Changes In Brachial Artery Diameter Research Articles

BRACHIAL, FEMORAL, AND SKIN HAEMODYNAMIC RESPONSES TO WALKING IN HOT CONDITIONS: COMPARISON BETWEEN MALES AND FEMALES

INTRODUCTION & AIMS Heat exposure induces acute changes in arterial function, but sex differences have not been fully addressed. METHODS Participants walked (5km/h; 2% incline) in a climate chamber (42°C;50%RH) for 120mins. Cutaneous microvascular function (laser doppler flowmetry), conduit artery haemodynamics (Doppler ultrasound) and core temperature were measured at baseline, and every 30min. RESULTS 14♂ and 15♀ completed 120min. At baseline, differences in core temperature (Tc) between males and females were not significant (37.2±0.1 vs 37.0±0.1°C; P=0.06). Across all 5 timepoints, females exhibited larger Tc than males (P=0.019). At baseline, males had larger brachial (3.89±0.11 vs 3.13±0.09mm, P<0.001) and femoral (6.22±0.16 vs 5.29±0.14mm, P=0.001) diameters than females. A significant interaction (P=0.047) indicated that brachial diameter increased more in response to heat exertion than in males, whereas no sex difference was apparent in femoral diameter change. Males and females had similar baseline brachial flows (♂80.1±11.2 vs ♀57.0±7.09ml/min, P=0.087), but males had larger baseline femoral flows (♂263.0±23.9 vs ♀151.5±18.6 ml/min, P=0.010). No sex differences were apparent in the terms of the increases in brachial or femoral flows. Finally, at baseline males and females had similar skin blood flux (♂22.6±2.7 vs ♀18.3±2.9PU), but males demonstrated larger increases during heat exertion (P=0.029). CONCLUSIONS Males exhibit larger baseline artery diameters and flows in vessel beds feeding active (femoral) and inactive (brachial) limbs. In response to heat exertion, men and women exhibit similar increases in conduit diameter and flow to active muscle beds (femoral responses). In the inactive forearms, which reflect thermoregulatory responses, females had larger brachial artery diameter changes, but blood flow responses were similar between the sexes and men demonstrated larger increases in skin perfusion. These data indicate that responses to heat exertion differ in the upper and lower limbs, with sex-differences apparent in each of these territories, and at distinct levels of the arterial hierarchy.

Brachial artery flow-mediated dilation during incremental handgrip exercise is not impacted by sex or female sex hormones

Sex differences exist in reactive hyperemia flow-mediated dilation (RH-FMD), with males demonstrating larger RH-FMD responses than naturally menstruating females and females using oral contraception (OC). This difference is thought to be partly attributed to sex hormones. Among females, some studies demonstrate lower RH-FMD in females using OC relative to naturally menstruating females. To date, non-invasive assessments of endothelial function in males, naturally cycling females and females using OC have only been completed using RH-FMD. Notably, due to differences in the shear stimulus during sustained shear-induced FMD (SS-FMD) versus the transient pattern observed with RH-FMD, SS-FMD may provide distinct insight into endothelial dysfunction undetected with RH-FMD. Therefore, we hypothesized that the SS-FMD responses to incremental handgrip (IHG) exercise would be greatest in males, and that females using OC would have the smallest increase in SS-FMD compared to males and naturally menstruating females. The IHG protocol consisted of 3-minute stages of rhythmic handgrip exercise at 15, 30, and 45% of an individual’s maximal voluntary contraction (MVC) force, with no rest period between MVC transitions. Brachial artery diameter and blood velocity were measured simultaneously via duplex Doppler ultrasound in 10 males (26±4 [mean±SD] years), 11 naturally menstruating females (25±4 years), and 9 females using OC (27±5 years) during IHG. Females were tested in the mid-luteal (ML) and active (high hormone) OC phases. SS-FMD and shear rate were analyzed using linear mixed model analyses. MVC was greater in males relative to both groups of females (males: 40±6, ML: 28±8, OC: 26±6 kg; One-way ANOVA: post-hocs P≤0.001). Brachial artery shear rate was not different between males, ML females or females using OC throughout exercise (group-by-stage interaction: P=0.975). Consequently, the brachial artery dilated by 1.3±1.5, 0.1±2.1, and 1.2±3.6 % at 15% MVC, 4.0±3.1, 2.7±3.3, and 4.1±4.8 % at 30% MVC, and 9.1±4.9, 7.3±5.4, and 7.6±5.9 % at 45% MVC, in males, ML females, and females using OC, respectively (all P>0.05). Furthermore, the slopes of the relationship between the change in brachial artery diameter and shear rate was similar between the three groups (Males: 0.0004±0.0002, ML: 0.0003±0.0002, OC: 0.0003±0.0002 Δmm/Δ1·s -1 ; One-way ANOVA: P=0.564). Taken together, these data indicate that endothelial function in response to sustained elevations in shear stress are not impacted by biological sex or OC use. Supported by the Natural Sciences and Engineering Research Council of Canada, and IEEM indirect funds. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Median Nerves' Electrical Activation Reduces Ipsilateral Brachial Arteries' Blood Flow and Diameter.

Our main objective in this study was to determine whether there is a difference between ipsilateral and contralateral brachial arteries' flow parameters in response to median nerves' electrical activation. The study was conducted in healthy and active subjects. The arterial diameter and flow were measured using the probe from the brachial artery. Then, the median nerve was stimulated for 5 seconds via the bipolar stimulus electrode. Arterial diameter and flow were measured once more with the Doppler transducer, which kept going to monitor continuously just after the fifth stimulus. After a week, the same subjects are invited for the purpose of measuring the contralateral brachial arteries' vasomotor response to the same stimulus. Before electrical stimulation, the median flow rate was 72.15 ml/min; after stimulation, the median flow rate was 39.20 ml/min. The drop in flow after stimulation was statistically significant (P < 0.001). While the median value of brachial artery vessel diameter before median nerve stimulation in the entire study group was 3.50 mm, the median value of vessel diameter after stimulation was 2.90 mm. After stimulation, the median nerve diameter narrowed statistically significantly (P < 0.001). As for the contralateral brachial in response to the right median nerves' activation, no significant flow or diameter change was found (P = 0.600, P = 0.495, respectively). We discovered that electrical stimulation of the median nerve caused significant changes in ipsilateral brachial artery blood flow and diameter in healthy volunteers. The same stimulation does not result in flow parameter changes in the contralateral brachial artery.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension.

