Postocclusive Reactive Hyperemia Research Articles

The Effect of Overweight/Obesity on Cutaneous Microvascular Reactivity as Measured by Laser-Doppler Fluxmetry: A Systematic Review

Introduction: We sought to determine by systematic review the independent effect of overweight/obesity on cutaneous microvascular reactivity in adults as measured by laser-Doppler fluxmetry. Methods: CINAHL Complete, SPORTSDiscus, Embase, Medline, and Cochrane Library were searched until March 2024 to identify studies investigating cutaneous microvascular reactivity in an overweight/obese but otherwise healthy group versus a lean/healthy weight. Reporting is consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Quality appraisal of included studies was performed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: Nineteen eligible articles reported on 1847 participants. Most articles reported impaired cutaneous microvascular reactivity in cohorts with overweight/obesity compared to cohorts with lean/healthy weight. Investigating reactivity via post-occlusive reactive hyperaemia (PORH) and iontophoresis of acetylcholine (ACh) has shown significance. No significant differences were reported between groups in response to local heating or to iontophoresis of methacholine or insulin, while findings of the effect of obesity on iontophoresis of sodium nitroprusside (SNP) were mixed. Conclusions: The pathophysiology of impaired cutaneous microvascular reactivity in overweight/obesity requires further investigation; however, impaired function of vasoactive substances, endothelial dysfunction, sensory nerves, and calcium-activated potassium channels may be implicated. Identifying these impaired microvascular responses should inform possible therapy targets in overweight and obesity.activated potassium channels may be implicated. Identifying these impaired microvascular responses should inform possible therapy targets in overweight and obesity.

Impaired systemic microvascular function in patients with resistant arterial hypertension and microalbuminuria: an observational study

Abstract Background Systemic arterial hypertension (SAH) is one of the most prevalent diseases worldwide and is known to be associated with alterations of microvascular function. It is well known that microalbuminuria (MAU) is considered an early marker of renal and cardiac injury in SAH and is an independent risk factor for cardiovascular events in this population. Additionally, it is associated with altered endothelial function, which occurs from the early stages and can be considered an early marker. In some cases, SAH presents as resistant arterial hypertension (RAH), resulting in a worse prognosis compared to individuals with non-resistant hypertension. Moreover, MAU is associated with higher mortality, independent of glomerular filtration rate. Endothelial dysfunction is also a risk marker found in different conditions and can add to MAU in patients with RAH. Purpose To investigate systemic microvascular function in patients with RAH, with or without MAU. Methods 64 patients with RAH, of both genders (50% men), were evaluated, with 32 having MAU and 32 without MAU (defined as a urinary albumin/creatinine ratio between 30 and 300 mg/g in a routine urine sample). Microvascular function assessment was performed using a laser speckle system, allowing analysis of cutaneous microvascular flow. Flow measurements were expressed in arbitrary perfusion units (APU) divided by the mean arterial pressure to obtain cutaneous vascular conductance (CVC). A post-occlusive reactive hyperemia (PORH) test was performed, with brachial artery occlusion using a sphygmomanometer 50 mmHg above systolic pressure for 3 minutes; cutaneous flow was measured after release of the occlusion. Results Patients with or without MAU did not differ in terms of age, frequency of diabetes, and chronic kidney disease. The peak CVC values during PORH were 0.64 ± 0.15 and 0.55 ± 0.15 APU/mmHg in RH and RH + MAU patients, respectively (P=0.03). The delta values (peak – baseline) during PORH were 0.31 ± 0.11 and 0.25 ± 0.09 APU/mmHg in RH and RH + MAU patients, respectively (P=0.04)(Figure 1). Conclusions PORH-induced vasodilation was found to be reduced in patients with RAH and MAU compared to patients without MAU. This finding shows alteration of endothelium-dependent vasodilation mechanisms in these patients, indicating reduced systemic microvascular endothelial function. Endothelial dysfunction may be associated with glomerular permeability changes, contributing to MAU and further increasing the risk for these patients. This suggests the need for more intensive therapeutic interventions and better risk stratification for these patients, as endothelial dysfunction can be found in the early stages of the disease.Figure 1

