Electrophysiology of human iPSC-derived vascular smooth muscle cells and cell autonomous consequences of Cantu Syndrome mutations.

OBJECTIVE: Cantu Syndrome (CS), a multisystem disease with a complex cardiovascular phenotype, is caused by GoF variants in the Kir6.1/SUR2 subunits of ATP-sensitive potassium (KATP) channels, and is characterized by low systemic vascular resistance, as well as tortuous, dilated vessels, and decreased pulse-wave velocity. Thus, CS vascular dysfunction is multifactorial, with both hypomyotonic and hyperelastic components. To dissect whether such complexities arise cell-autonomously within vascular smooth muscle cells (VSMCs), or as secondary responses to the pathophysiological milieu, we assessed electrical properties and gene expression in human induced pluripotent stem cell-derived VSMCs (hiPSC-VSMCs), differentiated from control and CS patient-derived hiPSCs, and in native mouse control and CS VSMCs. APPROACH AND RESULTS: Whole-cell voltage-clamp of isolated aortic and mesenteric arterial VSMCs isolated from wild type (WT) and Kir6.1[V65M] (CS) mice revealed no clear differences in voltage-gated K+ (Kv) or Ca2+ currents. Kv and Ca2+ currents were also not different between validated hiPSC-VSMCs differentiated from control and CS patient-derived hiPSCs. While pinacidil-sensitive KATP currents in control hiPSC-VSMCs were consistent with those in WT mouse VSMCs, they were considerably larger in CS hiPSC-VSMCs. Under current-clamp conditions, CS hiPSC-VSMCs were also hyperpolarized, consistent with increased basal K conductance, and providing an explanation for decreased tone and decreased vascular resistance in CS. Increased compliance was observed in isolated CS mouse aortae, and was associated with increased elastin mRNA expression. This was consistent with higher levels of elastin mRNA in CS hiPSC-VSMCs, suggesting that the hyperelastic component of CS vasculopathy is a cell-autonomous consequence of vascular KATP GoF. CONCLUSIONS: The results show that hiPSC-VSMCs reiterate expression of the same major ion currents as primary VSMCs, validating the use of these cells to study vascular disease. Results in hiPSC-VSMCs derived from CS patient cells suggest that both the hypomyotonic and hyperelastic components of CS vasculopathy are cell-autonomous phenomena driven by KATP overactivity within VSMCs.

No influence of steady-state postural changes on cerebrovascular compliance in humans.

The aim of this study was to determine the effect of posture changes on vascular compliance in intracranial (brain) versus extracranial vascular beds (forearm). Eighteen young adults (nine females) performed a supine-to-seated-to-standing protocol involving 5 min of rest in each position. Continuous blood pressure, middle cerebral artery (MCA) blood velocity, and brachial artery blood velocity were recorded at each posture. Three to five consecutive steady-state cardiac cycles at each posture were analyzed by a four-element lumped parameter modified Windkessel model to calculate vascular compliance. Mean arterial pressure (MAP) increased from supine to seated (76(9) vs. 81(12) mmHg; P = 0.006) and from supine to standing (76(9) vs. 82(13) mmHg; P = 0.034). Mean blood flow was greater in the MCA relative to the forearm (forearm: 40(5) mL·min-1, MCA: 224(17) mL·min-1; main effect P < 0.001). Conversely, vascular resistance (forearm: 3.25(0.50) mmHg-1·mL·min-1, brain: 0.36(0.04) mmHg-1·mL·min-1; main effect P < 0.001) and compliance (forearm: 0.010(0.001) mL·min-1·mmHg-1, brain: 0.005(0.001) mL·min-1·mmHg-1; main effect P = 0.001) were greater in the forearm compared to the brain. Significant main effects of posture were observed with decreasing values in upright positions for mean blood flow (P = 0.001) in both vascular beds, but not for resistance (P = 0.163) or compliance (P = 0.385). There were no significant interaction effects between vascular bed and posture for mean flow (P = 0.057), resistance (P = 0.258), or compliance (P = 0.329). This study provides evidence that under steady-state conditions, posture does not affect cerebrovascular compliance.

Pulsative venous return from the branchial vessels to the heart of the bivalve Mytilus galloprovincialis supports the constant-volume mechanism.