Background: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. Methods: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. Results: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: −4.0; −2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. Conclusion: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

Effect of Acute Isometric Handgrip Exercise on Vascular Function in Children with Congenital Heart Disease

ObjectiveThe reactivity of conduit vessels such as the brachial artery is important in influencing arterial diameter, and subsequently, blood flow. Flow‐mediated dilation (FMD) measures vessel reactivity. The increase in shear stimuli from transient arterial occlusion enhances arterial diameter in an endothelial‐dependent manner, and this is thought to be impaired in individuals with congenital heart disease (CHD). Isometric handgrip (IHG) exercise is a proposed intervention to improve vessel reactivity by optimizing the shear stimuli to provoke changes in arterial diameter. Indeed, IHG training has been found to improve FMD in healthy adults and children. Whether IHG training improves endothelial dysfunction in CHD remains unknown. Improving vessel reactivity in the young becomes increasingly important in optimizing vascular health into adulthood. The effects of acute IHG exercise on the brachial artery were examined in children with CHD.HypothesisWe tested the hypothesis that acute IHG exercise would increase FMD in children with CHD.MethodsFour subjects with CHD (mean, 13 ± 1 year, 3 female) completed a single session of 4 × 2 mins of acute IHG (30% maximum voluntary contraction using the right hand) with 1‐min rest intervals between bouts. Before and after IHG exercise, the right brachial artery was imaged with Duplex ultrasound using a 1‐min baseline, 5 mins of forearm circulatory occlusion, followed by 3 mins of cuff deflation. Blood pressure and heart rate were measured continuously.ResultsPre‐FMD (baseline) mean arterial pressure (pre: 102 ± 17 mmHg vs. post: 110 ± 16 mmHg, p = 0.496) and heart rate (pre: 75 ± 13 bpm vs. post: 66 ± 5 bpm, p = 0.253) were not different. Baseline brachial artery diameter increased following acute IHG in 3 of 4 subjects (pre: 3.11 ± 0.45 mm vs. post: 3.23 ± 0.39 mm, Cohen’s d = 0.3). Peak shear rate was greater post‐IHG in 3 of 4 subjects (pre: 995 ± 346 sec‐1vs. post: 1158 ± 501 sec‐1, Cohen’s d = 0.4). FMD% (4.7% vs. 6.3% and 8.2% vs. 10.5%) and FMD% normalized to shear rate area under the curve (AUC) ratio (2.2E‐5 vs. 7.4E‐5 a.u. and 3.1E‐5 vs. 4.3E‐5 a.u., Cohen’s d = 2.0) increased post‐IHG in 2 of 4 subjects. When brachial artery diameter increased, peak shear rate, FMD%, and FMD% normalized to shear rate AUC improved post‐IHG in 2/3 subjects whereas subject four showed a decrease in brachial artery diameter, FMD% and FMD% normalized to shear rate AUC, with the exception of peak shear rate post‐IHG.ConclusionFavorable changes in brachial artery diameter, peak shear rate, FMD% and FMD% normalized to shear rate AUC following acute IHG may be a promising intervention for improving vascular tone and endothelial function in children with CHD.

STUDY OF VASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract. Currently, inflammatory bowel disease (IBD) is the most complex and not fully resolved problem in modern gastroenterology. IBD, with its two main subtypes, Crohn's disease (CD) and ulcerative colitis (UC), is a complex multifactorial pathology caused by external and internal factors, including host genetics, the immune system, environmental factors, and the gut microbiome. The possible involvement of endothelial dysfunction is also discussed. There is evidence that in diseases characterized by chronic systemic inflammation, it affects the properties of the arteries and causes both endothelial dysfunction and changes in arterial stiffness. The aim is to study the functional state of the vascular endothelium in patients with inflammatory bowel diseases. Material and methods. A total of 69 patients with IBD aged 18 to 70 years (44.0 ± 1.4 years) were examined. All patients were divided into 2 groups depending on the nosology. 1st group consisted of 45 patients with UC, among them 23 women (51.1 %) and 22 men (48.9 %), 2nd group – 24 patients with HC, of which 14 women (58.3 %) and 10 men (41.7 %). To assess endothelial function, the method for determining endothelium-dependent vasodilation of the brachial artery (BA) in a test with reactive hyperemia was used to assess the change in BA diameter (dPA), a ATL PHILIPS HDI 5000 SONOS CT ultrasound machine with a 7.5 MHz linear transducer was used. The endothelial function index was calculated as the difference between dPA after decompression and the initial value, expressed as a percentage. The content of a soluble vascular cell adhesion molecule 1 (VCAM-1) was determined in blood serum by an enzyme immunoassay using a test system («Bender MedSystems GmbH», Austria) using an enzyme immunoassay analyzer «Stat Fax 303 Plus» («Awareness Technology Inc.», USA). The number of desquamated endothelial cells in the peripheral blood was determined by the method of J. Hladovec. Results. In the study of endothelium-dependent vasodilation (EDVD) PA in a test with reactive hyperemia, dysfunctions of the vascular endothelium were found in 75.4 % of the examined patients. Changes in vascular endothelial function were found in 82.3 % of patients with UC and 62.5 % with CC, mainly due to endothelial dysfunction (ED). Significant differences were found between the indicators of the average increase in dPA in the test with reactive hyperemia with decreased endothelial function (DEF) and normal endothelial function (NEF), as well as with DEF and ED in patients with severe UC. ED was observed 5.2 times more often than NEF (c2 = 56.8; p &lt; 0.001) and 2.6 times more often than PFE (c2 = 31.5; p &lt; 0.001). With moderate severity of the disease, DEF and ED occurred with the same frequency and 2.2 times higher than the number of patients with NEF (c2 = 11.3; p = 0.0008), changes in endothelium-dependent vasodilation were accompanied by a significant increase in the VCAM-1 level in serum of all IBD patients, but the highest expression of VCAM-1 was observed in UC. At the same time, the concentration of VCAM-1 was inversely correlated with endothelium-dependent vasodilation of BA (r = - 0.54, p &lt; 0.01), which is confirmed by the quantitative characteristics of the level of VCAM-1 in various states of the endothelium. The study of the content of circulating desquamated endothelial cells in the peripheral blood made it possible to establish an increase in their number by 5 times with ED – up to (15.5 ± 4.8) × 104/L (p &lt; 0.05), 2 times with DEF – up to (5.7 ± 0.3) × 104/L (p &lt; 0.001) versus (3.1 ± 0.4) × 104/L in the control group. An inverse correlation was found between the number of desquamated endothelial cells and endothelium-dependent BA vasodilation (r = - 0.59, p &lt; 0.01). Conclusions. The results of a comprehensive study of the functional state of the vascular endothelium indicate that the course of IBD is accompanied by a syndrome of endothelial dysfunction (with a predominance of DE), which is characterized by a decrease in endothelium-dependent vasodilation of BA, an increase in the level of VCAM-1 and the content of circulating desquamated endothelial cells in the blood. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, endothelial dysfunction.

