The antidiabetic drug ipragliflozin induces vasorelaxation of rabbit femoral artery by activating a Kv channel, the SERCA pump, and the PKA signaling pathway.

We explored the vasorelaxant effects of ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, on rabbit femoral arterial rings. Ipragliflozin relaxed phenylephrine-induced pre-contracted rings in a dose-dependent manner. Pre-treatment with the ATP-sensitive K+ channel inhibitor glibenclamide (10 µM), the inwardly rectifying K+ channel inhibitor Ba2+ (50 µM), or the Ca2+-sensitive K+ channel inhibitor paxilline (10 µM) did not influence the vasorelaxant effect. However, the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (3 mM) reduced the vasorelaxant effect. Specifically, the vasorelaxant response to ipragliflozin was significantly attenuated by pretreatment with the Kv7.X channel inhibitors linopirdine (10 µM) and XE991 (10 µM), the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin (1 µM) and cyclopiazonic acid (10 µM), and the cAMP/protein kinase A (PKA)-associated signaling pathway inhibitors SQ22536 (50 µM) and KT5720 (1 µM). Neither the cGMP/protein kinase G (PKG)-associated signaling pathway nor the endothelium was involved in ipragliflozin-induced vasorelaxation. We conclude that ipragliflozin induced vasorelaxation of rabbit femoral arteries by activating Kv channels (principally the Kv7.X channel), the SERCA pump, and the cAMP/PKA-associated signaling pathway independent of other K+ (ATP-sensitive K+, inwardly rectifying K+, and Ca2+-sensitive K+) channels, cGMP/PKG-associated signaling, and the endothelium.

Value and Variability of Pulse Shape Indicator for Estimating Mean Arterial Pressure in the Radial and Femoral Arteries.

BACKGROUND: The form factor (FF) is a pulse shape indicator that corresponds to the fraction of pulse pressure added to diastolic blood pressure to estimate the time-averaged mean arterial pressure (MAP). Our invasive study assessed the FF value and variability at the radial and femoral artery levels and evaluated the recommended fixed FF value of 0.33. METHODS AND RESULTS: Hemodynamically stable patients were prospectively included in 2 intensive care units. FF was documented at baseline and during dynamic maneuvers. A total of 632 patients (64±16 years of age, 66% men, MAP=81±14 mm Hg) were included. Among them, 355 (56%) had a radial catheter and 277 (44%) had a femoral catheter. The FF was 0.34±0.06. In multiple linear regression, FF was influenced by biological sex (P<0.0001) and heart rate (P=0.04) but not by height, weight, or catheter location. The radial FF was 0.35±0.06, whereas the femoral FF was 0.34±0.05 (P=0.08). Both radial and femoral FF were higher in women than in men (P<0.05). When using the 0.33 FF value to estimate MAP, the error was -0.4±4.0 mm Hg and -0.1±2.9 mm Hg at the radial and femoral level, respectively, and the MAP estimate still demonstrated high accuracy and good precision even after changes in norepinephrine dose, increase in positive end-expiratory pressure level, fluid administration, or prone positioning (n=218). CONCLUSIONS: Despite higher FF in women and despite interindividual variability in FF, using a fixed FF value of 0.33 yielded accurate and precise estimations of MAP. This finding has potential implications for blood pressure monitoring devices and the study of pulse wave amplification.

Enhanced external counterpulsation treatment regulates blood flow and wall shear stress metrics in femoral artery: An in vivo study in healthy subjects.

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries.

Genetic background influences arterial vasomotor function in male and female mice.

The purpose of this study was to assess the influence of genetic background and sex on nitric oxide (NO)-mediated vasomotor function in arteries from different vascular territories. Vasomotor function was assessed in thoracic aorta, abdominal aorta, carotid arteries, and femoral arteries from the following mouse strains: SJL/J, DBA/2J, NZW/LacJ, and C57BL/6J. Contractile responses were assessed using the α1-adrenergic receptor agonist phenylephrine (PE, 10-9 -10-5 M). Vasorelaxation responses were assessed by examining relaxation to an endothelium-dependent vasodilator acetylcholine (ACh, 10-9 -10-5 M) and an endothelium-independent vasodilator sodium nitroprusside (SNP, 10-9 -10-5 M). To evaluate the role of NO, relaxation responses to ACh and SNP were assessed in the absence or presence of a nitric oxide synthase inhibitor (N omega-nitro-l-arginine methyl ester hydrochloride: 10-4 M). Vasomotor responses to ACh and PE varied across strains and among the arteries tested with some strains exhibiting artery-specific impairment. Results indicated some concentration-response heterogeneity in response to ACh and SNP between vessels from females and males, but no significant differences in responses to PE. Collectively, these findings indicate that vasomotor responses vary by genetic background, sex, and artery type.

