Patient-specific arterial wall generation for intracranial aneurysms with a variable and a near realistic vessel wall thickness for FSI studies.

BACKGROUND AND OBJECTIVE: Imaging methodologies such as, computed tomography (CT) aid in three-dimensional (3D) reconstruction of patient-specific aneurysms. The radiological data is useful in understanding their location, shape, size, and disease progression. However, there are serious impediments in discerning the blood vessel wall thickness due to limitations in the current imaging modalities. This further restricts the ability to perform high-fidelity fluid structure interaction (FSI) studies for an accurate assessment of rupture risk. FSI studies would require the arterial wall mesh to be generated to determine realistic maximum allowable wall stresses by performing coupled calculations for the hemodynamic forces with the arterial walls. METHODS: In the present study, a novel methodology is developed to geometrically model variable vessel wall thickness for the lumen isosurface extracted from CT scan slices of patient-specific aneurysms based on clinical and histopathological inputs. FSI simulations are carried out with the reconstructed models to assess the importance of near realistic wall thickness model on rupture risk predictions. RESULTS: During surgery, clinicians often observe translucent vessel walls, indicating the presence of thin regions. The need to generate variable vessel wall thickness model, that embodies the wall thickness gradation, is closer to such clinical observations. Hence, corresponding FSI simulations performed can improve clinical outcomes. Considerable differences in the magnitude of instantaneous wall shear stresses and von Mises stresses in the walls of the aneurysm was observed between a uniform wall thickness and a variable wall thickness model. CONCLUSION: In the present study, a variable vessel wall thickness generation algorithm is implemented. It was shown that, a realistic wall thickness modeling is necessary for an accurate prediction of the shear stresses on the wall as well as von Mises stresses in the wall. FSI simulations are performed to demonstrate the utility of variable wall thickness modeling.

Impact of hypertension and arterial wall expansion on transport properties and atherosclerosis progression.

This study explored the impact of hypertension on atheroma plaque formation through a mechanobiological model. The model incorporates blood flow via the Navier-Stokes equation. Plasma flow through the endothelium is determined by Darcy's law and the Kedem-Katchalsky equations, which consider the three-pore model utilized for substance flow across the endothelium. The behaviour of these substances within the arterial wall is described by convection-diffusion-reaction equations, while the arterial wall itself is modelled as a hyperelastic material using Yeoh's model. To accurately evaluate hypertension's influence, adjustments were made to incorporate wall compression-induced wall compaction by radial compression. This compaction impacts three key variables of the transport phenomena: diffusion, porosity, and permeability. Based on the obtained findings, we can conclude that hypertension significantly augments plaque growth, leading to an over 400% increase in plaque thickness. This effect persists regardless of whether wall mechanics are considered. Tortuosity, arterial wall permeability, and porosity have minimal impact on atheroma plaque growth under normal arterial pressure. However, the atheroma plaque growth changes dramatically in hypertensive cases. In such scenarios, the collective influence of all factors-tortuosity, permeability, and porosity-results in nearly a 20% increase in plaque growth. This emphasizes the importance of considering wall compression due to hypertension in patient studies, where elevated blood pressure and high cholesterol levels commonly coexist.

Estimation of the prevalence of isolated inter-scalene compression from simultaneous arterial and venous photoplethysmography in patients referred for suspected thoracic outlet syndrome.

Objective.In patients with suspected thoracic outlet syndrome (TOS), diagnosing inter-scalene compression could lead to minimally invasive treatments. During photo-plethysmography, completing a 30 s 90° abduction, external rotation ('surrender' position) by addition of a 15 s 90° antepulsion 'prayer' position, allows quantitative bilateral analysis of both arterial (A-PPG) and venous (V-PPG) results. We aimed at determining the proportion of isolated arterial compression with photo-plethysmography in TOS-suspected patients.Approach.We studied 116 subjects recruited over 4 months (43.3 ± 11.8 years old, 69% females). Fingertip A-PPG and forearm V-PPG were recorded on both sides at 125 Hz and 4 Hz respectively. A-PPG was converted to PPG amplitude and expressed as percentage of resting amplitude (% rest). V-PPG was expressed as percentage of the maximal value (% max) observed during the 'Surrender-Prayer' maneuver. Impairment of arterial inflow during the surrender (As+) or prayer (Ap+) phases were defined as a pulse-amplitude either <5% rest, or <25% rest. Incomplete venous emptying during the surrender (Vs+) or prayer (Vp+) phases were defined as V-PPG values either <70% max, or <87% max.Main results.Of the 16 possible associations of encodings, As - Vs - Ap - Vp- was the most frequent observation assumed to be a normal response. Isolated arterial inflow without venous outflow (As + Vs-) impairment in the surrender position was observed in 10.3% (95%CI: 6.7%-15.0%) to 15.1% (95%CI: 10.7%-20.4%) of limbs.Significance.Simultaneous A-PPG and V-PPG can discriminate arterial from venous compression and then potentially inter-scalene from other levels of compressions. As such, it opens new perspectives in evaluation and treatment of TOS.

