Arterial pulse wave modeling and analysis for vascular-age studies: a review from VascAgeNet.

Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.

Lower limb hyperthermia augments functional hyperaemia during small muscle mass exercise similarly in trained elderly and young humans.

NEW FINDINGS: What is the central question of the study? Ageing is postulated to lead to underperfusion of human limb tissues during passive and exertional hyperthermia, but findings to date have been equivocal. Thus, does age have an independent adverse effect on local haemodynamics during passive single-leg hyperthermia, single-leg knee-extensor exercise and their combination? What is the main finding and its importance? Local hyperthermia increased leg blood flow over three-fold and had an additive effect during knee-extensor exercise with no absolute differences in leg perfusion between the healthy, exercise-trained elderly and the young groups. Our findings indicate that age per se does not compromise lower limb hyperaemia during local hyperthermia and/or small muscle mass exercise. ABSTRACT: Heat and exercise therapies are recommended to improve vascular health across the lifespan. However, the haemodynamic effects of hyperthermia, exercise and their combination are inconsistent in young and elderly people. Here we investigated the acute effects of local-limb hyperthermia and exercise on limb haemodynamics in nine healthy, trained elderly (69 ± 5 years) and 10 young (26 ± 7 years) adults, hypothesising that the combination of local hyperthermia and exercise interact to increase leg perfusion, albeit to a lesser extent in the elderly. Participants underwent 90 min of single whole-leg heating, with the contralateral leg remaining as control, followed by 10 min of low-intensity incremental single-leg knee-extensor exercise with both the heated and control legs. Temperature profiles and leg haemodynamics at the femoral and popliteal arteries were measured. In both groups, heating increased whole-leg skin temperature and blood flow by 9.5 ± 1.2°C and 0.7 ± 0.2 L min-1 (>3-fold), respectively (P < 0.0001). Blood flow in the heated leg remained 0.7 ± 0.6 and 1.0 ± 0.8 L min-1 higher during exercise at 6 and 12 W, respectively (P < 0.0001). However, there were no differences in limb haemodynamics between cohorts, other than the elderly group exhibiting a 16 ± 6% larger arterial diameter and a 51 ± 6% lower blood velocity following heating (P < 0.0001). In conclusion, local hyperthermia-induced limb hyperperfusion and/or small muscle mass exercise hyperaemia are preserved in trained older people despite evident age-related structural and functional alterations in their leg conduit arteries.

Experimental Devices Versus Hand-Sewn Anastomosis of the Aorta: A Systematic Review and Meta-Analysis.

BACKGROUND: To minimize complications associated with the construction of the hand-sewn aortic anastomosis, alternative experimental methods have been pursued. This study aimed to evaluate the efficacy of experimental anastomotic devices in relation to time and point of rupture of the anastomosis in comparison to the conventional technique. MATERIALS AND METHODS: An electronic search was performed using MEDLINE, Scopus, Science Direct, and Cochrane Library databases by two independent authors. Our exclusion criteria referred to studies reporting results solely from end-to-side anastomosis, results on vessels other than the aorta, studies that did not involve animal experiments, and non-English publications. The last search date was January 1, 2020. RESULTS: The meta-analysis included 22 studies with 34 anastomosis samples and a total of 316 animals. The pooled mean automated anastomosis time was 10.38 min, and the mean point of rupture was 32.7 N. In the subgroup analysis of automated anastomosis time by device category, the anastomotic stenting technique reported significantly lower anastomosis time but also showed significantly lower point of rupture. Comparing the efficacy of experimental devices and the hand-sewn technique, our pooled analysis showed that automated devices significantly decrease the time needed to perform the anastomosis (weighted mean difference -7.24 min). On the other hand, the automated anastomosis is also associated with decreased tensile strength (weighted mean difference -20.68 N). CONCLUSIONS: Although experimental devices seem to offer a faster anastomosis, they lack endurance when compared with the hand-sewn technique. Further research is needed for the development of an "ideal" anastomotic technique.

Carotid artery wave intensity in mid- to late-life predicts cognitive decline: the Whitehall II study.

