Vascular Compliance Research Articles

Benefits of Curcumin in the Vasculature: A Therapeutic Candidate for Vascular Remodeling in Arterial Hypertension and Pulmonary Arterial Hypertension?

Growing evidence suggests that hypertension is one of the leading causes of cardiovascular morbidity and mortality since uncontrolled high blood pressure increases the risk of myocardial infarction, aortic dissection, hemorrhagic stroke, and chronic kidney disease. Impaired vascular homeostasis plays a critical role in the development of hypertension-induced vascular remodeling. Abnormal behaviors of vascular cells are not only a pathological hallmark of hypertensive vascular remodeling, but also an important pathological basis for maintaining reduced vascular compliance in hypertension. Targeting vascular remodeling represents a novel therapeutic approach in hypertension and its cardiovascular complications. Phytochemicals are emerging as candidates with therapeutic effects on numerous pathologies, including hypertension. An increasing number of studies have found that curcumin, a polyphenolic compound derived from dietary spice turmeric, holds a broad spectrum of pharmacological actions, such as antiplatelet, anticancer, anti-inflammatory, antioxidant, and antiangiogenic effects. Curcumin has been shown to prevent or treat vascular remodeling in hypertensive rodents by modulating various signaling pathways. In the present review, we attempt to focus on the current findings and molecular mechanisms of curcumin in the treatment of hypertensive vascular remodeling. In particular, adverse and inconsistent effects of curcumin, as well as some favorable pharmacokinetics or pharmacodynamics profiles in arterial hypertension will be discussed. Moreover, the recent progress in the preparation of nano-curcumins and their therapeutic potential in hypertension will be briefly recapped. The future research directions and challenges of curcumin in hypertension-related vascular remodeling are also proposed. It is foreseeable that curcumin is likely to be a therapeutic agent for hypertension and vascular remodeling going forwards.

Forest Bathing Is Better than Walking in Urban Park: Comparison of Cardiac and Vascular Function between Urban and Forest Parks.

Forest bathing is beneficial for human health. To investigate whether walking in forest or urban parks affects cardiovascular functions (CVFs), the present study was conducted in five forest trails in the Xitou Experimental Forest and in five urban parks in Taipei city. We recruited 25 adult volunteers for an observational pilot study in forest parks (n = 14) and urban parks (n = 11). CVFs were assessed by measuring the arterial pressure waveform using an oscillometric blood pressure (BP) device. The baseline and paired differences of systolic BP (SBP), central end SBP, heart rate, left ventricle (LV) dP/dt max and cardiac output in participants were lower before and after walking in a forest park than those in an urban park. In addition, the systemic vascular compliance and brachial artery compliance of those who walked in a forest park were significantly higher compared with those in an urban park. Linear mixed models demonstrated lower levels of SBP by 5.22 mmHg, heart rate by 2.46 beats/min, and cardiac output by 0.52 L/min, and LV dP/dt max by 146.91 mmHg/s among those who walked in forest compared to those in an urban park after controlling covariates. This study provides evidence of the potential beneficial effects of walking exercise in forest parks on CVFs.

Acute Cardiovascular Effects of Hydrotreated Vegetable Oil Exhaust.

Ambient air pollution is recognized as a key risk factor for cardiovascular morbidity and mortality contributing to the global disease burden. The use of renewable diesel fuels, such as hydrotreated vegetable oil (HVO), have increased in recent years and its impact on human health are not completely known. The present study investigated changes in cardiovascular tone in response to exposure to diluted HVO exhaust. The study participants, 19 healthy volunteers, were exposed in a chamber on four separate occasions for 3 h and in a randomized order to: (1) HVO exhaust from a wheel loader without exhaust aftertreatment, (2) HVO exhaust from a wheel loader with an aftertreatment system, (3) clean air enriched with dry NaCl salt particles, and (4) clean air. Synchronized electrocardiogram (ECG) and photoplethysmogram (PPG) signals were recorded throughout the exposure sessions. Pulse decomposition analysis (PDA) was applied to characterize PPG pulse morphology, and heart rate variability (HRV) indexes as well as pulse transit time (PTT) indexes were computed. Relative changes of PDA features, HRV features and PTT features at 1, 2, and 3 h after onset of the exposure was obtained for each participant and exposure session. The PDA index A13, reflecting vascular compliance, increased significantly in both HVO exposure sessions but not in the clean air or NaCl exposure sessions. However, the individual variation was large and the differences between exposure sessions were not statistically significant.