Quantitative and large-format histochemistry to characterize peripheral artery compositional gradients.

The femoropopliteal artery (FPA) is a long, flexible vessel that travels down the anteromedial compartment of the thigh as the femoral artery and then behind the kneecap as the popliteal artery. This artery undergoes various degrees of flexion, extension, and torsion during normal walking movements. The FPA is also the most susceptible peripheral artery to atherosclerosis and is where peripheral artery disease manifests in 80% of cases. The connection between peripheral artery location, its mechanical flexion, and its physiological or pathological biochemistry has been investigated for decades; however, histochemical methods remain poorly leveraged in their ability to spatially correlate normal or abnormal extracellular matrix and cells with regions of mechanical flexion. This study generates new histological image processing pipelines to quantitate tissue composition across high-resolution FPA regions-of-interest or low-resolution whole-section cross-sections in relation to their anatomical locations and flexions during normal movement. Comparing healthy ovine femoral, popliteal, and cranial-tibial artery sections as a pilot, substantial arterial contortion was observed in the distal popliteal and cranial tibial regions of the FPA which correlated with increased vascular smooth muscle cells and decreased elastin content. These methods aim to aid in the quantitative characterization of the spatial distribution of extracellular matrix and cells in large heterogeneous tissue sections such as the FPA. RESEARCH HIGHLIGHTS: Large-format histology preserves artery architecture. Elastin and smooth muscle content is correlated with distance from heart and contortion during flexion. Cell and protein analyses are sensitive to sectioning plane and image magnification.

Renal vascular conductance is unrelated to leg vascular conductance or muscle sympathetic nerve activity at rest and during stress in humans.

The sympathetic nervous system is important for cardiovascular regulation, particularly during acute stress. Efferent sympathetic outflow can be regulated in an organ-dependent manner, but whether renal and leg vasoconstriction are associated at rest or during sympathetic stressors is unknown. Therefore, we sought to determine the relationships between muscle sympathetic nerve activity (MSNA), leg vascular conductance (LVC), and renal vascular conductance (RVC) at rest and during common laboratory-based sympathoexcitatory stimuli in a cohort of young healthy adults. Beat-to-beat arterial pressure (photoplethysmography), MSNA (microneurography), superficial femoral artery blood flow, and renal artery blood velocity (Doppler ultrasound) were measured at rest and during static handgrip exercise (30% maximal voluntary contraction), postexercise circulatory occlusion (PECO), and cold stress (hand in 3.8 ± 1.3°C water) in 37 young healthy adults (16 females, 21 males). At rest, RVC was unrelated to LVC (r = -0.11, P = 0.55) or MSNA burst frequency (ρ = -0.22, P = 0.26). Static handgrip, PECO, and cold stress each induced an increase in mean arterial pressure and MSNA and a reduction in RVC (all P < 0.001). LVC was unaltered during stress (all P ≥ 0.16), with the exception of a reduction during the second minute of cold stress (P = 0.03). During stress, changes in RVC were not associated with changes in LVC (handgrip: r = -0.24, P = 0.21; PECO: ρ = -0.04, P = 0.82; cold stress: r = -0.17, P = 0.38) or MSNA (handgrip: ρ = -0.14, P = 0.48; PECO: r = 0.27, P = 0.15; cold stress: r = -0.27, P = 0.16). Furthermore, MSNA was not associated with LVC at rest or during stress (all P ≥ 0.12). The present findings highlight the differential control of regional sympathetic vasoconstriction at rest and during stress in young healthy humans.NEW & NOTEWORTHY The sympathetic nervous system plays a critical role in cardiovascular regulation at rest and during stress. We demonstrate that renal artery vascular conductance is unrelated to superficial femoral artery vascular conductance or muscle sympathetic nerve activity at rest or during laboratory-based sympathetic stressors in young healthy adults. These findings support the concept of differential control of peripheral sympathetic outflow at rest and during stress in humans.

