and physiological adaptation of the scrotal artery with muscular reinforcement in the middle layer and connective reinforcement of the adventitia.

The histology of blood vessels shows they are structured in three layers or tunics: tunica intima, which includes the internal limiting lamina with high elastin content; tunica media of smooth muscles fibers of circular disposition, which includes the external limiting lamina; and tunica adventitia of connective tissue. The vascular system is essential in regulating body temperature, especially in the scrotum and testis. This study aimed to analyze the histology of the scrotal arteries and their possible relationship to testicular temperature homeostasis. This study used scrotal samples from human adults, anonymized and obtained from the University of Chile's teaching bank. The control group corresponds to an arteriole of muscle tissue. The results show that the middle layer of the scrotal artery is made up of smooth muscle fibers distributed in two layers: a longitudinal inner sublayer and a circular outer sublayer, different from the findings in muscle tissue arteries, with a single, circularly arranged muscle layer. This arrangement could be related to testicular temperature homeostasis by reducing the temperature of the testis and seminiferous tubules. The results described in this work suggest that these anatomical adaptations may be very significant in the face of the constant increase in global temperature. Further and better research is required to understand the mechanisms of thermoregulation in human reproduction and the histological particularities of the tissues that form the scrotum. RESEARCH HIGHLIGHTS: The human scrotal artery has a histological composition adapted for regulation of testicular temperature. The muscular double middle layer of the scrotal artery retains intravascular temperature.

Integrated particle image velocimetry and fluid-structure interaction analysis for patient-specific abdominal aortic aneurysm studies.

BACKGROUND: Understanding the hemodynamics of an abdominal aortic aneurysm (AAA) is crucial for risk assessment and treatment planning. This study introduces a low-cost, patient-specific in vitro AAA model to investigate hemodynamics using particle image velocimetry (PIV) and flow-simulating circuit, validated through fluid-structure interaction (FSI) simulations. METHODS: In this study, 3D printing was employed to manufacture a flexible patient-specific AAA phantom using a lost-core casting technique. A pulsatile flow circuit was constructed using off-the-shelf components. A particle image velocimetry (PIV) setup was built using an affordable laser source and global shutter camera, and finally, the flow field inside the AAA was analyzed using open-source software. Fluid-structure interaction (FSI) simulations were performed to enhance our understanding of the flow field, and the results were validated by PIV analysis. Both steady-state and transient flow conditions were investigated. RESULTS: Our experimental setup replicated physiological conditions, analyzing arterial wall deformations and flow characteristics within the aneurysm. Under constant flow, peak wall deformations and flow velocities showed deviations within - 12% to + 27% and - 7% to + 5%, respectively, compared to FSI simulations. Pulsatile flow conditions further demonstrated a strong correlation (Pearson coefficient 0.85) in flow velocities and vectors throughout the cardiac cycle. Transient phenomena, particularly the formation and progression of vortex structures during systole, were consistently depicted between experimental and numerical models. CONCLUSIONS: By bridging high-fidelity experimental observations with comprehensive computational analyses, this study underscores the potential of integrated methodologies in enhancing our understanding of AAA pathophysiology. The convergence of realistic AAA phantoms, precise PIV measurements at affordable cost point, and validated FSI models heralds a new paradigm in vascular research, with significant implications for personalized medicine and bioengineering innovations.

Numerical simulation of effect of hybrid nanofluid on heat transfer and flow of the Newtonian pulsatile blood through 3D occluded artery: Silver and gold nanoparticles.