Semiautomated Software to Improve Stability and Reduce Operator-Induced Variation in Vascular Ultrasound Speckle Tracking.

Ultrasound is useful in predicting arteriovenous fistula (AVF) maturation, which is essential for hemodialysis in end-stage renal disease patients. We developed ultrasound software that measures circumferential vessel wall strain (distensibility) using conventional ultrasound Digital Imaging and Communications in Medicine (DICOM) data. We evaluated user-induced variability in measurement of arterial wall distensibility and upon finding considerable variation we developed and tested 2 methods for semiautomated measurement. Ultrasound scanning of arteries of 10 subjects scheduled for AVF surgery were performed. The top and bottom of the vessel wall were tracked using the Kanade-Lucas-Tomasi (KLT) feature-tracking algorithm over the stack of images in the DICOM cine loops. The wall distensibility was calculated from the change of vessel diameter over time. Two semiautomated methods were used for comparison. The location of points selected by users for the cine loops varied significantly, with a maximum spread of up to 120 pixels (7.8 mm) for the top and up to 140 pixels (9.1 mm) for the bottom of the vessel wall. This variation in users' point selection contributed to the variation in distensibility measurements (ranging from 5.63 to 41.04%). Both semiautomated methods substantially reduced variation and were highly correlated with the median distensibility values obtained by the 10 users. Minimizing user-induced variation by standardizing point selection will increase reproducibility and reliability of distensibility measurements. Our recent semiautomated software may help expand use in clinical studies to better understand the role of vascular wall compliance in predicting the maturation of fistulas.

Pulmonary vascular resistance and compliance in pulmonary blood flow alterations in children with congenital heart disease.

There is a unique hyperbolic relationship between pulmonary vascular resistance (Rp) and compliance (Cp); however, the characteristics of this coupling curve in pulmonary blood flow alterations remains unknown in children with congenital heart disease. We aimed to explore the Rp-Cp coupling and resistant-compliance (RC) time among them. We retrospectively reviewed catheterization data and calculated Rp and Cp in 217 subjects with ventricular septal defect. Median age and weight at catheterization were 2.8 (1.7-4.4) months and 4.3 (3.7-5.3) kg, respectively. Pulmonary hemodynamic parameters were as follows: mean pulmonary arterial pressure: 36 (28-43) mmHg; the amount of pulmonary blood flow (Qp): 14.2 (11.6-17.6) L/min/m2; Rp: 1.95 (1.38-2.59) Wood unit m2; Cp: 2.98 (2.42-3.88) mmHg/mL/m2; and RC time: 0.35 (0.30-0.40) s. RC time remained unchanged according to alterations in Qp (P = 0.206); however, the relationship between logarithm transformations of Rp and Cp showed more steeper according to an increase in Qp. The pulmonary circulation depends upon Cp rather than Rp according to the degree of Qp despite the constancy in RC time. We should take both Rp and Cp into consideration when evaluating the pulmonary circulation among children with congenital heart disease.

Pulsatility damping in the microcirculation: Basic pattern and modulating factors.

Blood flow pulsatility is an important determinant of macro- and microvascular physiology. Pulsatility is damped largely in the microcirculation, but the characteristics of this damping and the factors that regulate it have not been fully elucidated yet. Applying computational approaches to real microvascular network geometry, we examined the pattern of pulsatility damping and the role of potential damping factors, including pulse frequency, vascular viscous resistance, vascular compliance, viscoelastic behavior of the vessel wall, and wave propagation and reflection. To this end, three full rat mesenteric vascular networks were reconstructed from intravital microscopic recordings, a one-dimensional (1D) model was used to reproduce pulsatile properties within the network, and potential damping factors were examined by sensitivity analysis. Results demonstrate that blood flow pulsatility is predominantly damped at the arteriolar side and remains at a low level at the venular side. Damping was sensitive to pulse frequency, vascular viscous resistance and vascular compliance, whereas viscoelasticity of the vessel wall or wave propagation and reflection contributed little to pulsatility damping. The present results contribute to our understanding of mechanical forces and their regulation in the microcirculation.

Superior Fitting of Arterial Resistance and Compliance Parameters With Genetic Algorithms in Models of Dynamic Cerebral Autoregulation.