AIMS: Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent cognitive decline. METHODS AND RESULTS: Duplex Doppler ultrasound was used to calculate peak forward-travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean ± standard deviation (SD), age = 61 ± 6 years; 75% male] assessed as part of the Whitehall II study in 2003-05. Serial measures of cognitive function were taken between 2002-04 and 2015-16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was -0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI = -0.02 (95% confidence interval -0.04 to -0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1-Q3 = -0.05 (-0.09 to -0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was ∼50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17-1.88)]. CONCLUSION: Elevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors.

Newly Shaped Intra-Aortic Balloons Improve the Performance of Counterpulsation at the Semirecumbent Position: An In Vitro Study.

The major hemodynamic benefits of intra-aortic balloon pump (IABP) counterpulsation are augmentation in diastolic aortic pressure (Paug ) during inflation, and decrease in end-diastolic aortic pressure (ΔedP) during deflation. When the patient is nursed in the semirecumbent position these benefits are diminished. Attempts to change the shape of the IAB in order to limit or prevent this deterioration have been scarce. The aim of the present study was to investigate the hemodynamic performance of six new IAB shapes, and compare it to that of a traditional cylindrical IAB. A mock circulation system, featuring an artificial left ventricle and an aortic model with 11 branches and physiological resistance and compliance, was used to test one cylindrical and six newly shaped IABs at angles 0, 10, 20, 30, and 40°. Pressure was measured continuously at the aortic root during 1:1 and 1:4 IABP support. Shape 2 was found to consistently achieve, in terms of absolute magnitude, larger ΔedP at angles than the cylindrical IAB. Although ΔedP was gradually diminished with angle, it did so to a lesser degree than the cylindrical IAB; this diminishment was only 53% (with frequency 1:1) and 40% (with frequency 1:4) of that of the cylindrical IAB, when angle increased from 0 to 40°. During inflation Shape 1 displayed a more stable behavior with increasing angle compared to the cylindrical IAB; with an increase in angle from 0 to 40°, diastolic aortic pressure augmentation dropped only by 45% (with frequency 1:1) and by 33% (with frequency 1:4) of the drop reached with the cylindrical IAB. After compensating for differences in nominal IAB volume, Shape 1 generally achieved higher Paug over most angles. Newly shaped IABs could allow for IABP therapy to become more efficient for patients nursed at the semirecumbent position. The findings promote the idea of personalized rather than generalized patient therapy for the achievement of higher IABP therapeutic efficiency, with a choice of IAB shape that prioritizes the recovery of those hemodynamic indices that are more in need of support in the unassisted circulation.

Measurements of Intra-Aortic Balloon Wall Movement During Inflation and Deflation: Effects of Angulation.

The intra-aortic balloon pump (IABP) is a ventricular assist device that is used with a broad range of pre-, intra-, and postoperative patients undergoing cardiac surgery. Although the clinical efficacy of the IABP is well documented, the question of reduced efficacy when patients are nursed in the semi-recumbent position remains outstanding. The aim of the present work is therefore to investigate the underlying mechanics responsible for the loss of IABP performance when operated at an angle to the horizontal. Simultaneous recordings of balloon wall movement, providing an estimate of its diameter (D), and fluid pressure were taken at three sites along the intra-aortic balloon (IAB) at 0 and 45°. Flow rate, used for the calculation of displaced volume, was also recorded distal to the tip of the balloon. An in vitro experimental setup was used, featuring physiological impedances on either side of the IAB ends. IAB inflation at an angle of 45° showed that D increases at the tip of the IAB first, presenting a resistance to the flow displaced away from the tip of the balloon. The duration of inflation decreased by 15.5%, the inflation pressure pulse decreased by 9.6%, and volume decreased by 2.5%. Similarly, changing the position of the balloon from 0 to 45°, the balloon deflation became slower by 35%, deflation pressure pulse decreased by 14.7%, and volume suctioned was decreased by 15.2%. IAB wall movement showed that operating at 45° results in slower deflation compared with 0°. Slow wall movement, and changes in inflation and deflation onsets, result in a decreased volume displacement and pressure pulse generation. Operating the balloon at an angle to the horizontal, which is the preferred nursing position in intensive care units, results in reduced IAB inflation and deflation performance, possibly compromising its clinical benefits.

Manufacturing an artificial arterial tree using 3D printing.