Age- and sex-related profiles for macro, macro/micro and microvascular reactivity indexes: Association between indexes and normative data from 2609 healthy subjects (3-85 years).

Vascular reactivity (VR), defined as blood vessels’ capability to actively modify the diameter and flow resistances can be non-invasively assessed analyzing vascular response to forearm occlusion. Several VR indexes can be quantified: (i) ´microvascular´, which consider variables that depend almost exclusively on changes in distal resistances, (ii)´ macrovascular´, that evaluate the changes in brachial artery (BA) diameter, adjusting for blood flow stimulus, and (iii) ´macro/micro´, whose values depend on the micro and macrovascular response without discriminating each one´s contribution. VR indexes could not be associated. Many VR indexes have been used without availability of adequate normative data (reference intervals, RIs). Aims: (1) to evaluate macro, macro/micro and micro VR indexes obtained in a cohort of healthy children, adolescents and adults, (2) to evaluate the association between VR indexes, (3) to determine the need for age and/or sex-specific RIs, and (4) to define RIs for VR indexes. Methods: Ultrasound (B-mode/Doppler) and automatic computerized analysis were used to assess BA diameter, blood flow velocity and distal resistances, at rest and in conditions of decreased and increased blood flow. Macro, macro/micro and micro VR indexes were quantified (n = 3619). RIs-subgroups were defined according to European Reference Values for Arterial Measurements Collaboration Group (n = 1688, 3–84 years) and HUNT3-Fitness Study Group (n = 2609, 3–85 years) criteria. Mean value and standard deviation equations were obtained for VR indexes. The need for age or sex-specific RIs was analyzed. Percentile curves were defined and data were compared with those obtained in other populations. Conclusion: Macro and macro/micro VR indexes showed no association (or it was very weak) with microvascular indexes. Age- and sex-related profiles and RIs for macro, macro/micro and micro VR indexes were defined in a large population of healthy subjects (3–85 y). Equations for mean, standard deviation and percentiles values (year-to-year) were included in text and spreadsheet formats.

Natural Fluctuations in Progesterone Do Not Impact Vascular Function in Healthy Premenopausal Women

Endogenous sex hormone concentrations vary across the menstrual cycle of naturally menstruating premenopausal women and may elicit concomitant changes in vascular function. Specifically, estrogen (E2) may enhance vascular function, partially by increasing nitric oxide bioavailability. In contrast, the influence of progesterone (P4) on vascular function remains unclear, with some data suggesting it increases nitric oxide bioavailability and other data suggesting it antagonizes the dilatory effects of E2. The objective of the study was to elucidate potential effects of P4 on the macrovascular function of healthy premenopausal women in the presence of relatively lower E2 concentrations. It was hypothesized that measures of macrovascular function would be similar between the early follicular (EF) and early luteal (EL) phases of healthy premenopausal women, despite a significant increase in the progesterone-to-estrogen ratio from the EF to the EL phase. Sex hormones and vascular function were measured in ten healthy premenopausal women (22±2 y) during the EF phase (within 5 days of the onset of menstruation) and the EL phase (4±2 days post-ovulation) of a single menstrual cycle. Serum concentrations of E2 and P4 were analyzed using enzyme-linked immunosorbent assays. Independent concentrations of E2 and P4 were calculated, as well as P4:E2. Macrovascular function was assessed via brachial artery flow-mediated dilation (FMD). %FMD was calculated as the percent change in brachial artery diameter following an ischemic stimulus. Data were compared between phases with paired t-tests. Serum concentrations of E2 and P4 increased from the EF to the EL phase (91.8±34.5 vs. 120.9±32.6 pg/mL, p=0.01 and 1.4±0.6 vs. 5.1±3.6 ng/mL, p=0.01, respectively). The P4:E2 increased significantly from the EF to the EL phase as a result of the P4 surge in the EL phase (15.5±4.8 vs. 42.9±30.5, p=0.02). %FMD did not differ between the EF and EL phases (9.6±4.4 vs. 9.5±3.5 %, p=0.97). In conclusion, the macrovascular function of healthy premenopausal women is similar between the EF and EL phases despite significant increases in the P4:E2. Findings may suggest that P4 does not play an antagonist role on E2 and may have a synergistic effect on increasing %FMD among decreased concentrations of E2.