Increased fatigability and impaired skeletal muscle microvascular reactivity in adults with obstructive sleep apnea: a cross-sectional study

BackgroundSympathetic nervous system hyperactivity and chronic intermittent nocturnal hypoxia in individuals with obstructive sleep apnea (OSA) predispose them to microvascular impairment, which may contribute to increased daytime muscle fatigue. This study aimed to assess microvascular reactivity of the skeletal muscle, examine fatigability, and determine the relationship between fatigability and microvascular reactivity in adults with OSA.MethodsTwenty-six participants were allocated into two groups—those with OSA and those without i.e. non-OSA. Each group comprised of 13 individuals who underwent an arterial occlusion test on their non-dominant leg. The percentage change of maximal hyperemic response (MHR) and the time to achieve MHR (tM) of both the total myoglobin/hemoglobin (∆[Hbtot]) and the oxygenated myoglobin/hemoglobin (∆[HbO2]) signals from near-infrared spectroscopy were calculated to examine microvascular reactivity. In addition, a 10-min walk test was performed to assess performance and perceived fatigability.ResultsThe OSA group demonstrated a reduced in ∆[Hbtot]MHR (150.9 ± 16.2% vs. 235.8 ± 72.7%, p = 0.006), ∆[HbO2]MHR (131.4 ± 8% vs. 161.7 ± 10.6%, p = 0.001) and increased ∆[Hbtot]tM (80.5 ± 13.1 s vs. 47.7 ± 9.9 s, p < 0.001), ∆[HbO2]tM (85.2 ± 22.4 s vs. 52.1 ± 5.9 s, p = 0.001) compared to the non-OSA group. In addition, participants in the OSA group experienced greater perceived (6 ± 1 vs. 2.8 ± 0.1, p = 0.001) and performance fatigability (1.1 ± 0.1 vs. 0.9 ± 0.1, p = 0.001) compared to adults in the non-OSA group. Moreover, both performance and perceived fatigability were significantly associated with microvascular reactivity parameters (all p < 0.05).ConclusionMicrovascular dysfunction, as determined by an attenuated post-occlusive reactive hyperemia, is observed in individuals with OSA that may contribute to increased fatigability in these individuals.

Acute impact of inorganic nitrate supplementation after ischemia and during small muscle mass exercise in postmenopausal females: A pilot study.

Menopause is associated with reduced endothelial-dependent vasodilation and increased cardiovascular disease (CVD) risk. Dietary nitrate, a non-pharmacological approach, may increase vasodilatory capacity consequentially reducing CVD risk. We investigated macro- and microvascular function after acute nitrate supplementation in postmenopausal females (PMF). Vascular function was studied with flow-mediated vasodilation (FMD) and near-infrared post occlusive reactive hyperemia (PORH). Incremental handgrip exercise was performed to investigate blood flow and tissue oxygenation. We hypothesized acute dietary nitrate would not impact resting endothelial measures but would increase post ischemic vasodilation and incremental exercise blood flow. Late-phase PMF (n = 12) participated in a randomized crossover design with 140 mL of nitrate-rich (NR) beetroot juice or nitrate-poor black currant juice. Testing included a 5-min FMD, a 3-min ischemic exercise FMD, and incremental exercise at 10%, 15%, and 20% maximal voluntary contraction to measure blood flow and pressure responses. A p ≤ 0.05 was considered significant. One-way ANOVA indicated lower resting pressures, but no change to FMD, or PORH in either protocol. Two-way repeated measures ANOVA indicated NR supplementation significantly reduced mean arterial pressure at rest and during incremental exercise at all intensities without changes to blood flow. Acute nitrate is effective for resting and exercising blood pressure management in PMF.