In bivalves and gastropods, ventricle contraction causes a negative pressure in the auricles and increases venous return from the afferent oblique vein (AOV): the constant-volume (CV) mechanism. The flow in the AOV should be a pulsative flow synchronized with the ventricular contraction. The flow in the heart and adjacent vessels of Mytilus galloprovincialis were measured by magnetic resonance imaging to confirm this hypothesis. Under a regular heartbeat, pulsative flows in the AOV and branchial vessels (BVs) were almost completely synchronized with the flow in the aorta, while filling of the ventricle was in the opposite phase. Flows in the BVs were directed to the posterior direction, and a pair of BVs in the gill axes (the efferent BVs) were connected to the AOV. Based on the images of the whole pathway of the AOV in an oblique slice, we confirmed that haemolymph flow was evoked from the efferent BVs and flow into the ventricle via the auricle was completed in a single heartbeat. Therefore, the walls of the AOV and BVs could resist negative transmural pressure caused by the ventricular contraction. In conclusion, the auricle, the AOV and the BVs, including the gill filaments, act as a suction pump. The pulsative venous return is driven by the negative pressure of the AOV as in the CV mechanism, and the negative pressure in the efferent BVs could draw haemolymph from the sinus via the gill and the afferent BVs. Therefore, Mytilus can start and stop its heartbeat as necessary.

Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance.

We have reviewed the development and current status of therapies based on exposure to non-ionizing radiation (with a photon energy less than 10 eV) aimed at suppressing the venous neointimal hyperplasia, and consequentially at avoiding stenosis in arteriovenous grafts. Due to the drawbacks associated with the medical use of ionizing radiation, prominently the radiation-induced cardiovascular disease, the availability of procedures using non-ionizing radiation is becoming a noteworthy objective for the current research. Further, the focus of the review was the use of such procedures for improving the vascular access function and assuring the clinical success of arteriovenous fistulae in hemodialysis patients. Following a brief discussion of the physical principles underlying radiotherapy, the current methods based on non-ionizing radiation, either in use or under development, were described in detail. There are currently five such techniques, including photodynamic therapy (PDT), far-infrared therapy, photochemical tissue passivation (PTP), Alucent vascular scaffolding, and adventitial photocrosslinking. The last three are contingent on the mechanical stiffening achievable by the exogenous photochemical crosslinking of tissular collagen, a process that leads to the decrease of venous compliance. As there are conflicting opinions on the role of compliance mismatch between arterial and venous conduits in a graft, this aspect was also considered in our review.

Impact of ischemic heart disease and cardiac rehabilitation on cerebrovascular compliance.

We aimed to determine the influence of ischemic heart disease (IHD) and cardiac rehabilitation (CR) on cerebrovascular compliance index (Ci). Eleven (one female) patients with IHD (mean[SD]: 61[11] yr, 29[4] kg/m2) underwent 6 mo of CR, which consisted of ≥3 sessions/wk of aerobic and resistance training (20-60 min each). Ten (three female) similarly aged controls (CON) were tested at baseline as a comparator group. Middle cerebral artery velocity (MCAv) and mean arterial pressure were monitored continuously using transcranial Doppler ultrasound and finger photoplethysmography, respectively, during a rapid sit-to-stand maneuver. A Windkessel model was used to estimate cerebrovascular Ci every five cardiac cycles for a duration of 30 s. Cerebrovascular resistance was calculated as the quotient of MAP and MCAv. Two-way ANOVAs were used to determine whether cerebrovascular variables differ during postural transitions between groups and after CR. Baseline MCAv was higher in CON versus IHD (P = 0.014) and a time × group interaction was observed (P = 0.045) where MCAv decreased more in CON after standing. Compared with the precondition, CR had no effect on MCAv (condition P = 0.950) but a main effect of time indicated that MCAv decreased from the seated position in both conditions (time P = 0.013). Baseline cerebrovascular Ci was greater in IHD versus CON (P = 0.049) and the peak cerebrovascular Ci during the transition to standing was significantly higher in IHD compared with CON (interaction P = 0.047). CR did not affect cerebrovascular compliance (P = 0.452) and no time-by-condition interaction upon standing was present (P = 0.174). Baseline cerebrovascular Ci is higher in IHD at baseline compared with CON, but 6 mo of CR did not modify the transient increase in cerebrovascular Ci during sit-to-stand maneuvers.NEW & NOTEWORTHY Post-cardiac event cognitive impairment is common and exercise-based rehabilitation may be an effective intervention to mitigate cognitive decline. Microvascular damage due to high blood pressure pulsatility entering the brain is the putative mechanism of vascular dementia. Whether patients with ischemic heart disease exhibit lower cerebrovascular compliance, and if cardiac rehabilitation can improve cerebrovascular compliance is unknown. We observed that patients with ischemic heart disease have paradoxically higher cerebrovascular compliance, which is not affected by cardiac rehabilitation.