Impact of Family History of Hypertension on Racial Differences in Flow‐Mediated Dilation and Reactive Hyperemia

The prevalence of hypertension and cardiovascular disease is highest in non-Hispanic black (BK) individuals. This has led to a number of studies investigating potential racial differences in vascular function, assessed as flow-mediated dilation (FMD, macrovascular function) and reactive hyperemia (RH, microvascular function). These studies suggest that otherwise healthy BK individuals may have reduced vasodilator responses, compared to white (WH) individuals. However, it is notable that these studies did not consider the participants' family history of hypertension (FHH), which is important because studies have shown that individuals with a positive (+) FHH exhibit blunted vasodilator function compared to those with no FHH (-FHH). Hence, whether the higher prevalence of +FHH among BK individuals contributed to the previously reported differences in FMD and RH between BK and WH individuals is unknown. Thus, we aimed to investigate the impact of FHH on FMD and RH in BK and WH males. We hypothesized that FMD and RH would be attenuated in BK compared to WH males, and further, a +FHH would reduce FMD and RH compared to a -FHH in both groups. We studied 17 young healthy BK (+FHH: n = 9) and WH males (+FHH: n = 9). Heart rate (ECG) and brachial artery diameter and blood velocity (duplex Doppler Ultrasound) were continuously measured while subjects laid supine. Baseline measures were recorded for 2 min, following which a cuff placed around the forearm was rapidly inflated to 220 mmHg for 5 min. All measurements were recorded for 30 s prior to and 3 min after cuff release. FMD was quantified as a percent change in brachial artery diameter from baseline to peak diameter after cuff release. The impact of shear rate on FMD was controlled for statistically using an ANCOVA. RH was quantified as peak blood velocity and hyperemic blood velocity area under the curve (AUC) to 60s after cuff release. Baseline brachial artery diameter and blood velocity were not different between groups (P > 0.05 for all comparisons). FMD was significantly blunted in BK (4.12 ± 0.64%, Mean ± SE) compared to WH males (6.00 ± 0.49%; P = 0.025), and remained significantly blunted after controlling for impact of shear rate on FMD (BK: 4.19 ± 0.58% vs. WH: 5.93 ± 0.58%; P = 0.046). There was no effect of FHH on FMD in either race (interaction and main effect of FHH P > 0.05). Likewise, RH was significantly blunted in BK compared to WH males when quantified as peak blood velocity (BK: 58 ± 3 cm.s-1 vs. WH: 70 ± 4 cm.s-1, P = 0.025), as well as hyperemic blood velocity AUC to 60s (BK: 1419 ± 85 a.u. vs. WH: 1738 ± 123 a.u., P = 0.041), with no effect of FHH in either race (interaction and main effect of FHH P > 0.05 for both measures). These preliminary findings suggest that young healthy BK males exhibit attenuated FMD and RH compared to their WH counterparts; an effect that appears to be independent of FHH.

Brachial Artery “Low-Flow Mediated Constriction” Is Associated with Myocardial Perfusion Defect Severity and Mediated by an Altered Flow Pattern during Occlusion

Introduction: The relationship between low flow-mediated constriction (LFMC), a new proposed measure of endothelial function, with cardiovascular disease severity and its hypothesized stimulus, that is, low flow, has not been comprehensively evaluated. The study evaluated association between change in brachial artery diameter during constriction with severity of myocardial perfusion defect (PD) and alterations in different components of flow profile. Methods: Brachial artery responses to occlusion were assessed in 91 patients and 30 healthy subjects. Change in anterograde and retrograde blood flow velocities (delta anterograde blood flow velocity and retrograde blood flow velocity), anterograde shear rate and retrograde shear rate (delta ASR and RSR, respectively), and oscillatory shear index (delta) during forearm occlusion at 50 mm Hg above systolic pressure, from baseline was calculated. Myocardial perfusion was evaluated in patients using exercise single positron emission computed tomography and % myocardial PD was calculated from summed stress score. Results: LFMC emerged as independent predictor of defect severity after correcting for age and gender (p = 0.014). Sixty-seven patients (73.6%) and 15 healthy subjects (50%) showed constriction during occlusion. In stepwise backward regression analysis, RSR contributed 35.5% and ASR contributed 20.1% of the total 63.9% variability in artery diameter during occlusion. Conclusion: The results suggest that LFMC is independently associated with myocardial perfusion severity and is “mediated” by an altered flow profile during occlusion.

Прогнозирование состояния пациенток с преэклампсией на основании показателей эндотелийзависимой вазодилатации

Aim: to determine prognostic criteria of severe preeclampsia based on the assessment of endothelium-dependent (ED) flow-mediated dilation (FMD) of the brachial artery (BA). Patients and Methods: 97 pregnant women (&gt;28 weeks of pregnancy) with moderate preeclampsia were enrolled. These women were retrospectively divided into two groups. Group 1 included 42 pregnant women (mean age 30.0±0.5 years) in whom the severity of preeclampsia increased after treatment. Group 2 included 55 pregnant women (mean age 31.0±0.7 years) whose severity of preeclampsia did not increase after treatment. Group 3 (control group) included 20 women with a healthy pregnancy. ED FMD of BA was assessed by vascular ultrasound using a reactive hyperemia test. In addition, BA diameter and peak systolic velocity (PSV) 15 sec and 1 min after cuff deflation were measured. These measurements were performed at enrollment and after one week (or in feeling worse). Results: healthy pregnancy was characterized by a gradual increase in BA diameter in response to cuff inflation (by 15.7% and 23.9% after 15 sec and 1 min, respectively, at baseline and by 17.8% and 21.3% after 15 sec and 1 min, respectively, after one week). In pregnant women with preeclampsia, baseline changes in BA diameter were less significant. Meanwhile, after one week, a reduction in BA diameter was reported in group 1, and close-to-normal BA diameter was reported in group 2. In group 3, BA PSV increased by 5.2% and 16% in 15 sec and 1 min, respectively, after cuff inflation. In pregnant women with preeclampsia, BA PSV, in contrast, was reduced (more significant after 1 min). Conclusion: increased BA diameter and PSV by less than 10% 15 sec and 1 min after cuff inflation indicate endothelial dysfunction. A negative pattern of changes in these parameters suggests an unfavorable course of preeclampsia and its transition to severe disease. KEYWORDS: preeclampsia, endothelial dysfunction, vasodilation, brachial artery, peak systolic velocity, prognosis. FOR CITATION: Shavaeva R.Kh., Murashko A.V., Zuev V.M. et al. Predicting preeclampsia course based on endothelium-dependent dilation. Russian Journal of Woman and Child Health. 2021;4(4):317–321 (in Russ.). DOI: 10.32364/2618-8430-2021-4-4-317-321.