Signals From Inflamed Perivascular Adipose Tissue Contribute to Small-Vessel Dysfunction in Women With Human Immunodeficiency Virus.

BACKGROUND: People with the human immunodeficiency virus (PWH) have microvascular disease. Because perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels. METHODS: Subcutaneous small arteries were dissected with or without PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged < 50 years and 10 matched women without HIV, and studied on isometric myographs. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. Adipokines and markers of inflammation and ROS were assayed in PVAT. RESULTS: PVAT surrounding the small arteries in control women significantly (P < .05) enhanced acetylcholine-induced endothelium-dependent relaxation and NO, and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < .05) in WWH whose PVAT released less adiponectin but more markers of ROS and inflammation. Moderation of contractions by PVAT were correlated positively with adipose adiponectin. CONCLUSIONS: PVAT from WWH has oxidative stress, inflammation, and reduced release of adiponectin, which may contribute to enhanced contractions and therefore could promote small-artery dysfunction.

The use of venous blood gas in assessing arterial acid-base and oxygenation status - an analysis of aggregated data from multiple studies evaluating the venous to arterial conversion (v-TAC) method.

BACKGROUND: Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria. RESEARCH DESIGN AND METHODS: We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO2, and PO2. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits. RESULTS: 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (-0.029 to 0.031), PCO2 -0.08 (-0.65 to 0.49) kPa, and PO2 0.04 (-1.71 to 1.78) kPa, with similar values for all sub-group analyses. CONCLUSION: These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid-base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.

Exploring the Therapeutic Potential of C-Type Natriuretic Peptide for Preeclampsia.

BACKGROUND: Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models. METHODS: Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling. RESULTS: CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction. CONCLUSIONS: Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.

Sex Modifies the Effect of COVID-19 on Arterial Elasticity.

There is limited long-term evidence on the effects of COVID-19 on vascular injury between male and female sex. An adult cohort of COVID-19 survivors (COVID+) and confirmed SARS-CoV-2 antibody-negative participants (COVID-) were prospectively enrolled. COVID+ participants who have documented the presence of persistent symptoms four weeks following infection were considered to have post-acute sequelae of COVID-19 (PASC). Non-invasive, FDA-approved EndoPAT (Endo-PAT2000) was used for endothelial assessment. COVID-(n = 94) were 1:1 propensity score matched to COVID+ (n = 151) on baseline covariates including sex. Among COVID+, 66.2% (n = 100) had PASC. Higher levels of coagulation marker, D-dimer (p = 0.001), and gut permeability marker, zonulin (p = 0.001), were associated with female sex. Estimated differences in augmentation index (AI) between COVID- (0.9 ± 17.2) and COVID+ (8.4 ± 15.7; p = 0.001) and between female and male sex (12.9 ± 1.9; p < .0001) were observed. Among COVID+ with PASC, the average AI (10.5 ± 1.6) was 9.7 units higher than COVID- (p < .0001) and 6.2 units higher compared to COVID+ with no PASC (p = 0.03). COVID+ PASC+ female sex had the highest AI (14.3 ± 1.9). The effects of SARS-CoV-2 infection on vascular function varies across strata of sex and female sex in the post-acute phase of COVID-19 have the worse arterial elasticity (highest AI).

The bottlenose dolphin (Tursiops truncatus): a novel model for studying healthy arterial aging.

Endothelial function declines with aging and independently predicts future cardiovascular disease (CVD) events. Diving also impairs endothelial function in humans. Yet, dolphins, being long-lived mammals adapted to diving, undergo repetitive cycles of tissue hypoxia-reoxygenation and disturbed shear stress without manifesting any apparent detrimental effects, as CVD is essentially nonexistent in these animals. Thus, dolphins may be a unique model of healthy arterial aging and may provide insights into strategies for clinical medicine. Emerging evidence shows that the circulating milieu (bioactive factors in the blood) is at least partially responsible for transducing reductions in age-related endothelial function. To assess whether dolphins have preserved endothelial function with aging because of a protected circulating milieu, we tested if the serum (pool of the circulating milieu) of bottlenose dolphins (Tursiops truncatus) induces the same arterial aging phenotype as the serum of age-equivalent humans. We incubated conduit arteries from young and old mice with dolphin and human serum and measured endothelial function ex vivo via endothelium-dependent dilation to acetylcholine. Although young arteries incubated with serum from midlife/older adult human serum had lower endothelial function, those incubated with dolphin serum consistently maintained high endothelial function regardless of the age of the donor. Thus, studying the arterial health of dolphins could lead to potential novel therapeutic strategies to improve age-related endothelial dysfunction in humans.NEW & NOTEWORTHY We demonstrate that, unlike serum of midlife/older adult humans, age-matched dolphin serum elicits higher endothelial function ex vivo in young mouse carotid arteries, suggesting that the circulating milieu of bottlenose dolphins may be geroprotective. We propose that dolphins are a novel model to investigate potential novel therapeutic strategies to mitigate age-related endothelial dysfunction in humans.