The study of blood flow in obstructed arteries is a significant focus in computational fluid dynamics, particularly in the field of biomedicine. The primary objective of this research is to investigate the impact of pulsating blood velocity on heat transfer within biological systems, with a specific focus on blood flow in obstructed arteries. To achieve this goal, a comprehensive 3D model representing a straight, constricted blood vessel has been developed. This model incorporates periodic, unsteady, Newtonian blood flow along with the presence of gold and silver nanoparticles. Leveraging the Finite Element Method (FEM), the Navier-Stokes and energy equations have been rigorously solved. Through the investigation, it is aim to shed light on how alterations in the pulsation rate and the volume fraction of nanoparticles influence both temperature distribution and velocity profiles within the system. The present study findings unequivocally highlight that the behavior of pulsatile nanofluid flow significantly impacts the velocity field and heat transfer performance. However, it is imperative to note that the extent of this influence varies depending on the specific volume fractions involved. Specifically, higher volume fractions of nanofluids correlate with elevated velocities at the center of the vessel and decreased velocities near the vessel walls. This pattern also extends to the temperature distribution and heat flux within the vessel, further underscoring the paramount importance of pulsatile flow dynamics in biomedicine and computational fluid dynamics research. Besides, results revealed that the presence of occlusion significantly affects the heat transfer and fluid flow.

In vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice.

Altered vasoactivity is a major characteristic of cardiovascular and oncological diseases, and many therapies are therefore targeted to the vasculature. Therapeutics which are selective for the diseased vasculature are ideal, but whole-body selectivity of a therapeutic is challenging to assess in practice. Vessel myography is used to determine the functional mechanisms and evaluate pharmacological responses of vascularly-targeted therapeutics. However, myography can only be performed on ex vivo sections of individual arteries. We have developed methods for implementation of spherical-view photoacoustic tomography for non-invasive and in vivo myography. Using photoacoustic tomography, we demonstrate the measurement of acute vascular reactivity in the systemic vasculature and the placenta of female pregnant mice in response to two vasodilators. Photoacoustic tomography simultaneously captures the significant acute vasodilation of major arteries and detects selective vasoactivity of the maternal-fetal vasculature. Photoacoustic tomography has the potential to provide invaluable preclinical information on vascular response that cannot be obtained by other established methods.

Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Neural control of the circulation during exercise in heart failure with reduced and preserved ejection fraction.

Patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit severe exercise intolerance that may be due, in part, to inappropriate cardiovascular and hemodynamic adjustments to exercise. Several neural mechanisms and locally released vasoactive substances work in concert through complex interactions to ensure proper adjustments to meet the metabolic demands of the contracting skeletal muscle. Specifically, accumulating evidence suggests that disease-related alterations in neural mechanisms (e.g., central command, exercise pressor reflex, arterial baroreflex, and cardiopulmonary baroreflex) contribute to heightened sympathetic activation and impaired ability to attenuate sympathetic vasoconstrictor responsiveness that may contribute to reduced skeletal muscle blood flow and severe exercise intolerance in patients with HFrEF. In contrast, little is known regarding these important aspects of physiology in patients with HFpEF, though emerging data reveal heightened sympathetic activation and attenuated skeletal muscle blood flow during exercise in this patient population that may be attributable to dysregulated neural control of the circulation. The overall goal of this review is to provide a brief overview of the current understanding of disease-related alterations in the integrative neural cardiovascular responses to exercise in both HFrEF and HFpEF phenotypes, with a focus on sympathetic nervous system regulation during exercise.

A biochemomechanical model of collagen turnover in arterial adaptations to hemodynamic loading.

The production, removal, and remodeling of fibrillar collagen is fundamental to mechanical homeostasis in arteries, including dynamic morphological and microstructural changes that occur in response to sustained changes in blood flow and pressure under physiological conditions. These dynamic processes involve complex, coupled biological, chemical, and mechanical mechanisms that are not completely understood. Nevertheless, recent simulations using constrained mixture models with phenomenologically motivated constitutive relations have proven able to predict salient features of the progression of certain vascular adaptations as well as disease processes. Collagen turnover is modeled, in part, via stress-dependent changes in collagen half-life, typically within the range of 10-70 days. By contrast, in this work we introduce a biochemomechanical approach to model the cellular synthesis of procollagen as well as its transition from an intermediate state of assembled microfibrils to mature cross-linked fibers, with mechano-regulated removal. The resulting model can simulate temporal changes in geometry, composition, and stress during early vascular adaptation (weeks to months) for modest changes in blood flow or pressure. It is shown that these simulations capture salient features from data presented in the literature from different animal models.

Modeling essential hypertension with a closed-loop mathematical model for the entire human circulation.