The capacity of discriminating between normal and impaired dynamic cerebral autoregulation (dCA), based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF), has considerable clinical relevance. This study aimed to quantify the separate contributions of vascular resistance and compliance as parameters that could reflect myogenic and metabolic mechanisms to dCA. Forty-five subjects were studied under normo and hypercapnic conditions induced by breathing a mixture of 5% carbon dioxide in air. Dynamic cerebrovascular resistance and compliance models with ABP as input and CBFV as output were fitted using Genetic Algorithms to identify parameter values for each subject, and respiratory condition. The efficiency of dCA was assessed from the model's generated CBFV response to an ABP step change, corresponding to an autoregulation index of 5.56 ± 1.57 in normocapnia and 2.38 ± 1.73 in hypercapnia, with an area under the ROC curve (AUC) of 0.9 between both conditions. Vascular compliance increased from 0.75 ± 0.7 ml/mmHg in normocapnia to 5.82 ± 12.0 ml/mmHg during hypercapnia, with an AUC of 0.88. Further work is needed to validate this approach in clinical applications where individualised model parameters could provide relevant diagnostic and prognostic information about dCA impairment.

Increased Right Ventricular Pressure as a Predictor of Acute Decompensated Heart Failure in End-Stage Renal Disease Patients on Maintenance Hemodialysis.

Background and ObjectivesMany patients with end-stage renal disease (ESRD) on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). This study aimed to determine the factors associated with acute decompensation events among ESRD patients undergoing HD.MethodsWe retrospectively investigated ESRD patients on HD using a medical record review. We divided the patients into those admitted to hospital due to acute decompensated heart failure (ADHF) and those who were not. We compared the medical histories, electrocardiograms, and echocardiographic and laboratory data between the two groups.ResultsOf the 188 ESRD patients on HD, 87 were excluded, and 101 were enrolled (mean age: 63.7 years; 52.1% male). Thirty patients (29.7%) were admitted due to ADHF. These patients exhibited similar left ventricular ejection fraction (LVEF), left ventricular (LV) mass index, and E/E′ values compared to the non-ADHF group. However, the ADHF group exhibited significantly higher tricuspid regurgitation (TR) jet velocity (2.9±0.6 vs. 2.5±0.4 m/s; p=0.004) and right ventricular systolic pressure (RVSP) (43.5±17.2 vs. 34.2±9.9 mmHg; p=0.009) than the non-ADHF group, respectively. A multivariate logistic regression analysis demonstrated that the TR jet velocity (odds ratio, 8.356; 95% confidence interval, 1.806–38.658; p=0.007) was an independent predictor of ADHF after adjusting for age and sex, while the LVEF and E/E′ were not.ConclusionsOur data showed that an increased TR jet velocity was an independent predictor of ADHF events in ESRD patients on HD, but the LVEF and E/E′ were not.