Endothelium-dependent relaxation is impaired in Schlager hypertensive (BPH/2J) mice by region-specific mechanisms in conductance and resistance arteries.

AIMS: Endothelial dysfunction and arterial stiffness are hallmarks of hypertension, and major risk factors for cardiovascular disease. BPH/2J (Schlager) mice are a genetic model of spontaneous hypertension, but little is known about the vascular pathophysiology of these mice and the region-specific differences between vascular beds. Therefore, this study compared the vascular function and structure of large conductance (aorta and femoral) and resistance (mesenteric) arteries of BPH/2J mice with their normotensive BPN/2J counterparts. MAIN METHODS: Blood pressure was measured in BPH/2J and BPN/3J mice via pre-implanted radiotelemetry probes. At endpoint, vascular function and passive mechanical wall properties were assessed using wire and pressure myography, qPCR and histology. KEY FINDINGS: Mean arterial blood pressure was elevated in BPH/2J mice compared to BPN/3J controls. Endothelium-dependent relaxation to acetylcholine was attenuated in both the aorta and mesenteric arteries of BPH/2J mice, but through different mechanisms. In the aorta, hypertension reduced the contribution of prostanoids. Conversely, in the mesenteric arteries, hypertension reduced the contribution of both nitric oxide and endothelium-dependent hyperpolarization. Hypertension reduced volume compliance in both femoral and mesenteric arteries, but hypertrophic inward remodelling was only observed in the mesenteric arteries of BPH/2J mice. SIGNIFICANCE: This is the first comprehensive investigation of vascular function and structural remodelling in BPH/2J mice. Overall, hypertensive BPH/2J mice exhibited endothelial dysfunction and adverse vascular remodelling in the macro- and microvasculature, underpinned by distinct region-specific mechanisms. This highlights BPH/2J mice as a highly suitable model for evaluating novel therapeutics to treat hypertension-associated vascular dysfunction.

A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling.

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential. Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts, it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration. The size of pores within implanted biomaterials has shown significant effects on macrophage polarization, which has been further confirmed as necessary for efficient vascular formation and remodeling. Here, we developed biodegradable, autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts' interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate. The synthetic vascular grafts showed similar mechanical properties to native blood vessels, encouraged macrophage populations with varying M2 to M1 phenotypic expression, and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model. This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.

Regulation of cerebrovascular compliance compared with forearm vascular compliance in humans: a pharmacological study.

Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (Ci) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased Ci similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular Ci (72 ± 61%) and forearm vascular Ci (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased Ci but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm.NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain.

Feasibility to estimate mean systemic filling pressure with inspiratory holds at the bedside.

Background: A decade ago, it became possible to derive mean systemic filling pressure (MSFP) at the bedside using the inspiratory hold maneuver. MSFP has the potential to help guide hemodynamic care, but the estimation is not yet implemented in common clinical practice. In this study, we assessed the ability of MSFP, vascular compliance (Csys), and stressed volume (Vs) to track fluid boluses. Second, we assessed the feasibility of implementation of MSFP in the intensive care unit (ICU). Exploratory, a potential difference in MSFP response between colloids and crystalloids was assessed. Methods: This was a prospective cohort study in adult patients admitted to the ICU after cardiac surgery. The MSFP was determined using 3-4 inspiratory holds with incremental pressures (maximum 35 cm H2O) to construct a venous return curve. Two fluid boluses were administered: 100 and 500 ml, enabling to calculate Vs and Csys. Patients were randomized to crystalloid or colloid fluid administration. Trained ICU consultants acted as study supervisors, and protocol deviations were recorded. Results: A total of 20 patients completed the trial. MSFP was able to track the 500 ml bolus (p < 0.001). In 16 patients (80%), Vs and Csys could be determined. Vs had a median of 2029 ml (IQR 1605-3164), and Csys had a median of 73 ml mmHg-1 (IQR 56-133). A difference in response between crystalloids and colloids was present for the 100 ml fluid bolus (p = 0.019) and in a post hoc analysis, also for the 500 ml bolus (p = 0.010). Conclusion: MSFP can be measured at the bedside and provides insights into the hemodynamic status of a patient that are currently missing. The clinical feasibility of Vs and Csys was judged ambiguously based on the lack of required hemodynamic stability. Future studies should address the clinical obstacles found in this study, and less-invasive alternatives to determine MSFP should be further explored. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03139929.