Models of the arterial network are useful in studying mechanical cardiac assist devices as well as complex pathological states that are difficult to investigate in-vivo otherwise. Earlier work of artificial arterial tree (AAT) have been constructed to include some of the major arteries and their branches for in-vitro experiments which focused on the aorta, using dipping or painting techniques, which resulted in inaccuracies and inconsistent wall thickness. Therefore, the aim of this work is to use 3D printing for manufacturing AAT based on physiologically correct dimensions of the largest 45 segments of the human arterial tree. A volume ratio mix of silicone rubber (98 %) and a catalyst (2 %) was used to create the walls of the AAT. To validate, the AAT was connected at its inlet to a piston pump that mimicked the heart and capillary tubes at the outlets that mimicked arterial resistances. The capillary tubes were connected to a reservoir that collected the water which was the fluid used in testing the closed-loop hydraulic system. Young's modulus of the AAT walls was determined using tensile testing of different segments of various wall thickness. The developed AAT produced pressure, diameter and flow rate waveforms that are similar to those observed in-vivo. The technique described here is low cost, may be used for producing arterial trees to facilitate testing mechanical cardiac assist devices and studying hemodynamic investigations.

A comparison of different methods to maximise signal extraction when using central venous pressure to optimise atrioventricular delay after cardiac surgery.

Objective: Our group has shown that central venous pressure (CVP) can optimise atrioventricular (AV) delay in temporary pacing (TP) after cardiac surgery. However, the signal-to-noise ratio (SNR) is influenced both by the methods used to mitigate the pressure effects of respiration and the number of heartbeats analysed. This paper systematically studies the effect of different analysis methods on SNR to maximise the accuracy of this technique. Methods: We optimised AV delay in 16 patients with TP after cardiac surgery. Transitioning rapidly and repeatedly from a reference AV delay to different tested AV delays, we measured pressure differences before and after each transition. We analysed the resultant signals in different ways with the aim of maximising the SNR: (1) adjusting averaging window location (around versus after transition), (2) modifying window length (heartbeats analysed), and (3) applying different signal filtering methods to correct respiratory artefact. Results: (1) The SNR was 27 % higher for averaging windows around the transition versus post-transition windows. (2) The optimal window length for CVP analysis was two respiratory cycle lengths versus one respiratory cycle length for optimising SNR for arterial blood pressure (ABP) signals. (3) Filtering with discrete wavelet transform improved SNR by 62 % for CVP measurements. When applying the optimal window length and filtering techniques, the correlation between ABP and CVP peak optima exceeded that of a single cycle length (R = 0.71 vs. R = 0.50, p < 0.001). Conclusion: We demonstrated that utilising a specific set of techniques maximises the signal-to-noise ratio and hence the utility of this technique.

The contribution of upper and lower body arterial vessels to the aortic root reflections: A one-dimensional computational study.

BACKGROUND AND OBJECTIVES: Reflections measured at the aortic root are of physiological and clinical interest and thought to be composed of the superimposed reflections arriving from the upper and lower parts of the circulatory system. However, the specific contribution of each region to the overall reflection measurement has not been thoroughly examined. This study aims to elucidate the relative contribution of reflected waves arising from the upper and lower human body vasculature to those observed at the aortic root. METHODS: We utilised a one-dimensional (1D) computational model of wave propagation to study reflections in an arterial model that included 37 largest arteries. A narrow Gaussian-shaped pulse was introduced to the arterial model from five distal locations: carotid, brachial, radial, renal, and anterior tibial. The propagation of each pulse towards the ascending aorta was computationally tracked. We calculated the reflected pressure and wave intensity at the ascending aorta in each case. The results are presented as a ratio of the initial pulse. RESULTS: The findings of this study indicates that pressure pulses originated at the lower body can hardly be observed, while those originated from the upper body account for the largest portion of reflected waves seen at the ascending aorta. CONCLUSIONS: Our study validates the findings of earlier studies, which demonstrated that human arterial bifurcations have a significantly lower reflection coefficient in the forward direction as compared to the backward direction. The results of this study underscore the need for further in-vivo investigations to provide a deeper understanding of the nature and characteristics of reflections observed in the ascending aorta, which can inform the development of effective strategies for the management of arterial diseases.