Multiscale optoacoustic assessment of skin microvascular reactivity in carotid artery disease

Microvascular endothelial dysfunction may provide insights into systemic diseases, such as carotid artery disease. Raster-scan optoacoustic mesoscopy (RSOM) can produce images of skin microvasculature during endothelial dysfunction challenges via numerous microvascular features. Herein, RSOM was employed to image the microvasculature of 26 subjects (13 patients with single carotid artery disease, 13 healthy participants) to assess the dynamics of 18 microvascular features at three scales of detail, i.e., the micro- (<100μm), meso- (≈100-1000μm) and macroscale (>1000μm), during post-occlusive reactive hyperemia challenges. The proposed analysis identified a subgroup of 9 features as the most relevant to carotid artery disease because they achieved the most efficient classification (AUC of 0.93) between the two groups in the first minute of hyperemia (sensitivity/specificity: 0.92/0.85). This approach provides a non-invasive solution to microvasculature quantification in carotid artery disease, a main form of cardiovascular disease, and further highlights the possible link between systemic disease and microvascular dysfunction.

Microvascular effects of a mixed meal tolerance test: a model validation study

AbstractPurposeEndothelial dysfunction is a pathophysiological change preceding many cardiovascular events. Measuring improvements of endothelial function is challenging when function is already optimal, which may be remediated using a physiological challenge. This study aimed to determine whether imaging assessments can detect microvascular effects of a mixed meal tolerance test (MMTT).MethodsTwenty healthy volunteers (age ≥45 and ≤70 years) underwent two MMTTs at the beginning (Day 1) and end (Day 84) of a twelve‐week period. Imaging methods included laser speckle contrast imaging (LSCI) combined with post‐occlusive reactive hyperaemia (PORH) and local thermal hyperaemia (LTH) challenges, passive leg movement ultrasonography (PLM), and sidestream dark field microscopy (SDFM). Measurements were conducted pre‐MMTT and at 5 timepoints post‐MMTT for PLM and SDFM and 3 timepoints post‐MMTT for PORH and LTH.ResultsNo consistent effects of the MMTT were detected on LSCI LTH, PLM and SDFM endpoints. LSCI PORH maximum perfusion was significantly suppressed 46, 136, and 300 min post‐MMTT administration on Day 1, while residual perfusion decreased significantly 46 and 136 min post‐MMTT on Day 1. However, when repeated on Day 84, PORH endpoints were not significantly affected by the MMTT.ConclusionSDFM, PLM and LSCI LTH endpoints displayed high intra‐subject variability and did not detect consistent effects of MMTT. LSCI PORH endpoints displayed the lowest intra‐subject variability of all assessed endpoints and were affected by the MMTT on Day 1, but not on Day 84. Further standardization of methods or more robust challenges to affect vascular endpoints may be needed.

Reduced systemic microvascular function in patients with resistant hypertension and microalbuminuria: an observational study.

Resistant hypertension (RH) may be associated with microalbuminuria (MAU), a marker of cardiovascular risk and target organ damage, and both may be related to microvascular damage. Laser speckle contrast imaging (LSCI) is an innovative approach for noninvasively evaluating systemic microvascular endothelial function useful in the context of RH with or without MAU. Microalbuminuria was defined as a urine albumin-to-creatinine ratio between 30 and 300 mg/g. Microvascular reactivity was evaluated using LSCI to perform noninvasive measurements of cutaneous microvascular perfusion changes. Pharmacological (acetylcholine [ACh], or sodium nitroprusside [SNP]) and physiological (postocclusive reactive hyperemia [PORH]) stimuli were used to evaluate vasodilatory responses. Thirty-two patients with RH and a normal urine albumin-to-creatinine ratio (RH group) and 32 patients with RH and microalbuminuria (RH + MAU) were evaluated. Compared with patients without MAU, patients with RH + MAU showed reduced endothelial-dependent systemic microvascular reactivity, as demonstrated by an attenuation of microvascular vasodilation induced by PORH. On the other hand, ACh-induced vasodilation did not differ between groups. The results also revealed reduced endothelial-independent (SNP-induced) microvascular reactivity in hypertensive patients with MAU compared with patients without MAU. In this study, there was evidence of endothelial dysfunction associated with impaired microvascular smooth muscle function in patients with RH + MAU. This may suggest that patients with RH need more intensive therapeutic strategies for the control of blood pressure to avoid further vascular damage and the resulting consequences.The study was registered at ClinicalTrials.gov ( https://register.clinicaltrials.gov ) under protocol # NCT05464849, initial release 12/07/2022.