Effects of a 12-Week Periodized Resistance Training Program on Resting Brain Activity and Cerebrovascular Function: A Nonrandomized Pilot Trial.

Resistance training is a promising strategy to promote healthy cognitive aging; however, the brain mechanisms by which resistance training benefits cognition have yet to be determined. Here, we examined the effects of a 12-week resistance training program on resting brain activity and cerebrovascular function in 20 healthy older adults (14 females, mean age 69.1 years). In this single group clinical trial, multimodal 3 T magnetic resonance imaging was performed at 3 time points: baseline (preceding a 12-week control period), pre-intervention, and post-intervention. Along with significant improvements in fluid cognition (d = 1.27), 4 significant voxelwise clusters were identified for decreases in resting brain activity after the intervention (Cerebellum, Right Middle Temporal Gyrus, Left Inferior Parietal Lobule, and Right Inferior Parietal Lobule), but none were identified for changes in resting cerebral blood flow. Using a separate region of interest approach, we provide estimates for improved cerebral blood flow, compared with declines over the initial control period, in regions associated with cognitive impairment, such as hippocampal blood flow (d = 0.40), and posterior cingulate blood flow (d = 0.61). Finally, resistance training had a small countermeasure effect on the age-related progression of white matter lesion volume (rank-biserial = -0.22), a biomarker of cerebrovascular disease. These proof-of-concept data support larger trials to determine whether resistance training can attenuate or even reverse salient neurodegenerative processes.

Femoral Pulse Pressure Variation Is Not Interchangeable with Radial Pulse Pressure Variation during Living Donor Liver Transplantation.

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has not rather than never studied in patients undergoing liver transplantation whether PPV measured at peripheral sites, such as the radial artery, do represent central PPV for evaluating blood volume. In this retrospective study, 51 liver transplant recipients were enrolled. The two PPVs had been automatically recorded every minute in electrical medical records. A total 1878 pairs of the two PPVs were collected. The interchangeability of PPV measured at the radial and the femoral artery was analyzed by using the Bland−Altman plot, four-quadrant plot, Cohen's kappa (k), and receiver operating curve. The bias and limits of agreement of the two PPVs were −1.3% and −8.8% to 6.2%, respectively. The percentage error was 75%. The concordance rate was 65%. The Kappa of PPV-radial determining whether PPV-femoral was >13% or ≤13% was 0.64. We found that PPV-radial is not interchangeable with PPV-femoral during liver transplantation. Additionally, PPV-radial failed to reliably track changes of PPV-femoral. Lastly, the clinical decision regarding blood volume status (depletion or not) is significantly different between the two PPVs. Therefore, PPV-femoral may help maintain blood volume circulating to major organs including the newly transplanted liver graft for liver transplant recipients.

Phenotyping exercise limitation of patients with Interstitial Fibrosing Lung Disease: the importance of exercise hemodynamics.