Rolling massage acutely improves skeletal muscle oxygenation and parameters associated with microvascular reactivity: The first evidence-based study

Although it has been claimed that rolling massage (RM), may lead to improvements in skeletal muscle oxygenation, metabolism, blood flow, and vascular function, scientific evidence has not yet been provided. Thus, the current study investigated the effects of 30 s and 2 min of RM on forearm muscle oxygenation, parameters associated with oxidative metabolism, and microvascular reactivity as well as brachial artery endothelial function. Forearm skeletal muscle parameters were assessed in 12 healthy young men (26 ± 6 yrs) using near-infrared spectroscopy (NIRS) combined with a 5-min vascular occlusion test. Additionally, brachial artery endothelial function was simultaneously assessed by measuring the relative change in brachial artery diameter normalized to the hyperemic blood flow (Normalized %FMD). These measurements were performed before and after the RM interventions performed on the anterior forearm muscles. Forearm muscle oxygenation increased after 30 s of RM (62 ± 7 to 71 ± 11%; p = 0.02) while there was no change from baseline to post-intervention after 2 min of RM. No change was observed for oxidative metabolism, however, the significant main effect (p = 0.02) for NIRS-derived reperfusion slope (%·s−1) indicated that microvascular function improved after both 30 s (2.30 ± 0.5 to 2.61 ± 0.70%·s−1) and 2 min of RM (2.33 ± 0.4 to 2.60 ± 0.85%·s−1). The lack of significant effects of RM on Normalized %FMD suggest that the RM did not acutely improve brachial artery endothelial function. These findings provide, for the first time, evidence that RM improves skeletal muscle oxygenation and parameters associated with microvascular reactivity. Additionally, RM increased brachial artery blood flow, but not upstream brachial artery endothelial function.

Acute Systemic Rho‐kinase Inhibition Reduces Blood Pressure and Influences Peripheral Vascular Tone in Healthy Older Adults

Aging is the primary risk factor for cardiovascular disease (CVD), and Rho‐kinase has emerged as an important contributor to the pathogenesis of CVD in preclinical and clinical studies. Therefore, we tested the hypothesis that acute, systemic Rho‐kinase inhibition would improve measures of CVD risk in older adults. We studied healthy young (YA; 25 ± 1 yrs; 6M/6F) and older adults (OA; 65 ± 1 yrs; 6M/7F) under control conditions (CON, intravenous saline) and during inhibition of Rho‐kinase via intravenous fasudil administration (60 mg) in a double‐blind, randomized, crossover design. In separate visits to the laboratory, saline and fasudil were infused over the course of 1 h, after which we measured blood pressure, carotid‐femoral pulse wave velocity (cfPWV; index of arterial stiffness), and central augmentation index (AIx; SphygmoCor XCEL). In a subset of participants (YA: 5M/5F; OA: 6M/3F), we assessed reactive hyperemia (RH) and flow‐mediated dilation (FMD) to evaluate microvascular function and conduit artery endothelial function, respectively. We measured brachial artery diameter and mean blood velocity (MBV; Doppler ultrasound) to calculate forearm vascular conductance (FVC; forearm blood flow/mean arterial pressure · 100). FMD was quantified as the percent change in brachial artery diameter following 5 min of forearm ischemia. Shear rate (8 · MBV/diameter) was expressed as area under the curve (SRAUC) from cuff release to peak diameter to quantify the stimulus for FMD. In OA, fasudil reduced systolic (SBP, 127 ± 4 vs. CON: 134 ± 4 mmHg, P &lt; 0.05), diastolic (DBP, 76 ± 2 vs. CON: 79 ± 1 mmHg, P &lt; 0.05), and mean arterial pressure (MAP, 93 ± 2 vs. CON: 97 ± 2 mmHg, P &lt; 0.05), and BP remained lower 1 and 2 h postinfusion. Although fasudil initially reduced SBP (114 ± 2 vs. CON: 119 ± 2 mmHg, P &lt; 0.05), DBP (68 ± 2 vs. CON: 72 ± 2 mmHg, P &lt; 0.05), and MAP (84 ± 2 vs. CON: 88 ± 2 mmHg, P &lt; 0.05) in YA, BP returned to control levels and was not different from CON at 1 or 2 h post‐infusion. Fasudil lowered cfPWV in OA (7.6 ± 0.4 vs. CON: 7.8 ± 0.4 m/s, P &lt; 0.05) and tended to lower cfPWV in YA (5.2 ± 0.2 vs. CON: 5.4 ± 0.2 m/s, P = 0.07). However, AIx was unchanged by the fasudil treatment in both OA (27 ± 2 vs. CON: 31 ± 2%, P = NS) and YA (−2 ± 2 vs. CON: −5 ± 5%, P = NS). Baseline brachial diameter increased with fasudil in OA (3.29 ± 0.23 vs. CON: 3.16 ± 0.20 mm, P &lt; 0.05), whereas fasudil had no effect on baseline diameter in YA (3.19 ± 0.19 vs. CON: 3.16 ± 0.17 mm, P = NS). Similarly, resting FVC was elevated under fasudil conditions in OA (36 ± 4 vs. CON: 25 ± 3 ml/min/100 mmHg, P &lt; 0.05), while FVC was unchanged with fasudil in YA (36 ± 9 vs. CON: 32 ± 5 ml/min/100 mmHg, P = NS). Following forearm ischemia, there was no effect of fasudil on peak blood flow (OA, 288 ± 30 vs. CON: 286 ± 31 ml/min, P = NS; YA, 346 ± 65 vs. CON: 346 ± 45 ml/min, P = NS) or on FMD (OA, 6.2 ± 1.1 vs. CON: 7.0 ± 1.1%, P = NS; YA, 6.5 ± 1.1 vs. CON: 7.9 ± 1.4%, P = NS). Fasudil did not affect SRAUC (OA, 29 ± 5 vs. CON: 29 ± 4 s−1 · 103, P = NS; YA, 32 ± 5 vs. CON: 36 ± 5 s−1 · 103) in either group. Collectively, these data suggest Rho‐kinase contributes to the age‐related elevation in blood pressure potentially via greater peripheral vasoconstrictor tone in healthy older adults.Support or Funding InformationHL119337