Effects of Sex and Cuff Pressure on Physiological Responses during Blood Flow Restriction Resistance Exercise in Young Adults.

PURPOSE: The purpose of this study was to examine the physiological responses resulting from an acute blood flow restriction resistance exercise bout with two different cuff pressures in young, healthy men and women. METHODS: Thirty adults (18-30 yr) completed a bilateral leg extension blood flow restriction bout consisting of four sets (30-15-15-15 repetitions), with cuffs applied at pressures corresponding to 40% and 60% of the minimum arterial occlusion pressure (AOP) needed to completely collapse the femoral arteries. During each of these conditions (40% and 60% AOP), physiological measures of near-infrared spectroscopy (NIRS) and EMG amplitude (EMG AMP) were collected from the dominant or nondominant vastus lateralis. After each set, ratings of perceived exertion (RPE) were collected, whereas only at baseline and at the end of the bout, mean arterial pressure (MAP) was assessed. Separate mixed-factorial ANOVA models were used to examine mean differences in the change in EMG AMP and NIRS parameters during each set. The absolute RPE and MAP values were also examined with separate ANOVAs. A P value ≤0.05 was considered statistically significant. RESULTS: Regardless of sex or cuff pressure, the change in EMG AMP was lower in set 1 (14.8%) compared with the remaining sets (22.6%-27.0%). The 40% AOP condition elicited the greatest changes in oxy[heme] and deoxy[heme], while also providing lower RPEs. For MAP, there was an effect for time such that MAP increased from preexercise (87.5 ± 4.3 mm Hg) to postexercise (104.5 ± 4.1 mm Hg). CONCLUSIONS: The major findings suggested that the 40% AOP condition permitted the greatest amount of recovery during the interset rest. In addition, there did not seem to be any meaningful sex-related difference in this sample of young healthy adults.

The role of muscle mass in vascular remodeling: insights from a single-leg amputee model.

PURPOSE: Both muscle mass and physical activity are independent mechanisms that play a role in vascular remodeling, however, the direct impact of muscle mass on the structure and function of the vessels is not clear. The aim of the study was to determine the impact of muscle mass alteration on lower limbs arterial diameter, blood flow, shear rate and arterial stiffness. METHODS: Nine (33 ± 13 yrs) male individuals with a single-leg amputation were recruited. Vascular size (femoral artery diameter), hemodynamics (femoral artery blood flow and shear rate were measured at the level of the common femoral artery in both amputated (AL) and whole limbs (WL). Muscle mass of both limbs, including thigh for AL and thigh and leg for WL, was measured with a DXA system. RESULTS: AL muscle mass was reduced compared to the WL (3.2 ± 1.2 kg vs. 9.4 ± 2.1 kg; p = 0.001). Diameter of the femoral artery was reduced in the AL (0.5 ± 0.1 cm) in comparison to the WL (0.9 ± 0.2 cm, p = 0.001). However, femoral artery blood flow normalized for the muscle mass (AL = 81.5 ± 78.7ml min-1 kg-1,WL = 32.4 ± 18.3; p = 0.11), and blood shear rate (AL = 709.9 ± 371.4 s-1, WL = 526,9 ± 295,6; p = 0.374) were non different between limbs. A correlation was found only between muscle mass and femoral artery diameter (p = 0.003, R = 0.6561). CONCLUSION: The results of this study revealed that the massive muscle mass reduction caused by a leg amputation, but independent from the level of physical activity, is coupled by a dramatic arterial diameter decrease. Interestingly, hemodynamics and arterial stiffness do not seem to be impacted by these structural changes.

A Multiple Linear Regression Model for Carotid-to-Femoral Pulse Wave Velocity Estimation Based on Schrodinger Spectrum Characterization.

In this paper, a multiple linear regression model for estimating the Carotid-to-femoral pulse wave velocity (cf-PWV) from a single non-invasive peripheral pulse wave, namely blood pressure or photoplethysmography, is proposed. The training and testing datasets were extracted from in-silico, publicly available, pulse waves and hemodynamics data. The proposed model relies on a preprocessing and features extraction steps, which are performed using a semi-classical signal analysis (SCSA) method. The obtained results provide more evidence for the feasibility of machine learning and the SCSA method as a smart tool for the efficient assessment of the cf-PWV.