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

DETECTION AND QUANTIFICATION OF MICROCIRCULATORY DYSFUNCTION IN SEVERE COVID-19 NOT REQUIRING MECHANICAL VENTILATION: A THREE-ARM COHORT STUDY.

Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non-COVID-19 intensive care unit (ICU)-matched controls. A validation cohort included healthy, comorbidity-free patients. The primary outcome compared tissue oxygen resaturation slope (rStO 2 ) in COVID-19 patients and non-COVID ICU controls. rStO 2 was measured post a 3-min vaso-occlusive test during post-occlusive reactive hyperemia (PORH). Additionally, microvascular reactivity was assessed using perfusion index (PI) during PORH and laser speckle contrast imaging post iontophoresis with acetylcholine (ACH), sodium nitroprusside (SNP), and sublingual microcirculation. Results: Overall, 75 patients (25 per cohort) were included. COVID-19 patients exhibited greater severity than ICU controls, as indicated by their SOFA scores (4.0 [3.0; 4.0] vs. 1.0 [0; 1.0], P < 0.001) and PaO 2 /FiO 2 ratios (113 [82; 150] vs. 443 [348; 533], P < 0.001). No significant difference was observed in rStO 2 between the groups. COVID-19 patients showed longer time in reaching peak PI ( P = 0.025), reduced vasodilation with ACH and SNP ( P = 0.010 and P = 0.018, respectively), and increased microvascular density ( P = 0.019) compared to non-COVID-19 ICU controls. Conclusion: We observed evidence of MD in COVID-19 patients through various microcirculatory parameters. This study's reproducible multimodal approach facilitates acute MD detection across multiple clinical applications. Limitations included the observational design, limited statistical power, single-time microvascular measurements, varying illness severity among groups, and possible influences of treatments and vaccinations on MD. Trial registration : Clinical-Trials.gov (NCT04773899).

Impaired Microvascular Reactivity in Patients with Chronic Kidney Disease Submitted to Kidney Transplantation: A Prospective Observational Study.

The effect of kidney transplantation on endothelial dysfunction and autonomic dysfunction in uremia remains controversial, and few studies have evaluated this question. Endothelial dysfunction and autonomic dysfunction, both, be assessed noninvasively using laser Doppler flowmetry (LDF). This study evaluated cutaneous microvascular blood flow and reactivity using LDF in patients undergoing kidney transplantation. This prospective longitudinal cohort study involved 40 patients with chronic kidney disease (CKD) undergoing kidney transplantation, compared with 40 patients without kidney disease. Using LDF, post-occlusive reactive hyperemia (PORH) (resting flow [RF], peak flow, ratio between peak, and RF, hyperemic area, PORH index), and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values) were evaluated. RF and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values), were lower in the CKD group at 1 week and at 3 months after transplantation (p &lt; 0.005). Mean minimum inspiratory values increase in the CKD group, 3 months after transplantation. Compared with controls with no CKD, in CKD patients undergoing kidney transplantation, microcirculation by LDF shows improvement after 3 months.

Robust analysis of microcirculatory flowmotion during post-occlusive reactive hyperemia

BackgroundFlowmotion analysis of the microcirculatory blood flow is a method to extract information about the vessel regulatory function. It has previously shown promise when applied to measurements during a post-occlusive reactive hyperemia. However, the reperfusion peak and the following monotonic decline introduces false low frequencies that should not be interpreted as rhythmic vasomotion effect. AimTo develop and validate a robust method for flowmotion analysis of post-occlusive reactive hyperemia signals. MethodThe occlusion-induced reperfusion response contains a typical rapid increase followed by a monotonic decline to baseline. A mathematical model is proposed to detrend this transient part of the signal to enable further flowmotion analysis. The model is validated in 96 measurements on healthy volunteers. ResultsApplying the proposed model corrects the flowmotion signal without adding any substantial new false flowmotion components. ConclusionFuture studies should use the proposed method or equivalent when analyzing flowmotion during post-occlusive reactive hyperemia to ensure valid results.