Improved Vascular Function Following 7 days of L‐Citrulline Administration in Heart Failure with Preserved Ejection Fraction

BackgroundThere is increasing evidence to support the presence of peripheral vascular dysfunction in patients with heart failure with preserved ejection fraction (HFpEF), which may be due, at least in part, to disease‐related changes in nitric oxide (NO) signaling. L‐Arginine (L‐Arg) is the sole substrate for NO synthesis, but is susceptible to intestinal and hepatic degradation via arginase when administered orally. L‐Citrulline (L‐Cit) is catabolized to L‐Arg at the tissue level and is not a substrate for arginase, and therefore enteral L‐Cit administration has emerged as an effective approach for increasing NO substrate bioavailability.PurposeThe present investigation sought to determine whether oral L‐Cit administration (6g/day for 7 days) would improve vascular function in patients with HFpEF.MethodsIn 13 patients NYHA Class II (n=9) and III (n=4) with HFpEF (2M/11F, 69±10y, EF: 66±7%), flow mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit artery and microvascular function, respectively. FMD was expressed as % change in brachial artery diameter (%FMD) and % change corrected for shear rate (%FMD/shear), and RH was calculated as area‐under‐the‐curve for brachial artery blood flow. Plasma L‐Cit and L‐Arg concentrations were assessed to confirm absorption and evaluate circulating NO substrate, and the ratio of L‐Arg to plasma asymmetric dimethylarginine (ADMA) was calculated as a biomarker of NO bioavailability.ResultsCompared to baseline, L‐Cit administration improved FMD (0d: 2.5 ± 0.5%, 7d: 4.7 ± 0.9%), FMD/shear (0d: 0.07 ± 0.02, 7d: 0.12 ± 0.01AU) and RH (0d: 450 ± 46ml, 7d: 574 ± 62ml). L‐Cit (0d: 42 ± 3μM/L, 7d: 370 ± 60 μM/L), L‐Arg (0d: 65 ± 8μM/L, 7d: 257 ± 25μM/L), and L‐Arg:ADMA (0d: 136 ± 14AU, 7d: 481 ± 50AU) all increased following L‐Cit administration.ConclusionsThis study has identified the efficacy of a 7d administration of L‐Cit to improve NO substrate bioavailability, the L‐Arg/ADMA ratio, and both conduit artery and microvascular function in patients with HFpEF. These results provide new insight into the mechanisms that govern peripheral vascular dysfunction in this patient group, and demonstrate a promising plasticity in the peripheral vasculature among patients with this chronic disease.Support or Funding InformationSupport or Funding Information: This project is funded in part by the National Institutes of Health (HL118313; D.W.W., R56AG057584; R.S.R., T32HL139451 R.S.R) and the U.S. Department of Veterans Affairs (I01RX001311; D.W.W., I01RX001697; R.S.R., I01RX002323; R.S.R., I21RX001433; R.S.R., I01RX000182; R.S.R.) and the American Heart Association (18POST33960192; K.B.).

Abstract P432: Racial Differences In Endothelial Function And Insulin Sensitivity

Racial disparities in health outcomes continue to be a significant public health concern and African Americans (AA) are disproportionately burdened by several risk factors for cardiovascular disease. Endothelial dysfunction has been shown to be a predictor of CVD and metabolic factors, including insulin resistance, are associated with endothelial dysfunction. Compared to EA, AA have impaired endothelial function and are more insulin resistant (less insulin sensitive). However, it remains unclear how insulin resistance may contribute to endothelial dysfunction in AA and EA. The purpose of the present study was to evaluate the relationship between insulin sensitivity and endothelial function in AA and EA. It was hypothesized that insulin sensitivity would be associated with endothelial function in both AA and EA. Skeletal muscle insulin sensitivity was measured by hyperinsulinemic-euglycemic glucose clamp technique in 112 lean, overweight, and obese AA and EA adults without diabetes. Insulin was infused at 120 mU/m 2 /min for 3 hours and an infusion of 20% dextrose was adjusted to maintain blood glucose at the fasting level. Insulin sensitivity (10 -4 .dL.kg -1 .min -1 /(μU/mL)) was defined as M/(G x ΔI), where M is steady state glucose infusion rate, G is steady state serum glucose concentration, and ΔI is the difference between basal and steady state serum insulin concentrations. M was adjusted for total lean body mass which was measured by dual-energy X-ray absorptiometry (DXA). Endothelial function was assessed by percent change in flow-mediated brachial artery dilatation (FMD). Changes in brachial artery diameter during reactive hyperemia were measured using ultrasound. Increased blood flow was induced via blood pressure cuff around the forearm, with a 5-minute inflation at 50 mmHg above the subject’s systolic blood pressure. Brachial arterial flow was determined using a pulsed-Doppler signal at baseline and 10-15 seconds after cuff release. Arterial diameter was measured at end-diastolic phase from super-VHS recordings. For reactive hyperemia response, measurements with the 5 largest diameters were averaged and the percent increase from baseline was determined as FMD. A total of 55 AA and 57 EA were included in the analysis. Mean insulin sensitivity was 4.89 in AA and 7.97 in EA (p &lt; .0001) and mean FMD was 10.69 in AA and 10.14 in EA (p = .595). Linear regression analysis indicated a significant relationship between insulin sensitivity and endothelial function in AA but not in EA (p= .005 and p= .5, respectively). These results suggest that insulin sensitivity may play a role in determining endothelial function in AA.