678 Safety and clinical role of the exercise testing during pregnancy

Abstract Aims The prevalence of arterial hypertension (AH) during pregnancy is ranging from 2% to 10%. Diagnostic criteria are based on rest blood pressure measurements. Exercise testing (ET) is a useful approach to detect latent hypertensive condition and may allow early diagnosis. Despite physical activity is encouraged during pregnancy in order to prevent systemic disorders, ET is not commonly performed during pregnancy due to limited data of safety. The aim of the study is to test the safety of ET during pregnancy and to explore its role in predicting the development of AH. Methods Pregnant women were tested through submaximal ET at Dyspnoea Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milano. The exercise was performed on a stationary cycle on which the power was increased of 15 W every 2 min starting from 5 W (first step). Subjects were continuously monitored during exercise through EKG, non-invasive blood pressure measurements every 2 min and peripheral oxygen saturation. 3 months clinical follow-up was made in order to assess the presence of AH or other pregnancy disorders. U-test analysis was performed in order to verify statistical difference between hypertensive and non-hypertensive women. Heart rate, systolic and diastolic blood pressure (SBP and DBP) were measured at rest, at the first step and at peak of ET and have been considered in analysis. U-test (Mann–Whitney analysis) was adopted to test difference between hypertensive and non-hypertensive group. Women were followed-up at second trimester (22nd–25th week of pregnancy) in order to monitor the clinical condition, the development of AH or any gestational disorders (e.g. diabetes and pre-eclampsia). Results All 73 women (mean age 32 years, gestational age 12–14 weeks) consecutively enrolled have completed the ET. The mean maximum load achieved was 65 W, no abrupt interruption of ET was needed because of symptoms or intolerance. Mean HR at rest, at the first step and at the peak was 80 b.p.m., 91 b.p.m. and 128 b.p.m., respectively. Mean arterial pressure reached values of 97/62 mmHg at rest, 107/66 mmHg at the first step and 140/73 mmHg at peak exercise. At follow-up 9 of 73 showed clinical disorders (12%) of which 5 patients had hypertension (6.8%), 3 patients had diabetes (4.1%) and 1 had pre-eclampsia (1.4%). Comparing the group with AH (n 5) with the group without AH (n 68), SBP at the first step (median values 127 mmHg vs 104 mmHg, P = 0.009), the DBP at rest (median values 72 mmHg vs 60 mmHg, P = 0.039) and the DBP at the peak (median values 90 mmHg vs 69.5 mmHg, P = 0.038) were significantly higher in the group with AH. Among these parameters a logistic regression selected the SBP as best predictor for developing AH (OR 1.139, 95% IC 029–1.261, P = 0.012). Conclusions Our results showed that submaximal ET is safe in pregnancy. Although limited, our data seem to support the validity of ET, even submaximal, in order to stratify the risk of developing AH in pregnancy. Moreover, even SBP response at first step could be considered in a normal and expected range, we can speculate that a relatively excessive increase of BP in the early phase of exercise could reflect a pre-clinical impairment of vascular compliance predisposing AH during the second gestational trimester. Further data are needed to validate our results.

Lower regional cerebrovascular reactivity relates to worse episodic memory among older adults

AbstractBackgroundCerebrovascular reactivity (CVR) measures the ability of the cerebrovasculature to respond to vasoactive stimuli. Decreased CVR in the default mode network (DMN) has been associated with increased vascular risk factor burden. DMN connectivity is fundamentally dependent on vascular compliance, which can be altered in MCI, and may impact episodic memory consolidation. This study cross‐sectionally evaluated whether the topography of CVR is associated with episodic memory performance.MethodVanderbilt Memory & Aging Project participants free of stroke were included (n=117, 76.0±7.3 years, 46% female). Participants underwent neuropsychological assessment and multimodal 3T brain MRI, including T1‐weighted imaging and T2*‐weighted blood‐oxygenation level‐dependent (BOLD‐fMRI) for quantifying CVR. During the BOLD‐fMRI acquisition, a hypercapnic normoxic respiratory challenge was administered by alternating normocapnic normoxia and hypercapnic normoxia (5% CO2/95%‐air) in 90s blocks. BOLD‐fMRI data were time‐delay processed, yielding whole‐brain mapping of the maximum correlation with the gas stimulus (CVRMAX) and time‐to‐max CVR (CVRDELAY). Mean CVR metrics were calculated in atlas‐derived DMN regions. Ordinary least squares regression models related DMN‐CVR to episodic memory performance adjusting for demographics, Framingham Stroke Risk Profile, and apolipoprotein E‐e4 status. Clusters were corrected using family‐wise‐error rate p<0.05.ResultDMN‐CVRMAX was related to episodic memory performance (b=1.0x10‐3, p=0.03) but DMN‐CVRDELAY was not (p=0.09). In voxelwise analysis relating CVRMAX to memory, seven clusters surviving correction were identified, all suggesting lower CVRMAX related to worse memory performance. The peak value of the top cluster was located in the middle temporal gyrus. In voxelwise analysis relating CVRDELAY to memory, 11 clusters surviving correction were identified, all indicating longer CVRDELAY related to worse memory performance. The peak value of the top cluster was located in postcentral gyrus.ConclusionAmong older adults, lower DMN‐CVRMAX is associated with worse episodic memory performance and this association is not confined to the DMN. Associations between regionally reduced vascular compliance and episodic memory may result from vascular impairment of large‐scale brain networks such as the DMN, though these associations should be further explored. T32‐AG058524, IIRG‐08‐88733, R01‐AG034962, R01‐NS100980, K24‐AG046373, P20‐AG068082

Effects of Power Walking on Body Composition and Vascular Compliance in Inactive, Smoking, and Obese Middle-aged Women