INTRODUCTION AND OBJECTIVE: Left-heart dysfunction and pulmonary vasculopathy are increasingly recognized as contributing factors of exercise capacity limitation in interstitial fibrosing lung disease (IFLD). Moreover, the clinical significance of exercise pulmonary hypertension (ePH) in pulmonary and cardiac diseases has been documented, representing a risk factor for decreased exercise capacity and survival, progression to resting pulmonary hypertension (PH) and overall clinical worsening. We conducted a prospective study aiming at: (a) assessing the prevalence of PH and ePH in a cohort of 40 functionally limited patients with IFLD, (b) determining the post-capillary (postC) or pre-capillary (preC) etiology of either PH or ePH in this cohort, and (c) examining the correlations between invasively and non-invasively measured exercise variables among hemodynamic groups. PATIENTS AND METHODS: 40 IFLD patients underwent cardiopulmonary evaluation, including: clinical examination, lung function tests, 6-minute walking test, heart ultrasonography, cardiopulmonary exercise test and, finally, right heart catheterization (RHC). Resting hemodynamic evaluation was followed by the exercise protocol proposed by Herve et al, using a bedside cycle ergometer in the supine position. Abnormal elevation of mean pulmonary artery pressure (mPAP) above 30mmHg during exercise, with respect to abnormal elevation of cardiac output (CO) below 10 L/min (mPAP-CO ratio ⩾3 mmHg·min·L-1) was used to define ePH (Herve et al, 2015). Secondary hemodynamic evaluation involved detection of abnormal pulmonary arterial wedge pressure (PAWP) increase at peak exercise in relation to CO. Specifically, ΔPAWP/ΔCO >2 mmHg/L per minute determined an abnormal PAWP elevation (Bentley et al, 2020). RESULTS: Among the 40-patient cohort, 25% presented postC PH, 37.5% preC PH, 27.5% ePH, with the remaining 10% recording normal hemodynamics. PAWP evaluation during exercise revealed a postC etiology in 4 out of the 11 patients presenting ePH, and a postC etiology in 6 out of the 15 patients presenting resting preC PH. Mean values of non-invasive variables did not display statistically significant differences among hemodynamic groups, except for: diffusing capacity for carbon monoxide (DLCO), carbon monoxide transfer coefficient (KCO) and the ratio of functional vital capacity to DLCO (FVC%/DLCO%), which were lower in both ePH and PH groups (p < 0.05). Resting values of CO, cardiac index (CI), stroke volume (SV) and pulmonary vascular compliance (PVC) were significantly impaired in ePH, preC-PH and postC-PH groups when compared to the normal group. CONCLUSIONS: Both PH and ePH were highly prevalent within the IFLD patient group, suggesting that RHC should be offered more frequently in functionally limited patients. Diffusion capacity markers must thus guide decision making, in parallel to clinical evaluation. ePH was associated to lower resting CO and PVC, in a similar way to resting PH, indicating the relevance of cardiopulmonary function to exercise limitation. Finally, the use of the ΔPAWP/ΔCO>2 criterion further uncovered PH of postcapillary etiology, highlighting the complexity of hemodynamics in IFLD. CLINICALTRIALS: gov ID: NCT03706820.

Acute changes in forearm vascular compliance during transient sympatho-excitation.

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho-excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end-inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post-exercise circulatory occlusion (SHG + PECO; measured in the non-exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho-excitation, but in a reflex-dependent manner.

Human Hypertension Blood Flow Model Using Fractional Calculus.

The blood flow dynamics in human arteries with hypertension disease is modeled using fractional calculus. The mathematical model is constructed using five-element lumped parameter arterial Windkessel representation. Fractional-order capacitors are used to represent the elastic properties of both proximal large arteries and distal small arteries measured from the heart aortic root. The proposed fractional model offers high flexibility in characterizing the arterial complex tree network. The results illustrate the validity of the new model and the physiological interpretability of the fractional differentiation order through a set of validation using human hypertensive patients. In addition, the results show that the fractional-order modeling approach yield a great potential to improve the understanding of the structural and functional changes in the large and small arteries due to hypertension disease.

Cardiovascular profiles associated with white matter hyperintensities in healthy young women.

Women who experience hypertension in pregnancy have increased risk of both chronic hypertension and dementia. High blood pressure is associated with increased evidence of white matter hyperintensities (WMH) in brain imaging. WMH are disruptions of the white matter of the brain that occur with demyelination and axonal degeneration, are associated with vascular disease, occur more frequently in people with hypertension, and are associated with cognitive impairment. We evaluated the relationship between WMH and subclinical cardiovascular function in healthy young nulliparous women and women with a history of early-onset preeclampsia. Sixty-two reproductive-aged women were assessed during the follicular phase of the menstrual cycle after a 3-day sodium/potassium-controlled diet. Half of participants had a history of early-onset preeclampsia, and half were nulliparous. Blood was drawn to assess inflammatory markers. Cardiovascular assessments included tonometric blood pressure monitoring, volume loading to assess vascular compliance, echocardiography to assess cardiac ejection time, brachial pulse wave velocity of the brachial artery, assessing cardiovascular stiffness, and brachial artery flow mediated vasodilation to assess endothelial mediated dilatory response. T2 fluid-attenuated inversion recovery (FLAIR) MRI imaging was obtained. Two raters, blinded to cardiovascular assessments and pregnancy history, reviewed MRI scans for evidence of WMH using the Fazekas rating scale. WMHs were detected in 17 women; 45 had normal white matter structure. Participants with Fazekas score>0 had exaggerated response to volume loading compared to women with a Fazekas score of 0 and longer cardiac ejection times. Fazekas scores >0 had lower brachial flow-mediated vasodilation and increased white blood count compared to those with no evidence of WMH. Women with WMH had reduced cardiovascular compliance, and a trend towards decreased endothelial responsiveness compared to those without WMH. These data demonstrated that the relationship between cardiovascular and brain health was detectable in young, healthy, reproductive-aged women, and may play a role in later development of clinical disease. These findings may help identify women who are at risk for cognitive decline and pathological aging.