Arterial hypertension, defined as an increase in systemic arterial pressure, is a major risk factor for the development of diseases affecting the cardiovascular system. Every year, 9.4 million deaths worldwide are caused by complications arising from hypertension. Despite well-established approaches to diagnosis and treatment, fewer than half of all hypertensive patients have adequately controlled blood pressure. In this scenario, computational models of hypertension can be a practical approach for better quantifying the role played by different components of the cardiovascular system in the determination of this condition. In the present work we adopt a global closed-loop multi-scale mathematical model for the entire human circulation to reproduce a hypertensive scenario. In particular, we modify the model to reproduce alterations in the cardiovascular system that are cause and/or consequence of the hypertensive state. The adaptation does not only affect large systemic arteries and the heart but also the microcirculation, the pulmonary circulation and the venous system. Model outputs for the hypertensive scenario are validated through assessment of computational results against current knowledge on the impact of hypertension on the cardiovascular system.

A spatially resolved timeline of the human maternal-fetal interface.

Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR)1-3. However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal-fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.

Remodeling of the cardiovascular hemodynamic environment by lower limb heat exposure: A computational fluid dynamic study.

BACKGROUND: Lower limb heat exposure (LLHE) is a promising strategy for the daily management of cardiovascular health because of its non-pharmaceutical advantages. To support the application of this strategy in cardiovascular protection, we examined its impact on the global hemodynamic environment. METHODS: Skin blood flow (SBF) of eight locations on the lower limbs was measured before and after LLHE (40 °C and 44 °C) in ten healthy subjects by using a laser Doppler flowmeter. A closed-loop model of circulation uses changes in SBF to quantify the influence of LLHE on the blood flow of the arterial trunk (from ascending aorta to the femoral artery) and visceral branches (coronary, celiac, renal, and mesenteric arteries). RESULTS: The SBF in all locations tested on the lower limbs increased significantly (p<0.001) with LLHE and a 3.39-fold and 7.40-fold increase in mean SBF were observed under 40 °C and 44 °C conditions, respectively. In the model, the peak (3.9-25.1%), end-diastolic (13.7-107.3%), and mean blood flow (8.5-86.5%) in the arterial trunk increased with the increase in temperature, but the retrograde flow in the thoracic aorta and abdominal aorta Ⅰ increased at least twice in the diastolic period. Furthermore, LLHE also increased the blood flow of the visceral branches (2.5-20.7%). CONCLUSION: These findings suggest that LLHE is expected to be a daily strategy for enhancing the functions of both the arterial trunk and visceral arteries, but the increased blood flow reversal in the thoracic and abdominal aortas warrants further investigation.

Development and characterization of canine-specific computational models to predict pulsatile arterial hemodynamics and ventricular-arterial coupling.

Pulsatile hemodynamics analyses provide important information about the ventricular-arterial system which cannot be inferred by standard blood pressure measurements. Pulse wave analysis (PWA), wave separation analysis (WSA), and wave power analysis (WPA) characterize arterial hemodynamics with limited preclinical applications. Integrating these tools into preclinical testing may enhance understanding of disease or therapeutic effects on cardiovascular function. We used a canine rapid ventricular pacing (RVP) heart failure model to: (1) Characterize hemodynamics in response to RVP and (2) assess analyses from flow waveforms synthesized from pressure compared to those derived from measured flow. Female canines (n = 7) were instrumented with thoracic aortic pressure transducers, ventricular pacing leads, and an ascending aortic flow probe. Data were collected at baseline, 1 week, and 1 month after RVP onset. RVP progressively reduced stroke volume (SV), the PWA SV estimator, and WSA and WPA pulsatility and wave reflection indices. Indices derived from synthesized flow exhibited similar directional changes and high concordance with measured flow calculations. Our data demonstrate the value of analytical hemodynamic methods to gain deeper insight into cardiovascular function in preclinical models. These approaches can provide complementary value to standard endpoints in evaluating potential effects of pharmaceutical agents intended for human use.

A Vector Fitting Approach for the Automated Estimation of Lumped Boundary Conditions of 1D Circulation Models.

