Evaluation of ivermectin and vitamin E based combination with antiseizure rufinamide drug for mitigation of pentylenetetrazole-induced kindling, behavioral challenges and histopathological aberrations.

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.

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.

Anxiolytic potential of resveratrol and rufinamide combination by modulating GABA-ergic transmission: insights from experiments, molecular docking and dynamics simulations.

Resveratrol is a polyphenolic phytocompound known to possess anxiolytic-like effects but its impact on central gammaaminobutyric acid (GABA) modulation has never been explored. The purpose of this study was to analyze the anxiolytic-like effects of resveratrol alone and in combination with rufinamide, an antiepileptic drug which has never been studied for its anxiolytic potential. The BALB/c mice were tested in a battery of behavior testing after administration of resveratrol (50 mg/kg) and rufinamide (50 mg/kg) alone and in combination. Moreover, molecular docking studies were also carried out to understand the interaction of resveratrol and rufinamide with GABA aminotransferase, GABA receptor and GABA-A transporter type 1. Resveratrol alone exerted notable anxiolytic-like effects and improved outcomes in few experiments but rufinamide alone did not yield any beneficial outcomes. However, the animal co-administered with resveratrol and rufinamide behaved exceptionally well (p<0.05) and preferred open, illuminated and exposed areas of open field, light/dark and elevated plus maze. Further, these animals showed reduced anxiety towards anxiogenic stimuli i.e. holes and marbles in hole board and marble bury tests, respectively. Resveratrol and rufinamide showed moderate to strong binding affinities with GABA proteins, indicating the potential to treat anxiety-like neurological disorders. Moreover, resveratrol and rufinamide were analyzed using molecular docking to determine their interaction with GABA receptors, transporters, and transaminase. The results suggest that their anxiolytic-like effects may be due to inhibiting GABA reuptake transporter 1 protein, leading to increased synaptic levels of GABA neurotransmitter, as seen in stable molecular dynamics results with the 7SK2 GABA transporter protein.

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.

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.

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.

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.

Infective Endocarditis as a Cause of Critical Illness, In-hospital Mortality, and Complications.

Background: Critical illness due to infective endocarditis (IE) has high in-hospital mortality. Besides being a cause of sepsis, this disease has the potential nature to affect multiple organs. Patients and methods: Data for 84 patients managed at the critical care medicine unit at Cairo University for 7 years were surveyed for IE using modified Dukes criteria. Among the patient group with a verified diagnosis of IE, patient characteristics (age and comorbidities), the grade of diagnosis, the blood culture result, echocardiographic findings, minor diagnostic signs (fever, presence of prosthetic valves and pacemaker, vascular phenomena, immunologic phenomena) and clinical complications (heart failure, septic shock, neurologic complications renal failure) were studied regarding their association to in-hospital mortality. Incidence of clinical complications was compared to the control group with sepsis due to other causes. Results: The mortality rate in the IE group is 18.8%. Factors showing significant association to in-hospital mortality are; septic shock p = 0.01, neurological complications p = 0.025 (especially cerebral hemorrhage p = 0.025), indicated non-performed surgery p = 0.008, and presence of underlying heart failure with reduced ejection fraction (HFrEF), p = 0.002. Incidence of clinical complications showed no significant difference in IE patients and patients with other causes of sepsis except heart failure which showed significantly increased incidence in the IE group, p = 0.004. Conclusion: Septic shock, neurological complications, indicated nonperformed surgery, and presence of underlying HFrEF are in-hospital mortality risk factors in critically ill patients due to IE. In-hospital mortality and clinical complication incidence (except heart failure) are similar to other causes of sepsis. How to cite this article: Ayad RD, Andraos AW, Taema KAE, Attia IM, Yehia M. Infective Endocarditis as a Cause of Critical Illness, In-hospital Mortality, and Complications. Indian J Crit Care Med 2022;26(8):930-934.

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.

Noninvasive carotid pressure-diameter loops to identify viscoelastic properties in ageing, hypertension and type 2 diabetes.