Characteristics of deep vein thrombosis in the critically ill COVID-19 patient - an observational cohort study with Doppler ultrasound measurements.

OBJECTIVE: COVID-19 is associated with an increased prevalence of deep venous thrombosis (DVT), mainly in the lower limbs. However, the characteristics and rheological conditions, which contribute to facilitating DVT occurrence have been poorly investigated. We aimed to report DVT characteristics, vein diameters and peak blood flow velocities (PBFV) in the common femoral veins (CFVs) of critically ill COVID-19 patients. PATIENTS AND METHODS: We conducted a prospective single-center cohort study in March-October 2020 including all consecutive mechanically ventilated COVID-19 adults. Doppler ultrasound of the lower limbs was performed systematically during the first week of hospitalization. In DVT-free patients, a second Doppler ultrasound was performed seven days later. Data are expressed as medians (interquartile ranges) or percentages. Comparisons were performed using Mann-Whiney and Wilcoxon signed-rank tests or Fischer's exact tests, as appropriate. RESULTS: Fifty-five patients [age, 63 years (56-74); female/male ratio, 0.62; body-mass index, 29 kg/m2 (26-33); hypertension, 47%; diabetes, 38%; ischemic heart disease, 11%] were included. DVT was diagnosed in 19 patients (35%) including in 5 femoral (9%), 2 popliteal (4%) and 12 below-the-knee sites (22%). CFV diameter was increased to 12.0 mm (11.0-15.0) (normal range, 9.1-12) and PBFV reduced to 11.9 cm/s (8.8-15.8) (normal range, 21.3-49.2) [right-side values]. In four patients who had ultrasound before intubation, CFV diameter increased from 12.5 mm (11.8-13.3) before to 14 mm (13.6-15.3) after intubation (p = 0.008). CONCLUSIONS: DVT in the CFV occurred in 9% of the critically ill COVID-19 patients with an overall 35%-DVT prevalence. Venous return difficulty evidenced by larger than normal CFV diameters and lower than normal PBFVs may have facilitated proximal DVT occurrence.

Repeated Passive Mobilization to Stimulate Vascular Function in Individuals of Advanced Age Who Are Chronically Bedridden: A Randomized Controlled Trial.

BACKGROUND: Vascular dysfunction and associated disorders are major side effects of chronic bed rest, yet passive mobilization as a potential treatment has only been theorized so far. This study investigated the effects of passive mobilization treatment on vascular function in older, chronically bedridden people. METHOD: The study sample was 45 chronically bedridden people of advanced age (mean age: 87 years; 56% female; mean bed rest: 4 years) randomly assigned to a treatment (n = 23) or a control group (CTRL, n = 22). The treatment group received passive mobilization twice daily (30 minutes, 5 times/wk) for 4 weeks. A kinesiologist performed passive mobilization by passive knee flexion/extension at 1 Hz in one leg (treated leg [T-leg] vs control leg [Ctrl-leg]). The CTRL group received routine treatment. The primary outcome was changes in peak blood flow (∆peak) as measured with the single passive leg movement test at the common femoral artery. RESULTS: ∆Peak was increased in both legs in the Treatment group (+90.9 mL/min, p < .001, in T-leg and +25.7 mL/min, p = .039 in Ctrl-leg). No difference in peak blood flow after routine treatment was found in the CTRL group. CONCLUSION: Improvement in vascular function after 4 weeks of passive mobilization was recorded in the treatment group. Passive mobilization may be advantageously included in standard clinical practice as an effective strategy to treat vascular dysfunction in persons with severely limited mobility.

Long-Term Passive Leg Stretch Improves Systemic Vascular Responsiveness as Much as Single-Leg Exercise Training.