Juvenile primary hypertension is associated with attenuated macro- and microvascular dilator function independently of body weight.

Hypertension has become a global medical and public health issue even in childhood. It is well accepted that hypertension is associated with impaired endothelium-dependent vascular reactivity in adult patients. However, there is a lack of data on hypertension-related endothelial dysfunction in hypertensive children. Thus, present study aimed to evaluate the association of primary hypertension in the pediatric population with macro- and microvascular function, and to assess the potential role of oxidative stress in that connection. Fifty-two children were enrolled in this study; 26 normotensive (NT) and 26 with primary hypertension (HT), both sexes, 9-17 years old. In addition to anthropometric, hemodynamic and biochemical measurements, peripheral microvascular responses to occlusion (postocclusive reactive hyperemia, PORH), local heating (local thermal hyperemia, LTH), iontophoretically applied acetylcholine (AChID) and sodium nitroprusside (SNPID) were evaluated by laser Doppler flowmetry (LDF). Furthermore, brachial artery flow-mediated dilation (FMD) was measured and biomarker of oxidative stress was determined. PORH, AChID and LTH were impaired in hypertensive compared to normotensive children, while SNPID did not differ between groups. FMD was decreased in hypertensive compared to normotensive children. Serum concentration of 8- iso -PGF2α was significantly elevated in hypertensive compared to normotensive children. Even in childhood, primary hypertension is associated with attenuated endothelial function and reduced endothelium-dependent responses to various physiological stimuli. Juvenile hypertension is related to increased level of vascular oxidative stress. All changes are independent of BMI.

Effect of Encapsulated Purple Garlic Oil on Microvascular Function and the Components of Metabolic Syndrome: A Randomized Placebo-Controlled Study-The ENDOTALLIUM Study.

Endothelial dysfunction (ED) is associated with progressive changes contributing to clinical complications related to macro- and microvascular diseases. Garlic (Allium sativum L.) and its organosulfur components have been related to beneficial cardiovascular effects and could improve endothelial function. The ENDOTALLIUM Study aimed to evaluate the effect of the regular consumption of encapsulated purple garlic oil on microvascular function, endothelial-related biomarkers, and the components of metabolic syndrome (MetS) in untreated subjects with cardiometabolic alterations. Fifty-two individuals with at least one MetS component were randomized (1:1) in a single-center, single-blind, placebo-controlled, parallel-group study. The participants received encapsulated purple garlic oil (n = 27) or placebo (n = 25) for five weeks. Skin microvascular peak flow during post-occlusive reactive hyperemia significantly increased in the purple garlic oil group compared to the placebo group (between-group difference [95%CI]: 15.4 [1.5 to 29.4] PU; p = 0.031). Likewise, hs-CRP levels decreased in the purple garlic group compared to the control group (-1.3 [-2.5 to -0.0] mg/L; p = 0.049). Furthermore, we observed a significant reduction in the mean number of MetS components in the purple garlic group after five weeks (1.7 ± 0.9 vs. 1.3 ± 1.1, p = 0.021). In summary, regular consumption of encapsulated purple garlic oil significantly improved microvascular function, subclinical inflammatory status, and the overall MetS profile in a population with cardiometabolic alterations.

An evaluation of the effects of localised skin cooling on microvascular, inflammatory, structural, and perceptual responses to sustained mechanical loading of the sacrum: A study protocol.

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.

The Impact of Disease Duration on Microcirculatory Dysfunction in Young Patients with Uncomplicated Type 1 Diabetes.

This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO2_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO2_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests.