OBJECTIVES: Arterial stiffness as pulse wave velocity (PWV) predicts cardiovascular events independently of blood pressure (BP). PWV does not distinguish between stiffness in systole and diastole. This cross-sectional study aimed to test the hypothesis that viscous and elastic carotid wall properties differ between systole and diastole, distinguishing effects of ageing, hypertension and T2 diabetes (T2DM). METHODS: We examined carotid visco-elasticity in 307 people (180 men), with hypertension alone (n = 69), combined hypertension/T2DM (H-T2DM, n = 99), normotensive (N-T2DM, n = 25) and healthy controls (n = 114). Diameter (D)/pressure (P) waveforms were measured at right /left common carotid arteries, respectively. Local carotid PWV and distensibility in systole and diastole were evaluated by the D2P-loop method, and wall viscosity from hysteresis, the area (HA) within the P--D loop, as a dynamic measure of systolic loading and diastolic unloading. RESULTS: Controls' hysteresis fell quadratically with age (R2 = 0.23, P < 0.001). Yet mean HA in hypertensive patients (0.95, 95% CI 0.65-1.23) was six-fold higher than in age-matched controls (0.14, -0.20 to 0.49, P < 0.001) with a 2.5× difference between diastolic (dDs) to systolic (sDs) distensibility (P < 0.05) in hypertensive patients. HA was higher in hypertensive patients and H-T2DMs (0.80, 0.58-1.04) than N-T2DMs (0.20, -0.17 to 0.54, P < 0.05), but similar between controls and N-T2DMs. BP-adjusted carotid diameters in all T2DM were significantly greater compared with controls and hypertensive patients. CONCLUSION: Higher BP increased wall viscosity, hysteresis and relative difference between systolic and diastolic distensibility across groups. Carotid diameters were increased in all T2DMs, more in H-T2DM, probably altering BP-flow dynamics in T2DM.

Transfer-function-free technique for the noninvasive determination of the human arterial pressure waveform.

The estimation of central aortic blood pressure is a cardinal measurement, carrying effective physiological, and prognostic data beyond routine peripheral blood pressure. Transfer function-based devices effectively estimate aortic systolic and diastolic blood pressure from peripheral pressure waveforms, but the reconstructed pressure waveform seems to preserve features of the peripheral waveform. We sought to develop a new method for converting the local diameter distension waveform into a pressure waveform, through an exponential function whose parameters depend on the local wave speed. The proposed method was then tested at the common carotid artery. Diameter and blood velocity waveforms were acquired via ultrasound at the right common carotid artery while simultaneously recording pressure at the left common carotid artery via tonometer in 203 people (122 men, 50 ± 18 years). The wave speed was noninvasively estimated via the lnDU-loop method and then used to define the exponential function to convert the diameter into pressure. Noninvasive systolic and mean pressures estimated by the new technique were 3.8 ± 21.8 (p = 0.015) and 2.3 ± 9.6 mmHg (p = 0.011) higher than those obtained using tonometery. However, differences were much reduced and not significant in people >35 years (0.6 ± 18.7 and 0.8 ± 8.3 mmHg, respectively). This proof of concept study demonstrated that local wave speed, estimated from noninvasive local measurement of diameter and flow velocity, can be used to determine an exponential function that describes the relationship between local pressure and diameter. This pressure-diameter function can then be used for the noninvasive estimation of local arterial pressure.

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.

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.

Study Protocol: The Heart and Brain Study.

BACKGROUND: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart-brain association remain unclear. Recent evidence suggests that impairments in vascular phenotypes and cerebrovascular reactivity (CVR) may play an important role in cognitive decline. The Heart and Brain Study combines state-of-the-art vascular ultrasound, cerebrovascular magnetic resonance imaging (MRI) and cognitive testing in participants of the long-running Whitehall II Imaging cohort to examine these processes together. This paper describes the study protocol, data pre-processing and overarching objectives. METHODS AND DESIGN: The 775 participants of the Whitehall II Imaging cohort, aged 65 years or older in 2019, have received clinical and vascular risk assessments at 5-year-intervals since 1985, as well as a 3T brain MRI scan and neuropsychological tests between 2012 and 2016 (Whitehall II Wave MRI-1). Approximately 25% of this cohort are selected for the Heart and Brain Study, which involves a single testing session at the University of Oxford (Wave MRI-2). Between 2019 and 2023, participants will undergo ultrasound scans of the ascending aorta and common carotid arteries, measures of central and peripheral blood pressure, and 3T MRI scans to measure CVR in response to 5% carbon dioxide in air, vessel-selective cerebral blood flow (CBF), and cerebrovascular lesions. The structural and diffusion MRI scans and neuropsychological battery conducted at Wave MRI-1 will also be repeated. Using this extensive life-course data, the Heart and Brain Study will examine how 30-year trajectories of vascular risk throughout midlife (40-70 years) affect vascular phenotypes, cerebrovascular health, longitudinal brain atrophy and cognitive decline at older ages. DISCUSSION: The study will generate one of the most comprehensive datasets to examine the longitudinal determinants of the heart-brain association. It will evaluate novel physiological processes in order to describe the optimal window for managing vascular risk in order to delay cognitive decline. Ultimately, the Heart and Brain Study will inform strategies to identify at-risk individuals for targeted interventions to prevent or delay dementia.

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.