Oxygen Desaturation in Sleep Apnea is Inversely Associated with Vascular Changes Following Exercise Training

PURPOSE: Obstructive sleep apnea (OSA) is characterized by reductions in nocturnal mean O2 saturation (meanSpO2) that may increase cardiovascular disease morbidity. The extent to which exercise confers cardioprotection in overweight adults with different meanSpO2 profiles is not known. The purpose of this study was to examine the association of meanSpO2 with vascular function changes following exercise training in adults with and without OSA. METHODS: At baseline, participants underwent overnight polysomnography to determine the presence and severity of OSA. Tertile-based cut-off points were used to categorize meanSpO2 and apnea hypopnea index (AHI). Body fat was analyzed using dual energy X-ray absorptiometry. Vasoreactivity of the brachial artery was measured using flow-mediated dilation (FMD), while microcirculatory function was assessed via the total shear stress area under the curve (SSAUC) response during FMD. Body fat and vascular measures were repeated upon completion of a 6 week (3 sessions/wk; 1 hr/session) exercise training program. RESULTS: Thirty (age: 49+9 years; BMI: 32.0+3.8 kg/m2; 18 men: 12 women) adults with and without OSA completed the study. At baseline, adults in the highest tertile of meanSpO2 were younger than those in the lowest tertile (43+9 yrs vs. 53+7 yrs, p=0.017), yet no differences in vascular measures, AHI or total body fat percentage were observed across the tertiles. No changes in brachial artery diameter or FMD were observed across tertiles following exercise. However, the change in SSAUC in the highest tertile of meanSpO2 was greater, compared to the lowest tertile (13,636+15898 A.U. vs. -186+10879 A.U., p=0.041). Forward stepwise linear regression revealed that the highest tertile of meanSpO2 was a significant (F=5.15, p=0.036) determinant of the increased SSAUC with exercise, independent of age and baseline SSAUC. CONCLUSIONS: Severe oxygen desaturation during sleep was inversely associated with improvements in microcirculatory function following exercise training.

Effect of short‐term 17B‐estradiol on low‐flow‐mediated constriction in young women

Low‐flow mediated constriction (L‐FMC) examines vascular responses during a reduction in blood flow and provides a measure of resting shear‐stress dependent vascular tone. L‐FMC is a complementary measure to flow‐mediated dilation (FMD), and is blunted in patients with cardiovascular disease. 17β‐estradiol (E2) exerts positive effects on vascular endothelial health and can improve FMD. However, it is unknown whether E2 impacts L‐FMC.PURPOSEThe purpose of this study was to test the hypothesis that E2 administration would augment L‐FMC in young women.METHODSEleven young women (24±1 years, 24±1 kg/m2) have completed the study. To isolate the impact of E2, endogenous ovarian hormone production was suppressed with daily subcutaneous injections of a gonadotropin releasing hormone antagonist (GnRHant, 0.25 mg/day) for 10 days. E2 (0.1mg/day patch) was administered during the last 7 days of GnRHant. We measured changes in brachial artery diameter via ultrasound on day 3 of GnRHant and day 7 of E2 add‐back. A blood pressure cuff was placed just distal to the olecranon process and inflated to 200mmHg for five minutes. Images were recorded continuously at baseline (1‐minute), during occlusion (5‐minutes), and after cuff deflation (2‐minutes). L‐FMC was determined from the last 30 seconds of cuff inflation using the lowest average value and was reported as percent change from baseline diameter. FMD was calculated as a percent change from baseline to peak diameter after cuff deflation. Total vessel reactivity was calculated as the absolute value of L‐FMC and FMD. Results are reported as mean ± standard error.RESULTSBaseline diameter was similar between GnRHant (3.14 ± 0.12 mm) and E2 (3.08 ± 0.11 mm; p=0.3). L‐FMC tended to be greater during E2 administration (GnRHant −2.5 ± 0.5% vs. E2 −3.8 ± 0.5%; p=0.11). However, FMD (GnRHant 7.5 ± 0.7% vs. E2 7.6 ± 1.1%; p=0.92) and total vessel reactivity (GnRHant 10.0 ± 0.7% vs. E2 11.5 ± 1.2%; p=0.26) were not altered by E2.CONCLUSIONThese preliminary findings suggest that short term E2 administration may augment L‐FMC in young women. Additional data are needed to understand the impact of ovarian hormones on L‐FMC and its role in regulating vascular health.Support or Funding InformationNIH Grant P20 GM 103446, P20 GM 113125, U54 GM 104941, The University of Delaware Research Foundation, and AHA Award 16SDG30700015This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Comparison of Vascular Structure and Function in Obese Children and Youth