본 연구는 파워 워킹이 비활동적이면서 흡연을 하는 비만 중년여성을 대상으로 신체조성과 혈관 탄성에 미치는 영향을 규명 하는데 있다. 대상자들은 D 광역시 콜 센터에 근무하는 자들로 흡연을 시작한 지 6년 이상이었고, 규칙적인 스포츠활동에 참여하지 않았으며, 비만 이외에 어떠한 질환도 없었다. 실험 목적과 절차를 충분히 설명한 후 자발적으로 참여 의사를 밝히 18명을 대상으로 파워 워킹 운동프로그램을 적용하였다. 개인별 운동강도는 폴라 측정기를 이용하여 컨트롤 하였으며, 1-3주 50%HRmax, 4-6주 60%HRmax로 설정하여 다음과 같은 결과를 얻었다. 첫째, 신체조성의 변화는 파워 워킹 참여 후 체중, 체지방율, BMI에서 유의한 감소를 보였다(p<.05). 둘째, 혈관 탄성의 변화는 파워 워킹 참여 후 오른손, 왼손, 오른발, 왼발에서 유의한 증가를 보였다(p<.05) 따라서 비활동적이면서 흡연을 하는 비만 중년여성에게 규칙적인 파워 워킹은 체중과 체지방을 감소시키고, 혈관 기능을 개선 시켜 건강한 일상생활을 하는데 필수적인 운동요법이라고 할 수 있다.This study aims to examine the effects of power walking on body composition and vascular compliance in inactive, smoking, and obese middle-aged women. At the time of this study, the subjects were working for a call center in D metropolitan city, had been smoking for six years or more, were not participating in regular sports activities, and had no diseases besides obesity. After fully explaining the experimental purpose and procedure, a power walking exercise program was conducted with 18 total subjects who voluntarily agreed to participate in the program. The individual exercise intensity was controlled by using a polar measuring instrument. Applying 50% HRmax for 1-3 weeks and 60% HRmax for 4-6 weeks, the results were obtained as follows. First, regarding the change in body composition, there were significant decrease in weight, body fat percentage, and BMI after participating in the power walking (p<.05). Second, regarding the change in vascular compliance, there were significant increase in the right hand, left hand, right foot, and left foot after participating in the program (p<.05). Such results imply that regular power walking may be an essential exercise therapy for healthy daily life by reducing both weight and body fat percentage, as well as improving vascular function in inactive, smoking, and obese middle-aged women.

Patient-Specific Computational Analysis of Hemodynamics in Adult Pulmonary Hypertension.

Pulmonary hypertension (PH) is a progressive disease characterized by elevated pressure and vascular resistance in the pulmonary arteries. Nearly 250,000 hospitalizations occur annually in the US with PH as the primary or secondary condition. A definitive diagnosis of PH requires right heart catheterization (RHC) in addition to a chest computed tomography, a walking test, and others. While RHC is the gold standard for diagnosing PH, it is invasive and posseses inherent risks and contraindications. In this work, we characterized the patient-specific pulmonary hemodynamics in silico for diverse PH WHO groups. We grouped patients on the basis of mean pulmonary arterial pressure (mPAP) into three disease severity groups: at-risk ([Formula: see text], denoted with A), mild ([Formula: see text], denoted with M), and severe ([Formula: see text], denoted with S). The pulsatile flow hemodynamics was simulated by evaluating the three-dimensional Navier-Stokes system of equations using a flow solver developed by customizing OpenFOAM libraries (v5.0, The OpenFOAM Foundation). Quasi patient-specific boundary conditions were implemented using a Womersley inlet velocity profile and transient resistance outflow conditions. Hemodynamic indices such as spatially averaged wall shear stress ([Formula: see text]), wall shear stress gradient ([Formula: see text]), time-averaged wall shear stress ([Formula: see text]), oscillatory shear index ([Formula: see text]), and relative residence time ([Formula: see text]), were evaluated along with the clinical metrics pulmonary vascular resistance ([Formula: see text]), stroke volume ([Formula: see text]) and compliance ([Formula: see text]), to assess possible spatiotemporal correlations. We observed statistically significant decreases in [Formula: see text], [Formula: see text], and [Formula: see text], and increases in [Formula: see text] and [Formula: see text] with disease severity. [Formula: see text] was moderately correlated with [Formula: see text] and [Formula: see text] at the mid-notch stage of the cardiac cycle when these indices were computed using the global pulmonary arterial geometry. These results are promising in the context of a long-term goal of identifying computational biomarkers that can serve as surrogates for invasive diagnostic protocols of PH.