Angioplasty Induced Changes in Dialysis Vascular Access Compliance.

Dialysis vascular access remains vitally important to maintain life and functional capacity with end stage renal disease. Angioplasty is an integral part of maintaining dialysis access function and patency. To understand the effect of angioplasty balloon dilation on vascular wall mechanics, we conducted a clinical study to evaluate the elastic modulus of the anastomosis in five subjects with anastomosis stenoses, before and after six angioplasty procedures, using B-mode ultrasound DICOM data. A novel and open source vascular ultrasound high-resolution speckle tracking software tool was used. The median lumen diameter increased from 3.4 to 5.5 mm after angioplasty. Meanwhile, the median elastic modulus of the 18 measurements at the anastomosis increased by 52.2%, from 2.24 × 103 to 3.41 × 103 mmHg. The results support our hypothesis that the structural changes induced in the vessel wall by balloon dilation lead to reduced vascular compliance and a higher elastic modulus of the vessel wall.

Vasodilatation by carbon dioxide and sodium nitroglycerin reduces compliance of the cerebral arteries in humans.

NEW FINDINGS: What is the central question of this study? Vascular compliance importantly contributes to the regulation of cerebral perfusion and complex mechanisms are known to influence compliance of a vascular bed: while vasodilatation mediates changes in vascular resistance, does it also affect compliance, particularly in the cerebral vasculature? What is the main finding and its importance? Cerebral vasodilatation, elicited by hypercapnia and sodium nitroglycerin administration, reduced cerebrovascular compliance by approximately 26% from baseline. This study provides new insight into mechanisms mediating cerebrovascular compliance. ABSTRACT: Changes in vascular resistance and vascular compliance contribute to the regulation of cerebral perfusion. While changes in vascular resistance are known to be mediated by vasodilatation, the mechanisms contributing to changes in vascular compliance are complex. In particular, whether vasodilatation affects compliance of the vasculature within the cranium remains unknown. Therefore, the present study examined the impact of two vasodilatation pathways on cerebrovascular compliance in humans. Fifteen young, healthy adults (26 ± 5 years, seven females) completed two protocols: (i) sublingual sodium nitroglycerin (SNG; 0.4 mg) and (ii) hypercapnia (5-6% carbon dioxide gas mixture for 4 min). Blood pressure waveforms (finger photoplethysmography) and middle cerebral artery blood velocity waveforms (transcranial Doppler ultrasound) were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci decreased 24 ± 17% from baseline ((5.0 ± 2.3) × 10-4  cm s-1  mmHg-1 ) to minute 10 ((3.6 ± 1.2) × 10-4  cm s-1  mmHg-1 ; P = 0.009). During the hypercapnia protocol, Ci decreased 28 ± 9% from baseline ((4.4 ± 1.9) × 10-4  cm s-1  mmHg-1 ) to minute 4 ((3.1 ± 1.4) × 10-4  cm s-1  mmHg-1 ; P < 0.001). Cerebral vasodilatory stimuli induced by nitric oxide and carbon dioxide mechanisms reduced compliance of the cerebral vascular bed by approximately 26% from supine baseline values.

Three-dimensional assessment of brain arterial compliance: Technical development, comparison with aortic pulse wave velocity, and age effect.