The resistive and pulsatility indices of the dorsal metatarsal artery for the screening of peripheral lower artery disease in patients with and without diabetes.

BACKGROUND: In lower extremity peripheral artery disease (PAD), the ankle-brachial index (ABI) is an easily reproducible diagnostic tool for PAD, but it loses reliability when > 1.4 due to calcification of the vessel wall. Patients with diabetes are at higher risk for wall calcification. In order to overcome the limitation and reliability of ABI, particularly in patients with diabetes, we decided to assess resistive (RI) and pulsatility index (PI) by ultrasound doppler of the dorsal metatarsal artery (DMA). RESULTS: We therefore analyzed 51 legs (32 patients), evaluating the correlation between PI, RI, and ABI. Patients with diabetes were 21 (65.6 %), accounting for 33 legs (64.7 %). Out of 51 legs assessed, 37 (72.5 %) cases had compressible arteries, whereas in 14 legs (27.5 %) ABI was not calculable due to wall calcification. PAD was significantly associated with lower both RI and PI of the DMA (both p < 0.000). RI, but not PI, showed a significant correlation (r = 0.535) with ABI, when ABI was less than 1.4, but not when ABI > 1.4. When analyzed separately, patients with diabetes showed a similar figure in comparison with those without diabetes (r = 0.600), RI, but not PI, showed a significant correlation with ABI. CONCLUSION: Dorsal metatarsal artery resistive index (MARI) showed a significant inverse correlation with PAD, similarly to ABI, irrespective of the presence of diabetes. MARI seems to be an effective screening tool for PAD even in patients with wall calcification. Further studies are needed for confirming the results of the present pilot study.

Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

Acute partial sleep restriction does not impact arterial function in young and healthy humans.

Habitual short sleep durations are associated with several cardiovascular diseases. Experimental research generally supports these findings as metrics of arterial function are impaired after complete deprivation of sleep and after longer periods of partial sleep restriction. The acute influence of a single instance of partial sleep restriction (PSR), however, has not been defined. We evaluated arterial structure and function among 32 university-aged participants on two occasions: once after normal habitual sleep (NS), and again the morning after an acute partial sleep restriction (PSR) intervention involving only 3 h of sleep for a single night. Endothelial function was measured using ultrasonography at the brachial artery via flow-mediated dilatation (FMD), and a ramp peak oxygen uptake test was used to evaluate cardiorespiratory fitness. Blood samples were collected from a subset of participants to investigate the influence of circulatory factors on cellular mechanisms implicated in endothelial function. Sleep duration was lower after a night of PSR compared to NS (P < 0.001); however, there were no appreciable differences in any haemodynamic outcome between conditions. FMD was not different between NS and PSR (NS: 6.5 ± 2.9%; PSR: 6.3 ± 2.9%; P = 0.668), and cardiorespiratory fitness did not moderate the haemodynamic response to PSR (all P > 0.05). Ex vivo cell culture results aligned with in vivo data, showing that acute PSR does not alter intracellular processes involved in endothelial function. No differences in arterial structure or function were observed between NS and acute PSR in healthy and young participants, and cardiorespiratory fitness does not modulate the arterial response to acute sleep restriction.

A meta-analysis: elucidating diagnostic thresholds of peak systolic flow velocities in thyroid arteries for the discrimination of Graves' disease and destructive thyrotoxicosis.