PURPOSE: The choice of appropriate boundary conditions is a crucial step in the development of cardiovascular models for blood flow simulations. The three-element Windkessel model is usually employed as a lumped boundary condition, providing a reduced order representation of the peripheral circulation. However, the systematic estimation of the Windkessel parameters remains an open problem. Moreover, the Windkessel model is not always adequate to model blood flow dynamics, which often require more elaborate boundary conditions. In this study, we propose a method for the estimation of the parameters of high order boundary conditions, including the Windkessel model, from pressure and flow rate waveforms at the truncation point. Moreover, we investigate the effect of adopting higher order boundary conditions, corresponding to equivalent circuits with more than one storage element, on the accuracy of the model. METHOD: The proposed technique is based on Time-Domain Vector Fitting, a modeling algorithm that, given samples of the input and output of a system, such as pressure and flow waveforms, can derive a differential equation approximating their relation. RESULTS: The capabilities of the proposed method are tested on a 1D circulation model consisting of the 55 largest human systemic arteries, to demonstrate its accuracy and its usefulness to estimate boundary conditions with order higher than the traditional Windkessel models. The proposed method is compared to other common estimation techniques, and its robustness in parameter estimation is verified in presence of noisy data and of physiological changes of aortic flow rate induced by mental stress. CONCLUSION: Results suggest that the proposed method is able to accurately estimate boundary conditions of arbitrary order. Higher order boundary conditions can improve the accuracy of cardiovascular simulations, and Time-Domain Vector Fitting can automatically estimate them.

Endurance-trained subjects and sedentary controls increase ventricular contractility and efficiency during exercise: Feasibility of hemodynamics assessed by non-invasive pressure-volume loops.

INTRODUCTION: Pressure-volume (PV) loops can be used to assess both load-dependent and load-independent measures of cardiac hemodynamics. However, analysis of PV loops during exercise is challenging as it requires invasive measures. Using a novel method, it has been shown that left ventricular (LV) PV loops at rest can be obtained non-invasively from cardiac magnetic resonance imaging (CMR) and brachial pressures. Therefore, the aim of this study was to assess if LV PV loops can be obtained non-invasively from CMR during exercise to assess cardiac hemodynamics. METHODS: Thirteen endurance trained (ET; median 48 years [IQR 34-60]) and ten age and sex matched sedentary controls (SC; 43 years [27-57]) were included. CMR images were acquired at rest and during moderate intensity supine exercise defined as 60% of expected maximal heart rate. Brachial pressures were obtained in conjunction with image acquisition. RESULTS: Contractility measured as maximal ventricular elastance (Emax) increased in both groups during exercise (ET: 1.0 mmHg/ml [0.9-1.1] to 1.1 mmHg/ml [0.9-1.2], p<0.01; SC: 1.1 mmHg/ml [0.9-1.2] to 1.2 mmHg/ml [1.0-1.3], p<0.01). Ventricular efficiency (VE) increased in ET from 70% [66-73] at rest to 78% [75-80] (p<0.01) during exercise and in SC from 68% [63-72] to 75% [73-78] (p<0.01). Arterial elastance (EA) decreased in both groups (ET: 0.8 mmHg/ml [0.7-0.9] to 0.7 mmHg/ml [0.7-0.9], p<0.05; SC: 1.0 mmHg/ml [0.9-1.2] to 0.9 mmHg/ml [0.8-1.0], p<0.05). Ventricular-arterial coupling (EA/Emax) also decreased in both groups (ET: 0.9 [0.8-1.0] to 0.7 [0.6-0.8], p<0.01; SC: 1.0 [0.9-1.1] to 0.7 [0.7-0.8], p<0.01). CONCLUSIONS: This study demonstrates for the first time that LV PV loops can be generated non-invasively during exercise using CMR. ET and SC increase ventricular efficiency and contractility and decrease afterload and ventricular-arterial coupling during moderate supine exercise. These results confirm known physiology. Therefore, this novel method is applicable to be used during exercise in different cardiac disease states, which has not been possible non-invasively before.