Possibilities of noninvasive diagnostics of cardiovascular diseases associated with atherosclerosis

Background. Despite the global trend towards a decrease in mortality from cardiovascular pathology of atherosclerotic genesis, this group of diseases continues to occupy a leading position in the structure of disability and mortality among the population of many countries. Aim. Identification of noninvasive markers of arterial wall lesions associated with the presence of arterial hypertension (AH) and coronary heart disease (CHD) in persons younger than 55 years. Materials and methods. The study included 81 people. Three groups were distinguished from them: 1st (n=31) – a control group of practically healthy individuals, average age – 43 (40; 48) years; 2nd group (n=21) – patients with coronary heart disease without a history of cardiovascular diseases (CVD), average age – 45,5±6,1; group 3 (n=29) – patients with AH without CHD, average age – 47 (35; 50) years. The parameters of a biochemical blood test were determined, volumetric sphygmography and a sample with post-occlusive reactive hyperemia were performed. Results. In groups of patients with CHD and AH, negative changes in the lipid profile and higher glucose levels were recorded compared to healthy individuals. According to the results of volumetric sphygmography, the pulse wave velocity in arteries of predominantly elastic type (R/L-PWV) in group 1 was 10.1±1.7 m/s, in group 2 – 12.9±1.8 m/s, in group 3 – 13.1 (12; 14) m/s (р1–2=0.029; р1–30.001); cardio-ankle vascular index (CAVI) – 6.5±0.7, 7.7 (7; 8.7) and 7.8 (7.3; 8.4), respectively (р1–20.001; р1–30.001). According to the data of the test with post-occlusive reactive hyperemia, a comparably high frequency of pathological values of flow-dependent vasodilation (FDV) and reactivity index (RI) was demonstrated in patients with CHD and AH (р1–20.05; р1–30.05). A multifactorial model of noninvasive diagnosis of CHD in individuals without a history of CVD, including non-high-density lipoprotein cholesterol, R/L-PWV, and FDV, has been developed. For patients with AH, glucose, lipid metabolism, R/L-PWV, pulse wave velocity in muscle-type arteries (B-PWV), augmentation index (AI), biological age, CAVI, FDV, RI were the risk factors for the presence of the disease in the anamnesis. Conclusion. The results obtained confirm the importance of an integrated approach in the screening diagnosis of CVD.

Endothelial function cannot be assessed by the reactive hyperemia following occlusion

Reactive hyperemia (RH) and the post occlusive reactive hyperemia (PORH) are known to assess vascular function in vivo and referred as useful prognostic tools in vascular medicine. However, its translation to clinical practice is poor due to important unsolved inconsistencies. Our group has been studying the adaptive responses following RH. Here we clarify the involved mechanism, its impact on general hemodynamics and the significance of these responses. A convenience sample of fourteen healthy women (48.0 ± 8.0 y.o.) was selected, all being normotensive non-menopausal, with no signs of vascular impairment (normal ankle-brachial index and mean arterial pressure MAP), and with (self-reported) equivalent levels of physical activity. The study followed all principles of good clinical practice established for human research and was previously approved by the institutional Ethics Committee. The protocol included three phases—a baseline register (Phase I) during rest, giving place to the occlusion as part of the PORH maneuver challenge period (Phase II) with one minute, followed by a ten-minute recovery period (Phase III). PORH was performed on one randomly chosen upper limb, using the cuff of the TASK FORCE® platform for the continuous monitoring of blood pressure and hemodynamics. After baseline acquisition, the cuff was rapidly inflated with 200 mmHg to occlude the brachial artery for one minute. Then the cuff was rapidly deflated, and signals registered for recovery recordings. Perfusion was measured in both hands by laser Doppler flowmetry (3rd finger) with a Perimed5000 system. To confirm previous evidence regarding the mechanism(s) involved, we also accessed the RH impact(s) on the contralateral forearm skin circulation by functional imaging using a multi-scan photoptoacoustic tomography (PAT) (MSOT iThera system). The tissue hypoxia related to RH-PORH is referred to evoke a local vasodilation, such that hyperemia occurs following the cessation of occlusion. Thus, any reduction of this response has been associated to endothelial impairment. However, our studies have shown suffcient evidence of a centrally mediated reflex rather than a local response mediated by local vasodilators. In fact, LDF clearly detected significant perfusion reductions in both hands during and following occlusion, more pronounced in the challenged limb, while PAT confirmed similar changes in the superficial plexus on the contralateral forearm. Additionally of interest, no significant hemodynamical changes were found with PORH apart from MAP when comparing recovery with baseline periods. Our results clearly show that the physiological significance of RH or POHR reduction can no longer be regarded to solely represent “endothelial disfunction” but rather an expression of a global adaptive hemodynamical response, centrally mediated, that might originate essential endpoints also measurable in the contralateral limb, with clinical utility. This research was financed by national funds through FCT - Foundation for Science and Technology, I.P. (Portugal), under the [UIDB/04567/2020] and [UIDP/ 04567/2020] projects, and by COFAC/ALIES for the use of the photoacoustic instrument. This is the full abstract presented at the American Physiology Summit 2024 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.