PURPOSE: The current study compared the local and systemic vascular responsiveness after small muscle mass endurance training or passive stretching training (PST). METHODS: Thirty-six sex-matched healthy participants underwent 8-wk single-leg knee extension (SLKE) (n = 12) training or PST (n = 12), or no intervention (control, n = 12). Before and after the intervention, local and systemic vascular responsiveness was assessed by Doppler ultrasound at the femoral (local effect) and brachial artery (systemic effect) during single passive leg movement and brachial flow-mediated dilation (FMD) test, respectively. RESULTS: After training, delta femoral blood flow (representing the local vascular responsiveness) increased after SLKE and PST by +54 (7)% (effect size, 2.72; P < 0.001) and +20 (2)% (effect size, 2.43; P < 0.001), respectively, albeit with a greater extent in SLKE (post-SLKE vs post-PST: +56 [8]% [effect size, 2.92; P < 0.001]). Interestingly, the %FMD (standing for the systemic effect) increased after SLKE and PST by +12 (2)% (effect size, 0.68; P < 0.001) and +11 (1)% (effect size, 0.83; P < 0.001), respectively, without any between-groups difference (P > 0.05). No changes occurred in control. CONCLUSIONS: The present findings revealed that both active and passive training modalities induced similar improvements in the brachial artery dilatation capacity, whereas the former was more effective in improving femoral artery blood flow. Passive stretching could be used in people with limited mobility to improve vascular responsiveness both at the local and systemic level and in this latter case has similar effects as small muscle mass endurance training.

Fitness Level- and Sex-Related Differences in Macrovascular and Microvascular Responses during Reactive Hyperemia.

PURPOSE: Reactive hyperemia (RH) is widely used for the investigation of macrovascular (flow-mediated dilation, or FMD) and microvascular (near-infrared spectroscopy-vascular occlusion test, or NIRS-VOT) function. Mixed results have been reported on fitness level- and sex-related differences in FMD outcomes, and little is known about microvascular differences in untrained and chronically trained males and females. METHODS: Fifteen chronically trained (CT: 8 males, 7 females) and 16 untrained (UT: 8 males, 8 females) individuals participated in this study. Aerobic fitness (V˙O2max) was assessed during a cycling incremental exercise test to volitional exhaustion. FMD and NIRS-VOT were performed simultaneously on the lower limb investigating superficial femoral artery and vastus lateralis muscle, respectively. RESULTS: %FMD was not different between groups (CT males, 4.62 ± 1.42; CT females, 4.15 ± 2.23; UT males, 5.10 ± 2.53; CT females, 3.20 ± 1.67). Peak blood flow showed greater values in CT versus UT (P ≤ 0.0001) and males versus females (P = 0.032). RH blood flow area under the curve was greater in CT versus UT (P = 0.001). At the microvascular level, desaturation and reperfusion rates were faster in CT versus UT (P = 0.018 and P = 0.013) and males versus females (P = 0.011 and P = 0.005). V˙O2max was significantly correlated with reperfusion rate (P = 0.0005) but not with %FMD. CONCLUSIONS: Whereas NIRS-VOT outcomes identified fitness- and sex-related differences in vascular responses, %FMD did not. However, when RH-related outcomes from the FMD analysis were considered, fitness- and/or sex-related differences were detected. These data highlight the importance of integrating FMD and NIRS-VOT outcomes for a more comprehensive evaluation of vascular function.

Nonbone Marrow CD34+ Cells Are Crucial for Endothelial Repair of Injured Artery.

[Figure: see text].

The passive leg movement technique for assessing vascular function: the impact of baseline blood flow.

NEW FINDINGS: What is the central question of this study? The passive leg movement (PLM) assessment of vascular function utilizes the blood flow response in the common femoral artery (CFA): what is the impact of baseline CFA blood flow on the PLM response? What is the main finding and its importance? Although an attenuated PLM response is not an obligatory consequence of increased baseline CFA blood flow, increased blood flow through the deep femoral artery will diminish the response. Care should be taken to ensure that a genuine baseline leg blood flow is obtained prior to performing a PLM vascular function assessment. ABSTRACT: The passive leg movement (PLM) assessment of vascular function utilizes the blood flow response in the common femoral artery (CFA). This response is primarily driven by vasodilation of the microvasculature downstream from the deep (DFA) and, to a lesser extent, the superficial (SFA) femoral artery, which facilitate blood flow to the upper and lower leg, respectively. However, the impact of baseline CFA blood flow on the PLM response is unknown. Therefore, to manipulate baseline CFA blood flow, PLM was performed with and without upper and lower leg cutaneous heating in 10 healthy subjects, with blood flow (ultrasound Doppler) and blood pressure (finometer) assessed. Baseline blood flow was significantly increased in the CFA (∼97%), DFA (∼109%) and SFA (∼78%) by upper leg heating. This increase in baseline CFA blood flow significantly attenuated the PLM-induced total blood flow in the DFA (∼62%), which was reflected by a significant fall in blood flow in the CFA (∼49%), but not in the SFA. Conversely, lower leg heating increased blood flow in the CFA (∼68%) and SFA (∼160%), but not in the DFA. Interestingly, this increase in baseline CFA blood flow only significantly attenuated the PLM-induced total blood flow in the SFA (∼60%), and not in the CFA or DFA. Thus, although an attenuated PLM response is not an obligatory consequence of an increase in baseline CFA blood flow, an increase in baseline blood flow through the DFA will diminish the PLM response. Therefore, care should be taken to ensure that a genuine baseline leg blood flow is obtained prior to performance of a PLM vascular function assessment.