A mock circulatory system with physiological distribution of terminal resistance and compliance: application for testing the intra-aortic balloon pump.

A mock circulatory system (MCS) was designed to replicate a physiological environment for in vitro testing and was assessed with the intra-aortic balloon pump (IABP). The MCS was comprised of an artificial left ventricle (LV), connected to a 14-branch polyurethane-compound aortic model. Physiological distribution of terminal resistance and compliance according to published data was implemented with capillary tubes of different sizes and syringes of varying air volume, respectively, fitted at the outlets of the branches. The ends of the aortic branches were connected to a common tube representing the venous system and an overhead reservoir provided atrial pressure. An IABP operating a 40-cc balloon was set to counterpulsate with the LV. Total arterial compliance of the system was 0.94 mL/mm Hg and total arterial resistance was 20.3 ± 3.3 mm Hg/L/min. At control, physiological flow distribution was achieved and both mean and phasic aortic pressure and flow were physiological. With the IABP, aortic pressure exhibited the major features of counterpulsation: diastolic augmentation during inflation, inflection point at onset of deflation, and end-diastolic reduction at the end of deflation. The contribution of balloon inflation and deflation was also evident on the aortic flow pattern. This MCS was verified to be suitable for IABP testing and with further adaptations it could be used for studying other hemodynamic problems and ventricular assist devices.

Time-course of the human thoracic aorta ageing process assessed using uniaxial mechanical testing and constitutive modelling.

Age-related remodelling of the arterial wall shifts the load bearing from the compliant elastin network to the stiffer collagen fibres. While this phenomenon has been widely investigated in animal models, human studies are lacking due to shortage of donors' arteries. This work aimed to characterise the effect of ageing on the mechanical properties of the human aortic wall in the circumferential direction. N = 127 thoracic aortic rings (age 18-81 years) were subjected to circumferential tensile testing. The tangential elastic modulus (Kθθθθ) was calculated at pressure-equivalent stresses ranging 60-100 mmHg. Further, the mechanical data were fitted using the Holzpafel-Gasser-Ogden hyperelastic strain energy function (HGO-SEF), modelling the superimposed response of an isotropic matrix (elastin) reinforced by collagen fibres. Kθθθθ increased with age across at all considered pressures (p < 0.001), although more strongly at higher pressures. Indeed, the slope of the linear Kθθθθ-pressure relationship increased by 300% from donors <30 to ≥70 years (4.72± 2.95 to 19.06± 6.82 kPa/mmHg, p < 0.001). The HGO-SEF elastin stiffness-like parameter dropped by 31% between 30 and 40 years (p < 0.05) with non-significant changes thereafter. Conversely, changes in HGO-SEF collagen parameters were observed later at age>60 years, with the exponential constant increasing by ∼20-50 times in the investigated age range (p < 0.001). The results provided evidence that the human thoracic aorta undergoes stiffening during its life-course. Constitutive modelling suggested that these changes in arterial mechanics are related to the different degeneration time-courses of elastin and collagen; likely due to considerable fragmentation of elastin first, with the load bearing shifting from the compliant elastin to the stiffer collagen fibres. This process leads to a gradual impairment of the aortic elastic function with age.

Techniques to aid prediction of pacing dependence at 30 days in patients requiring pacemaker implantation after cardiac surgery.

Permanent pacemaker (PPM) implantation occurs in up to 5 % of patients after cardiac surgery but there is little consensus on how long to wait between surgery and PPM insertion. Predicting the likelihood of a patient being pacing dependent 30 days after implant can aid with this timing decision and avoid unnecessary observation time waiting for intrinsic conduction to recover. In this paper, we introduce a new approach for the prediction of PPM dependency at 30 days after implant in patients who have undergone recent cardiac surgery. The aim is to create an automatic detection model able to support clinicians in the decision-making process. We first applied Synthetic Minority Oversampling Technique (SMOTE) and Bayesian Networks (BN) to the dataset, to balance the inherently imbalanced data and create additional synthetic data respectively. The six resultant datasets were then used to train four different classifiers to predict pacing dependence at 30 days, all using the same testing set. The Bagged Trees classifier achieved the best results, reaching an area under the receiver operating curve (AUC) of 90 % in the train phase, and 83 % in the test phase. The overall classification performance was clearly enhanced when using SMOTE and synthetic data created with BN to create a combined and balanced dataset. This technique could be of great use in answering clinical questions where the original dataset is imbalanced.