Objective: This meta-analysis examines peak systolic velocities (PSVs) in thyroid arteries as potential biomarkers for thyroid disorders, which includes treated and untreated Graves' disease(GD) and destructive thyrotoxicosis(DT). Methods: A search across databases including PubMed, Google Scholar, Embase, and Web of Science identified studies assessing peak systolic flow velocity in the inferior thyroid artery (ITA-PSV) and superior thyroid artery (STA-PSV) diagnostic efficacy in GD and DT.And the search was restricted to publications in the English language.The analysis compared STA-PSV and ITA-PSV across patient groups, evaluating intra-group variances and synthesizing sensitivity and specificity data. Results: The analysis covered 18 studies with 1276 GD, 564 DT patients, and 544 controls. The difference of STA-PSV between GD group, DT group and normal group and the difference of ITA-PSV were analyzed in subgroups, and there was no statistical significance between subgroups when comparing any two groups. Normal subjects displayed intra-group ITA-PSV and STA-PSV differences with established cut-off values of 20.33 cm/s (95% CI, 17.48-23.18) for ITA-PSV and 25.61 cm/s (95% CI, 20.37-30.85) for STA-PSV. However, no significant intra-group differences were observed in the STA-PSV and ITA-PSV cut-off values among groups with GD or DT. The combined cut-off values for these patient groups and normal subjects were 68.63 cm/s (95% CI, 59.12-78.13), 32.08 cm/s (95% CI, 25.90-38.27), and 23.18 cm/s (95% CI, 20.09-26.28), respectively. The diagnostic odds ratio(DOR) for these values was 35.86 (95% CI, 18.21-70.60), and the area under the summary receiver operating characteristic (SROC) curve was 0.91, with a sensitivity estimate of 0.842 (95% CI, 0.772-0.866). Conclusion: PSVs in thyroid arteries are useful diagnostic tools in distinguishing DT from GD. A PSV above 68.63 cm/s significantly improves GD diagnosis with up to 91% efficacy. No notable differences were found between superior and inferior thyroid arteries in these conditions.

Socioeconomic status as a potential mediator of arterial aging in marginalized ethnic and racial groups: current understandings and future directions.

Cardiovascular diseases (CVDs) are the leading cause of death in the United States. However, disparities in CVD-related morbidity and mortality exist as marginalized racial and ethnic groups are generally at higher risk for CVDs (Black Americans, Indigenous People, South and Southeast Asians, Native Hawaiians, and Pacific Islanders) and/or development of traditional CVD risk factors (groups above plus Hispanics/Latinos) relative to non-Hispanic Whites (NHW). In this comprehensive review, we outline emerging evidence suggesting these groups experience accelerated arterial dysfunction, including vascular endothelial dysfunction and large elastic artery stiffening, a nontraditional CVD risk factor that may predict risk of CVDs in these groups with advancing age. Adverse exposures to social determinants of health (SDOH), specifically lower socioeconomic status (SES), are exacerbated in most of these groups (except South Asians-higher SES) and may be a potential mediator of accelerated arterial aging. SES negatively influences the ability of marginalized racial and ethnic groups to meet aerobic exercise guidelines, the first-line strategy to improve arterial function, due to increased barriers, such as time and financial constraints, lack of motivation, facility access, and health education, to performing conventional aerobic exercise. Thus, identifying alternative interventions to conventional aerobic exercise that 1) overcome these common barriers and 2) target the biological mechanisms of aging to improve arterial function may be an effective, alternative method to aerobic exercise to ameliorate accelerated arterial aging and reduce CVD risk. Importantly, dedicated efforts are needed to assess these strategies in randomized-controlled clinical trials in these marginalized racial and ethnic groups.

Flexural pulse wave velocity in blood vessels.

Arteriosclerosis is a major risk factor for cardiovascular disease and results in arterial vessel stiffening. Velocity estimation of the pulse wave sent by the heart and propagating into the arteries is a widely accepted biomarker. This symmetrical pulse wave propagates at a speed which is related to the Young's modulus through the Moens Korteweg (MK) equation. Recently, an antisymmetric flexural wave has been observed in vivo. Unlike the symmetrical wave, it is highly dispersive. This property offers promising applications for monitoring arterial stiffness and early detection of atheromatous plaque. However, as far as it is known, no equivalent of the MK equation exists for flexural pulse waves. To bridge this gap, a beam based theory was developed, and approximate analytical solutions were reached. An experiment in soft polymer artery phantoms was built to observe the dispersion of flexural waves. A good agreement was found between the analytical expression derived from beam theory and experiments. Moreover, numerical simulations validated wave speed dependence on the elastic and geometric parameters at low frequencies. Clinical applications, such as arterial age estimation and arterial pressure measurement, are foreseen.

In the Loop: Endovascular Pedal Arch Revascularization.

Advanced endovascular techniques are increasingly being utilized to treat patients with peripheral arterial disease and chronic limb-threatening ischemia to improve lower extremity arterial perfusion. In diabetic patients, pedal arch patency has been associated with improved wound healing, limb salvage, and overall survival. Pedal-plantar loop revascularization is a technique that can restore arterial inflow between the dorsal and plantar arteries of the foot. This article will describe the inframallelolar arterial anatomy and focus on imaging, percutaneous endovascular techniques, and clinical study outcomes of pedal artery interventions.