Differential biomechanics in resistance arteries of male compared with female Dahl hypertensive rats.

Background:Increase in vascular stiffness is associated with a higher risk of cardiovascular morbidity and mortality and is likely sex-specific.Method:Our objectives were to compare structural and functional alterations in small resistance arteries as related to vascular stiffness from Dahl salt-sensitive male and female rats (n = 8, mean ± s.e.m.).Results:Arterial blood pressure and pulse wave velocity were significantly (P < 0.05) elevated in males (161 ± 3 mmHg; 6.4 ± 0.2 m/s) and females (147 ± 2 mmHg; 5.5 ± 0.1 m/s) on a high (H) salt compared with regular (R) diets but were significantly higher in males (H) than in all others. Significant increases in collagen and smooth muscle cell areas were evident in ultrastructure of mesenteric arteries of hypertensive males compared to normotensive or corresponding females. There were no significant differences in composite Young's modulus (CYM) between groups. Vasoconstriction resulted in significantly higher CYM in male (H: 8.6 ± 1 KPa) than R (4.5 ± 0.8 KPa), and the corresponding females (H: 5.6 ± 0.6 KPa and R: 5 ± 0.9 KPa). In contrast, vasodilation significantly reduced CYM in the male groups (H: 2.5 ± 0.4 KPa and R: 2.7 ± 0.5 KPa) compared with the corresponding values in females (H: 4.2 ± 0.6 KPa and R: 5 ± 0.5 KPa). Moreover, the slope of pressure-volume curves revealed significantly greater distended vascular compliance in male H than R, and the corresponding females.Conclusion:Our findings are supportive of a link between high salt intake and elevated blood pressure as being sex specific, likely involving sex-dependent changes in ultrastructure of the vessels, which ultimately may alter the biomechanics, and thus, the haemodynamic functions of both macro-circulation and micro-circulations.

Degree of change in right ventricular adaptation measures during axillary Impella support informs risk stratification for early, severe right heart failure following durable LVAD implantation

Risk assessment for early, severe right heart failure (RHF) after LVAD implantation remains imperfect. We sought to define the differences in RV adaptation and load after axillary Impella support between patients who experienced RHF and those who did not. Seventeen of 18 patients included were deemed intermediate or high risk for RHF by EUROMACS-RHF score. Before Impella insertion, RV adaptation parameters (RAP, RAP:PCWP, PAPi) were worse in the non-RHF group compared to the RHF group. In both groups, RV load parameters (effective pulmonary arterial elastance, pulmonary vascular resistance, and pulmonary vascular compliance) improved after Impella insertion. Lesser improvements in RV adaptation were seen in the RHF group. Moreover, load-to-adaptation relationships (EA/RAP and EA/RAP:PCWP) worsened to a greater degree. In patients at intermediate or high risk for RHF after LVAD, assessment of RV adaptation and load during axillary Impella support may improve risk stratification.

Pulmonary vascular resistance and compliance in individuals with trisomy 18.

Individuals with trisomy 18 (T18) usually have congenital heart disease, often with pulmonary hypertension, which is associated with poor outcomes. This study aimed to explore the characteristics of pulmonary circulation including pulmonary vascular resistance (Rp) and compliance (Cp) among them. We retrospectively reviewed cardiac catheterization data in subjects with T18, trisomy 21 (T21), and without chromosomal anomaly (control group) who were referred due to heart failure associated with ventricular septal defect between 2000 and 2020. Pulmonary hemodynamic parameters including Rp and Cp were compared between these groups. We studied 20 subjects with T18, 88 subjects with T21, and 240 control subjects. There was no significant difference in age (T18: 4.6 [3.0-6. 9] vs. T21: 2.8 [1.9-4.0] vs. control: 2.9 [1.6-3.2] months, p=0.06) and mean pulmonary arterial pressure (T18: 41 [33-49] vs. T21: 35 [30-41] vs. control: 36 [28-43] mmHg, p=0.121) between the groups. The pulmonary to systemic blood flow ratio (Qp/Qs) (p=0.983), Rp (p=0.449), and Cp (p=0.195) did not differ between T18 and control groups. However, Qp/Qs and Cp in T18 group were significantly greater than that in T21 group (T18: Qp/Qs: 3.4 [2.3-5.2] vs. T: 21 2.3 [1.7-3.7], p=0.001. Cp: 3.5 [2.3-5.5] vs. 2.3 [1.6-3.1] mmHg/mL/m2 , p=0.007), while Rp was identical between the groups (T18: 2.0 [1.6-3.3] vs. T21: 2.3 [1.7-3.7], p=0.386). The pulmonary circulation in T18 subjects differed from that observed in T21 subjects, and identical to that observed in control subjects. Pulmonary hypertension is expected to be normalized after reasonable corrective surgery in T18 patients with congenital heart disease.