PURPOSE: The ability to measure cerebral vascular compliance (VC) is important in the evaluation of vascular diseases. Additionally, quantification of arterial wall pulsation in the brain may be useful for understanding the driving force of the recently discovered glymphatic system. Our goal is to develop an MRI technique to measure VC and arterial wall pulsation in major intracranial vessels. METHODS: A total of 17 healthy subjects were studied on a 3T MRI system. The technique, called VaCom-PCASL, uses pseudo-continuous arterial spin labeling (PCASL) to obtain pure blood vessel signal, uses a 3D radial acquisition, and applies a golden-angle radial sparse parallel (GRASP) algorithm for image reconstruction. The k-space data were retrospectively sorted into different cardiac phases. The GRASP algorithm allows the reconstruction of 5D (three spatial dimensions, one control/label dimension, and one cardiac-phase dimension) data simultaneously. The proposed technique was optimized in terms of reconstruction parameters and labeling duration. Intracranial VC was compared with aortic pulse wave velocity measured with phase-contrast MRI. Age differences in VC were studied. RESULTS: The VaCom-PCASL technique using 10 cardiac phases and GRASP sparsity constraints of λlabel/control = 0.05 and λcardiac = 0.05 provided the highest contrast-to-noise ratio. A labeling duration of 800 ms was found to yield signals comparable to those of longer duration (P > .2), whereas 400 ms yielded significant overestimation (P < .005). A significant correlation was observed between intracranial VC and aortic pulse wave velocity (r = -0.73, P = .038, N = 8). Vascular compliance in the older group was lower than that in the younger group. CONCLUSION: The VaCom-PCASL-MRI technique represents a promising approach for noninvasive assessment of arterial stiffness and pulsatility.

Aging and Vascular Compliance in Hypertensive Patients Mirrored in Routine Investigations.

The global prevalence of arterial hypertension is increasing. Due to its consequences, hypertension is a leading cause of morbidity /mortality. In this regard, awareness of the importance of diagnosis as well as proper treatment of hypertension is mandatory. OBJECTIVES: This study aims to analyze vascular compliance and different pressure characteristics depending on age, along with highlighting some clinical-paraclinical correlations in people diagnosed with hypertension. We used usual laboratory analyzes and the blood pressure values obtained using ABPM/24 hr, in addition to highlighting the impact of age on those parameters. MATERIALS AND METHODS: The sample comprises of 99 adults diagnosed with hypertension. We divided them into 2 groups, according to age: cases sample: 52 patients (age> 60 years old) and control sample: 47 patients (age< 60 years old). RESULTS: In the control group, RDW was correlated with the general and diurnal systolic and diastolic hypertonicity indexes and the platelet count was positively correlated only with the morning surge. The dipping profile correlates negatively with RDW. In the elderly, all three systolic blood pressure parameters are influenced by ESR and also correlate negatively with HDL, with an inverse proportional relationship. Statistically significant correlations were found between blood glucose and diurnal systolic and diastolic hypertonicity indexes. Mean Pulse Pressure correlates in the elderly with HDL (negative correlations) and in the young with RDW (positive correlations). CONCLUSIONS: Vascular compliance can be estimated with the help of HDL in the elderly and RDW in young people, considering the influence of the two parameters on pulse pressure.

Multiple short bouts of exercise are better than a single continuous bout for cardiometabolic health: a randomised crossover trial.

PURPOSE: To compare cardiometabolic responses to five consecutive days of daily postprandial exercise accumulated in three 10-min bouts or a single 30-min bout to a no-exercise control. METHODS: Ten insufficiently active adults completed three trials in a randomised order. Each trial comprised five consecutive days of 30 min of exercise either accumulated in three separate 10-min bouts (ACC) after main meals; a single 30-min bout after dinner (CONT); or a no-exercise control (NOEX). Glucose regulation was assessed from an oral glucose tolerance test. Applanation tonometry was used to assess pulse wave velocity approximately 12 h following completion of the final trial. RESULTS: Area under the 2-h glucose curve was similar for CONT (mean; 95% CI 917 mmol L-1 2 h-1; 815 to 1019) and ACC (931 mmol L-1 2 h-1; 794 to 1068, p = 0.671). Area under the 2-h insulin curve was greater following NOEX (70,328 pmol L-1 2 h-1; 30,962 to 109,693) than ACC (51,313 pmol L-1 2 h-1: 21,822 to 80,806, p = 0.007). Pulse wave velocity was lower for ACC (5.96 m s-1: 5.38 to 6.53) compared to CONT (6.93 m s-1: 5.92 to 7.94, p = 0.031) but not significantly lower for ACC compared to NOEX (6.52 m s-1: 5.70 to 7.34, p = 0.151). CONCLUSION: Accumulating 30 min of moderate-intensity walking in three bouts throughout the day is more effective at reducing markers of cardiometabolic health risk in insufficiently active, apparently healthy adults than a single daily bout. Both accumulated and single-bout walking were equally as effective at reducing postprandial glucose concentrations compared to a no-exercise control. Therefore, accumulating exercise in short bouts after each main meal might be more advantageous for overall cardiometabolic health.