INTRODUCTION: Atherosclerotic cardiovascular disease is accelerated by early exposure to established risk factors and their persistence over time. The purpose of this pilot study was to compare vascular structure and function between obese (OB) and normal weight (NW) children and youth. METHODS: Five OB (mean ±SD; age 12.2 ± 2.0 yr) and six NW controls (13.5 ± 1.3 yr) made a single visit to DCU following an overnight fast. A blood sample was taken and left far wall (LFW) carotid intima-media thickness (cIMT), changes in brachial artery diameter (BAD) in response to shear stress and glyceryl-trinitrate, and VO2max were measured. Values are mean ±SD. RESULTS: Compared to NW participants, OB participants had a significantly higher BMI (20.85 ± 2.69 vs. 36.62 ± 3.74 kg⋅m2), waist-hip ratio (0.85 ± 0.06 vs. 0.94 ± 0.08 ), systolic blood pressure (SBP) (110.33 ± 8.33 vs 129.60 ± 2.60 mmHg) and significantly lower VO max scores (41.08 ± 13.69 vs. 24.72 ± 3.00 mL⋅kg⋅min-1⋅). LFW-cIMT was significantly higher in OB than NW (0.06 ± 0.00 vs. 0.05 ± 0.00 mm) and there was no significant group difference in BAD in response to shear stress (OB vs NW; 11.27 ± 7.94 vs. 11.79 ± 4.94 mm) or glyceryl-trinitrate (30.63 ± 10.84 vs. 29.20 ± 12.67 mm). LFW-cIMT was positively related to fasting insulin (p<0.05), BMI (p<0.001), SBP (p<0.001) and inversely related to VO2max (p<0.003). CONCLUSION: cIMT is i) higher in OB than NW children and youth, ii) positively related to SBP and BMI, and iii) inversely related to VO2max.

Cardiovascular Responses to Dynamic Handgrip Exercise in Patients with Heart Failure with Preserved Ejection Fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with symptoms of exercise intolerance, which may correspond to disease‐related changes in the peripheral circulation. A small muscle mass (dynamic handgrip, HG) exercise that evokes minimal cardiopulmonary stress was utilized to concomitantly evaluate exercising muscle blood flow and conduit vessel endothelium‐dependent vasodilation in patients with HFpEF compared to hypertensive controls (CON).MethodsWe evaluated heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and brachial artery blood velocity and diameter in CON (n = 25, 52 ± 7 y, BMI 30 ± 6 kg/m2) and patients with HFpEF (n = 25, 69 ± 10 y, BMI 33 ± 6 kg/m2) during dynamic HG exercise (15, 30, and 45% MVC, 1 contraction/sec). Brachial artery blood flow and vascular conductance were determined to quantify the hemodynamic response to HG exercise, and changes in brachial artery diameter were evaluated to assess conduit vessel vasodilatory capacity.ResultsWhile HR modestly increased in both groups at 45% MVC (10 ± 2 and 8 ± 2 bpm compared to rest, HFpEF and Control), SV and CO were unchanged across exercise intensities in both groups. Brachial artery blood flow was similar between groups at the lowest exercise intensity (15% MVC: 145 ± 41 vs. 158 ± 17 ml/min, HFpEF vs. CON) but was blunted by 20–40% in HFpEF patients at higher work rates (30% MVC: 229 ± 8 vs. 274 ± 23 ml/min, 45% MVC: 283 ± 17 vs. 399 ± 34 ml/min, HFpEF vs. CON). Brachial artery vascular conductance increased to a similar degree in both groups at 15 and 30% MVC, but was blunted by ~20% at the highest exercise intensity (45% MVC: 2.74 ± 0.21 vs. 3.54 ± 0.30 ml/min/mmHg, HFpEF vs. CON). Brachial artery shear rate was similar between HFpEF and CON at all exercise intensities. Brachial artery diameter increased across work rates in both HFpEF (15% MVC: 3 ± 1%, 30% MVC: 6 ± 1%, 45% MVC: 8 ± 1%) and CON (15% MVC: 2 ± 1%, 30% MVC: 4 ± 1%, 45% MVC: 7 ± 1%), and there was no difference between groups.ConclusionsThese results provide evidence for impaired skeletal muscle blood flow during small muscle mass exercise in patients with HFpEF that cannot be attributed to a disease‐related alteration in central hemodynamics. However, brachial artery vasodilation in response to the step‐wise, sustained shear stimulus evoked during exercise was similar between groups, suggesting a preservation of endothelium‐dependent dilation in patients with HFpEF compared to their hypertensive counterparts. Together, these findings suggest an overall derangement in the regulation of muscle blood flow during exercise in patients with HFpEF that is not attributable to disease‐related changes in endothelial function.Support or Funding InformationThis project is funded in part by the National Institutes of Health (HL118313) and the U.S. Department of Veterans Affairs (RX001697, RX001418, E6910R).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

To study the endothelial dysfunction by brachial artery flow mediated dilatation in coronary artery disease patients

Background: Brachial artery flow mediated dilatation (BAFMD), assessed by high resolution ultrasonography, reflects endothelium dependent vasodilator function. BAFMD is diminished in patients with atherosclerosis and with coronary risk factors and improves with risk reduction therapy.Methods: Study was conducted on 50 patients of coronary artery disease from In-patients who were admitted in the Department of Medicine and 25 healthy control without cardiovascular disease risk factors. All patients having established CAD i.e. Acute coronary syndrome and past history of CABG/angioplasty were included in study. Those morbidly ill and patients with evidence of chronic inflammatory or malignant disease were excluded. Doppler ultrasound of brachial artery was performed in all of them to assess baseline lumen diameter and flow mediated dilatation (i.e. percent change in brachial artery diameter after occlusion cuff release). Patients were divided into two groups; first group was classified as those having BAFMD less than 7.5% and the second group consisted patients having BAFMD less than 10%.Results: Flow mediated dilatation in cases was 6.87±5.48% as compared to the control group in which it was 13.08±3.40% and was statistically significant (P value 0.000002). Brachial artery flow mediated dilatation was abnormal in 80% cases at a cut off value &lt;10% significant abnormalities; i.e. BAFMD &lt;7.5% was found in 66% patients.Conclusions: Endothelial function as assessed by FMD is significantly impaired in patient of coronary artery disease. Hence it may be used as an important screening tool in people having cardiovascular disease risk factors and may play as a crucial role in preventive cardiology.