Arterial stiffness is associated with oxidative stress and endothelial activation among persons with treated HIV in Zambia.

BackgroundCardiovascular disease (CVD) prevalence is rising among persons with HIV (PLWH) in sub-Saharan Africa. Oxidative stress and endothelial activation, resulting in reduced vascular compliance, are contributors to CVD risk. However, there is a paucity of vascular health data in this population.ObjectivesTo assess the relationships of oxidative stress and endothelial activation with vascular stiffness among PLWH.MethodFifty-four PLWH on antiretroviral therapy > 5 years and 57 HIV-negative controls, all aged 18–45 years, were enrolled from the University Teaching Hospital, Lusaka, Zambia. Oxidative stress was measured by nitrotyrosine, a peroxynitrite biomarker, and endothelial activation by soluble intercellular adhesion molecule-1 (sICAM-1) plasma levels. Vascular compliance was measured using carotid-radial pulse wave velocity (crPWV) and arterial stiffness index (crASI).ResultsPLWH had higher sICAM-1 levels (median 345 ng/mL) compared to controls (275 ng/mL, p < 0.01), as well as higher nitrotyrosine levels (297 versus 182 nM; p = 0.02). Median crPWV was similar between the groups, but PLWH had higher crASI (2.4 versus 2.2 cm/ms; p < 0.05). After adjusting for age, fat mass, and blood pressure, the estimated effect of a one unit increase in nitrotyrosine on crPWV were twofold higher in the PLWH, but neither reached significance. In a model pooling all participants, there were significant differences in the relationship of nitrotyrosine with crPWV and crASI by HIV status.ConclusionPLWH in sub-Saharan Africa had significantly greater oxidative stress and endothelial activation compared to HIV-negative individuals. These factors may contribute to increased arterial stiffness and higher CVD prevalence in this population.

Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment.

Background: Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often observed in DM, the vascular dynamics underlying this pathology remain unclear. Thus, we assessed the independent and combined effects of DM status and different vascular hemodynamic measures (i.e., systolic, diastolic, and mean arterial blood pressure and pulse pressure index [PPi]) on WMH burden in cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI).Methods: 559 older adults (mean age: 72.4 years) from the Alzheimer’s Disease Neuroimaging Initiative were categorized into those with diabetes (DM+; CU = 43, MCI = 34) or without diabetes (DM-; CU = 279; MCI = 203). Participants underwent BP assessment, from which all vascular hemodynamic measures were derived. T2-FLAIR MRI was used to quantify WMH burden. Hierarchical linear regression, adjusting for age, sex, BMI, intracranial volume, CSF amyloid, and APOE ε4 status, examined the independent and interactive effects of DM status and each vascular hemodynamic measure on total WMH burden.Results: The presence of DM (p = 0.046), but not PPi values (p = 0.299), was independently associated with greater WMH burden overall after adjusting for covariates. Analyses stratified by cognitive status revealed a significant DM status x PPi interaction within the MCI group (p = 0.001) such that higher PPi values predicted greater WMH burden in the DM + but not DM- group. No significant interactions were observed in the CU group (all ps > 0.05).Discussion: Results indicate that higher PPi values are positively associated with WMH burden in diabetic older adults with MCI, but not their non-diabetic or CU counterparts. Our findings suggest that arterial stiffening and reduced vascular compliance may have a role in development of cerebrovascular pathology within the context of DM in individuals at risk for future cognitive decline. Given the specificity of these findings to MCI, future exploration of the sensitivity of earlier brain markers of vascular insufficiency (i.e., prior to macrostructural white matter changes) to the effects of DM and arterial stiffness/reduced vascular compliance in CU individuals is warranted.