Comparison of transradial and transfemoral access for transcatheter arterial embolization of iatrogenic renal hemorrhage.

BACKGROUND: There are few reports of renal artery embolization (RAE) via transradial access (TRA) for renal hemorrhage, and none have compared outcomes of RAE via TRA and transfemoral access (TFA). The objective was to compare technical and clinical outcomes in patients undergoing RAE via TRA or TFA for iatrogenic renal hemorrhage. MATERIALS AND METHODS: This study included 45 RAE procedures (16 TRA and 29 TFA) for iatrogenic renal hemorrhage in 43 patients performed at a tertiary referral center between October 2018 and December 2020. Information regarding underlying diseases, coagulation status, angiographic and embolization procedure details, technical and clinical successes, and complications were retrospectively evaluated. RESULTS: There were no differences in demographics, underlying diseases, updated Charlson comorbidity scores, angiographic findings, and volume of contrast material between the TRA and TFA groups. By contrast, prothrombin time and international normalized ratio were significantly lower in the TRA than in the TFA group. Embolic materials differed significantly in the two groups. Procedure duration, fluoroscopy time, digital subtraction angiography number, and dose area product were slightly lower in the TRA than in the TFA group, but the differences were not statistically significant. Technical and clinical success rates in the TRA and TFA groups were 100% and 96.6%, and 100% and 96.6%, respectively. No patient in either group experienced procedure-related complications during a 4 week follow-up period. CONCLUSION: RAE via TRA in the management of iatrogenic renal hemorrhage was safe and feasible, with similar procedure duration and radiation exposure to RAE via TFA. TRA may be an acceptable alternative to TFA in these patients.

Prenatal Exercise and Cardiovascular Health (PEACH) Study: Impact on the Vascular System.

PURPOSE: Healthy pregnancy is typically associated with favorable vascular adaptations to both structure and function of the peripheral arteries. Exercise is independently associated with improvements in peripheral vascular health; however, the impact of exercise on prenatal adaptations is unclear. Therefore, we hypothesized that a structured aerobic exercise intervention between the second and third trimesters (TM2 and TM3, respectively) of pregnancy would augment the already-positive changes in vascular outcomes. METHODS: We recruited 59 inactive pregnant women (<20 wk of gestation) and randomized them into control (standard care; n = 28) or exercise (moderate-intensity aerobic exercise, 3-4 d·wk-1, 25-40 min, 14 ± 1 wk; n = 31) conditions. Before and after the intervention, all women completed the comprehensive peripheral vascular assessment, which included blood markers of vascular health, carotid distensibility metrics, measures of arterial stiffness (pulse wave velocity), and [superficial] femoral artery reactivity during cold pressor test. RESULTS: Carotid artery diameter increased from 6.5 to 6.9 mm (P < 0.001), and strain (%) decreased from 9.9% to 8.4% (P < 0.001). Carotid artery blood flow, compliance and distensibility coefficients, stiffness (ß), distensibility (1/ß), and elastic modulus were not different across gestation. Pulse wave velocity was not different across gestation. Superficial femoral artery diameter was increased from 5.4 to 5.6 mm (P = 0.004), whereas blood flow, conductance, and resistance at rest and during the cold pressor test were not different across gestation. None of our measures of vascular health were impacted by exercise. CONCLUSIONS: We did not observe an impact of aerobic exercise on altering the changes across pregnancy in blood vessel health. However, the present study was conducted in women who were overall at low risk for developing gestational hypertension and should be interpreted with caution. Future work in high-risk women is needed.