Hybrid model analysis of intra-aortic balloon pump performance as a function of ventricular and circulatory parameters.

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks.

Impact of tapering of arterial vessels on blood pressure, pulse wave velocity, and wave intensity analysis using one-dimensional computational model.

The angle of arterial tapering increases with ageing, and the geometrical changes of the aorta may cause an increase in central arterial pressure and stiffness. The impact of tapering has been primarily studied using frequency-domain transmission line theories. In this work, we revisit the problem of tapering and investigate its effect on blood pressure and pulse wave velocity (PWV) using a time-domain analysis with a 1D computational model. First, tapering is modelled as a stepwise reduction in diameter and compared with results from a continuously tapered segment. Next, we studied wave reflections in a combination of stepwise diameter reduction of straight vessels and bifurcations, then repeated the experiments with decreasing the length to physiological values. As the model's segments became shorter in length, wave reflections and re-reflections resulted in waves overlapping in time. We extended our work by examining the effect of increasing the tapering angle on blood pressure and wave intensity in physiological models: a model of the thoracic aorta and a model of upper thoracic and descending aorta connected to the iliac bifurcation. Vessels tapering inherently changed the ratio between the inlet and outlet cross-sectional areas, increasing the vessel resistance and reducing the compliance compared with non-tapered vessels. These variables influence peak and pulse pressure. In addition, it is well established that pulse wave velocity increases in an ageing arterial tree. This work provides confirmation that tapering induces reflections and offers an additional explanation to the observation of increased peak pressure and decreased diastolic pressure distally in the arterial tree.

Review of the Techniques Used for Investigating the Role Elastin and Collagen Play in Arterial Wall Mechanics.

The arterial wall is characterised by a complex microstructure that impacts the mechanical properties of the vascular tissue. The main components consist of collagen and elastin fibres, proteoglycans, Vascular Smooth Muscle Cells (VSMCs) and ground matrix. While VSMCs play a key role in the active mechanical response of arteries, collagen and elastin determine the passive mechanics. Several experimental methods have been designed to investigate the role of these structural proteins in determining the passive mechanics of the arterial wall. Microscopy imaging of load-free or fixed samples provides useful information on the structure-function coupling of the vascular tissue, and mechanical testing provides information on the mechanical role of collagen and elastin networks. However, when these techniques are used separately, they fail to provide a full picture of the arterial micromechanics. More recently, advances in imaging techniques have allowed combining both methods, thus dynamically imaging the sample while loaded in a pseudo-physiological way, and overcoming the limitation of using either of the two methods separately. The present review aims at describing the techniques currently available to researchers for the investigation of the arterial wall micromechanics. This review also aims to elucidate the current understanding of arterial mechanics and identify some research gaps.

Towards the non-invasive determination of arterial wall distensible properties: New approach using old formulae.

Arterial function and wall mechanical properties are important determinants of hemodynamics in the circulation. However, their non-invasive determination is not widely available. Therefore, the aim of this work is to present a novel approach for the non-invasive determination of vessel's distensibility and elastic modulus. Simultaneous measurements of vessel's Diameter (D) and flow velocity (U) were recorded to determine local wave speed (nC) in flexible tubes and calf aortas non-invasively using the lnDU-loop method, which was used to calculate the Distensibility (nDs) and Elastic Modulus (nE), also non-invasively. To validate the new approach, the non-invasive results were compared to traditionally invasive measurements of Dynamic Distensibility (Dsd) and Tangential Elastic Modulus (Em). In flexible tubes, the average nDs was higher and nE was lower than Dsd and Em by 1.6% and 6.9%, respectively. In calf aortas, the results of nDs and nE agreed well with those of Dsd and Em, as demonstrated by Bland-Altman technique. The results of nDs and nE are comparable to those determined using traditional techniques. Our results suggest that nDs and nE could be measured in-vivo non-invasively, given the possibility of measuring D and U to obtain nC. Further studies are warranted to establish the clinical usefulness of the new approach.

From Uniaxial Testing of Isolated Layers to a Tri-Layered Arterial Wall: A Novel Constitutive Modelling Framework.