Ability of dynamic preload indices to predict fluid responsiveness in a high femoral-to-radial arterial pressure gradient: a retrospective study.

BackgroundDynamic preload indices may predict fluid responsiveness in end-stage liver disease. However, their usefulness in patients with altered vascular compliance is uncertain. This study is the first to evaluate whether dynamic indices can reliably predict fluid responsiveness in patients undergoing liver transplantation with a high femoral-to-radial arterial pressure gradient (PG).MethodsEighty liver transplant recipients were retrospectively categorized as having a normal (n = 56) or high (n = 24, difference in systolic pressure ≥ 10 mmHg and/or mean pressure ≥ 5 mmHg) femoral-to-radial arterial PG, measured immediately after radial and femoral arterial cannulation. The ability of dynamic preload indices (stroke volume variation, pulse pressure variation [PPV], pleth variability index) to predict fluid responsiveness was assessed before the surgery. Fluid replacement of 500 ml of crystalloid solution was performed over 15 min. Fluid responsiveness was defined as ≥ 15% increase in the stroke volume index. The area under the receiver-operating characteristic curve (AUC) indicated the prediction of fluid responsiveness.ResultsFourteen patients in the normal, and eight in the high PG group were fluid responders. The AUCs for PPV in the normal, high PG groups and total patients were 0.702 (95% confidence interval [CI] 0.553–0.851, P = 0.008), 0.633 (95% CI 0.384–0.881, P = 0.295) and 0.667 (95% CI 0.537–0.798, P = 0.012), respectively. No other index predicted fluid responsiveness.ConclusionPPV can be used as a dynamic index of fluid responsiveness in patients with end-stage liver disease but not in patients with altered vascular compliance.

P105 Endocrine, autonomic and vascular function in children with Sleep Disordered Breathing

Abstract SDB is a risk factor for cardiovascular disease and co-exists with chronic endocrine disorders such as type II diabetes and metabolic syndrome. Children with SDB have increased blood flow velocity, an indicator of reduced vascular compliance and early vascular aging. Increased blood flow velocity is positively associated with sympathetic activity, increased arterial sympathetic nerve fibre density and endothelial damage. Whether changes in endocrine function occur concomitantly with altered autonomic and vascular function in children with SDB was assessed. Thirty six children scheduled for tonsillectomy underwent overnight polysomnography (SDB severity), pupil light reflex (autonomic function), fasting brachial artery blood flow assessment (vascular function - Doppler Ultrasound). Leptin and Ghrelin - both hormonal markers associated with sympathetic activity were measured in urine using ELISA and serum using MagPlex. The following dimensions of the dorsal lingual artery (tonsil) were measured – medial thickness, medial area, smooth muscle cell number/layers. We observed a positive correlation between serum and urine leptin and ghrelin concentrations. Increased blood flow velocity and arterial medial thickness were both associated with increased serum and urine leptin and ghrelin concentrations. Pupil light reflex was negatively associated with serum leptin and ghrelin levels. OAHI was positively correlated with leptin and ghrelin concentration (urine and serum) but not blood flow velocity. Blood flow velocity was inversely correlated with SpO2 nadir (REM). Our findings suggest that SDB has a global effect on the autonomic, vascular and endocrine systems.The impact of untreated paediatric SDB on the development of comorbidities in later life needs urgent attention.

Total Effective Vascular Compliance of a Global Mathematical Model for the Cardiovascular System

In this work, we determined the total effective vascular compliance of a global closed-loop model for the cardiovascular system by performing an infusion test of 500 mL of blood in four minutes. Our mathematical model includes a network of arteries and veins where blood flow is described by means of a one-dimensional nonlinear hyperbolic PDE system and zero-dimensional models for other cardiovascular compartments. Some mathematical modifications were introduced to better capture the physiology of the infusion test: (1) a physiological distribution of vascular compliance and total blood volume was implemented, (2) a nonlinear representation of venous resistances and compliances was introduced, and (3) main regulatory mechanisms triggered by the infusion test where incorporated into the model. By means of presented in silico experiment, we show that effective total vascular compliance is the result of the interaction between the assigned constant physical vascular compliance and the capacity of the cardiovascular system to adapt to new situations via regulatory mechanisms.