The impact of repeated, local heating-induced increases in blood flow on lower limb endothelial function in young, healthy females.

PURPOSE: The purpose of the present study was to examine the effect of repeated, single leg heating on lower limb endothelial function. METHODS: Macrovascular function was assessed with superficial femoral artery (SFA) reactive hyperemia flow-mediated dilation (RH-FMD) and sustained stimulus FMD (SS-FMD). Calf microvascular function was assessed as the peak and area under the curve of SFA reactive hyperemia (RH). Participants (n = 13 females, 23 ± 2 yrs) had one leg randomized to the single leg heating intervention (EXP; other leg: control (CON)). The EXP leg underwent 8 weeks of single leg heating via immersion in 42.5 â„ƒ water for five 35-min sessions/week. At weeks 0, 2, 4, 6, and 8, SFA RH-FMD, SS-FMD (shear stress increased via plantar flexion exercise), and SFA RH flow were measured. RESULTS: None of the variables changed with repeated, single leg heating (interaction week*limb RH-FMD: p = 0.076; SS-FMD: p = 0.958; RH flow p = 0.955). Covariation for the shear stress stimulus did not alter the FMD results. CONCLUSION: Eight weeks of single leg heating did not change SFA endothelial or calf microvascular function. These results are in contrast with previous findings that limb heating improves upper limb endothelial function.

Estimating pulse wave velocity from the radial pressure wave using machine learning algorithms.

One of the European gold standard measurement of vascular ageing, a risk factor for cardiovascular disease, is the carotid-femoral pulse wave velocity (cfPWV), which requires an experienced operator to measure pulse waves at two sites. In this work, two machine learning pipelines were proposed to estimate cfPWV from the peripheral pulse wave measured at a single site, the radial pressure wave measured by applanation tonometry. The study populations were the Twins UK cohort containing 3,082 subjects aged from 18 to 110 years, and a database containing 4,374 virtual subjects aged from 25 to 75 years. The first pipeline uses Gaussian process regression to estimate cfPWV from features extracted from the radial pressure wave using pulse wave analysis. The mean difference and upper and lower limits of agreement (LOA) of the estimation on the 924 hold-out test subjects from the Twins UK cohort were 0.2 m/s, and 3.75 m/s & -3.34 m/s, respectively. The second pipeline uses a recurrent neural network (RNN) to estimate cfPWV from the entire radial pressure wave. The mean difference and upper and lower LOA of the estimation on the 924 hold-out test subjects from the Twins UK cohort were 0.05 m/s, and 3.21 m/s & -3.11m/s, respectively. The percentage error of the RNN estimates on the virtual subjects increased by less than 2% when adding 20% of random noise to the pressure waveform. These results show the possibility of assessing the vascular ageing using a single peripheral pulse wave (e.g. the radial pressure wave), instead of cfPWV. The proposed code for the machine learning pipelines is available from the following online depository (https://github.com/WeiweiJin/Estimate-Cardiovascular-Risk-from-Pulse-Wave-Signal).

Influence of muscular contraction on vascular conductance during exercise above versus below critical power.

We tested the hypothesis that limb vascular conductance (LVC) would increase during the immediate recovery phase of dynamic exercise above, but not below, critical power (CP) indicating a threshold for muscular contraction-induced impedance of limb blood flow (LBF). CP (115 ± 26 W) was determined in 7 men and 7 women who subsequently performed ∼5 min of near-supine cycling exercise both below and above CP. LVC demonstrated a greater increase during immediate recovery and remained significantly higher following exercise above, compared to below, CP (all p < 0.001). Power output was associated with the immediate increases in LVC following exercise above, but not below, CP (p < 0.001; r = 0.85). Additionally, variance in percent LBF impedance was significantly lower above (CV: 10.7 %), compared to below (CV: 53.2 %), CP (p < 0.01). CP appears to represent a threshold above which the characteristics of LBF impedance by muscular contraction become intensity-dependent. These data suggest a critical level of LBF impedance relative to contraction intensity exists and, once attained, may promote the progressive metabolic and neuromuscular responses known to occur above CP.