Mechanical testing and constitutive modelling of isolated arterial layers yields insight into the individual layers' mechanical properties, but per se fails to recapitulate the in vivo loading state, neglecting layer-specific residual stresses. The aim of this study was to develop a testing/modelling framework that integrates layer-specific uniaxial testing data into a three-layered model of the arterial wall, thereby enabling study of layer-specific mechanics under realistic (patho)physiological conditions. Circumferentially and axially oriented strips of pig thoracic aortas (n = 10) were tested uniaxially. Individual arterial layers were then isolated from the wall, tested, and their mechanical behaviour modelled using a hyperelastic strain energy function. Subsequently, the three layers were computationally assembled into a single flat-walled sample, deformed into a cylindrical vessel, and subjected to physiological tension-inflation. At the in vivo axial stretch of 1.10 ± 0.03, average circumferential wall stress was 75 ± 9 kPa at 100 mmHg, which almost doubled to 138 ± 15 kPa at 160 mmHg. A ~ 200% stiffening of the adventitia over the 60 mmHg pressure increase shifted layer-specific load-bearing from the media (65 ± 10% → 61 ± 14%) to the adventitia (28 ± 9% → 32 ± 14%). Our approach provides valuable insight into the (patho)physiological mechanical roles of individual arterial layers at different loading states, and can be implemented conveniently using simple, inexpensive and widely available uniaxial testing equipment.

Mock circulatory loops used for testing cardiac assist devices: A review of computational and experimental models.

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD's performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.

Regional thermal hyperemia in the human leg: Evidence of the importance of thermosensitive mechanisms in the control of the peripheral circulation.

Hyperthermia is thought to increase limb blood flow through the activation of thermosensitive mechanisms within the limb vasculature, but the precise vascular locus in which hyperthermia modulates perfusion remains elusive. We tested the hypothesis that local temperature-sensitive mechanisms alter limb hemodynamics by regulating microvascular blood flow. Temperature and oxygenation profiles and leg hemodynamics of the common (CFA), superficial (SFA) and profunda (PFA) femoral arteries, and popliteal artery (POA) of the experimental and control legs were measured in healthy participants during: (1) 3 h of whole leg heating (WLH) followed by 3 h of recovery (n = 9); (2) 1 h of upper leg heating (ULH) followed by 30 min of cooling and 1 h ULH bout (n = 8); and (3) 1 h of lower leg heating (LLH) (n = 8). WLH increased experimental leg temperature by 4.2 ± 1.2ºC and blood flow in CFA, SFA, PFA, and POA by ≥3-fold, while the core temperature essentially remained stable. Upper and lower leg blood flow increased exponentially in response to leg temperature and then declined during recovery. ULH and LLH similarly increased the corresponding segmental leg temperature, blood flow, and tissue oxygenation without affecting these responses in the non-heated leg segment, or perfusion pressure and conduit artery diameter across all vessels. Findings demonstrate that whole leg hyperthermia induces profound and sustained elevations in upper and lower limb blood flow and that segmental hyperthermia matches the regional thermal hyperemia without causing thermal or hemodynamic alterations in the non-heated limb segment. These observations support the notion that heat-activated thermosensitive mechanisms in microcirculation regulate limb tissue perfusion during hyperthermia.

Five years of cardio-ankle vascular index (CAVI) and CAVI0: how close are we to a pressure-independent index of arterial stiffness?

Pulse wave velocity, a common metric of arterial stiffness, is an established predictor for cardiovascular events and mortality. However, its intrinsic pressure-dependency complicates the discrimination of acute and chronic impacts of increased blood pressure on arterial stiffness. Cardio-ankle vascular index (CAVI) represented a significant step towards the development of a pressure-independent arterial stiffness metric. However, some potential limitations of CAVI might render this arterial stiffness metric less pressure-independent than originally thought. For this reason, we later introduced CAVI0. Nevertheless, advantages of one approach over the other are left debated. This review aims to shed light on the pressure (in)dependency of both CAVI and CAVI0. By critically reviewing results from studies reporting both CAVI and CAVI0 and using simple analytical methods, we show that CAVI0 may enhance the pressure-independent assessment of arterial stiffness, especially in the presence of large inter-individual differences in blood pressure.