Peripheral Endothelial and Microvascular Function with Repeated Far-infrared Sauna in Adults with Obesity

Obesity can lead to vascular dysfunction and elevated cardiovascular risk. Repeated far-infrared sauna bathing has improved cardiovascular function in cardiac patients. It is unknown if repeated far-infrared sauna bathing improves vascular function in adults with obesity. Purpose: We hypothesized that brachial artery flow-mediated dilation (FMD) and post-occlusion reactive hyperemia would be improved after 30 far-infrared sauna sessions in adults with obesity. Methods: Five adults with obesity (4 men, 1 woman; age: 33 ± 11; BMI: 36.3 ± 4.2 kg/m2) were assigned to a heat therapy (n=3) or time-control group (n=2). The heat therapy group completed 30 sessions of far-infrared sauna bathing (43 ± 4 min at 54 ± 2°C) at 3-4 times/week for 9 weeks. Peripheral vascular function was assessed before (PRE) and after (POST) the intervention. Brachial artery diameter and blood velocity were recorded via Doppler ultrasound for 1 min of baseline, 5 min of forearm occlusion, and 3 min of post-occlusion. FMD was calculated as the percent change from baseline diameter to peak diameter during post-occlusion. Relevant shear rate was calculated as the area under the curve (AUC) to peak dilation. Peak post-occlusion reactive hyperemia was defined as the peak blood flow during post-occlusion. Total post-occlusion reactive hyperemia was calculated as the AUC for blood flow above baseline for 3 min. Results: Baseline diameter did not differ at PRE vs. POST or between Control (3.76 ± 0.08 vs. 3.78 ± 0.09 mm) and Heat (4.25 ± 0.03 vs. 4.25 ± 0.02 mm) (all p &gt; 0.3977). FMD did not differ at PRE vs. POST and between Control (11.2 ± 5.2 vs. 10.6 ± 10.2%) or Heat (2.8 ± 2.4 vs. 6.2 ± 4.2%) (all p &gt; 0.2684). Relevant shear rate AUC did not differ at PRE vs. POST or between Control (27,412 ± 7,506 vs. 31,251 ± 20,608 a.u.) and Heat (16,538 ± 11,617 vs. 24,952 ± 10,639 a.u.) (all p &gt; 0.2577). Peak post-occlusion reactive hyperemia did not differ at PRE vs. POST or between Control (396 ± 42 vs. 387 ± 17 ml/min) and Heat (464 ± 40 vs. 441 ± 32 ml/min) (all p &gt; 0.1049). Total post-occlusion reactive hyperemia AUC was lower in Heat (140 ± 7 ml) vs Control (262 ± 12 ml) at PRE but did not differ across time or between groups at POST for Heat (212 ± 35 ml) vs Control (246 ± 66 ml). Conclusions: These preliminary data suggest there is no effect of 30 sessions of far-infrared sauna bathing on peripheral endothelial and microvascular function in adults with obesity. This may be due to the duration, frequency, and intensity of the far-infrared sauna compared to other passive heating modalities that have generated beneficial vascular adaptations in other studies. AHA 19TPA34890033. This is the full abstract presented at the American Physiology Summit 2024 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.

Central and peripheral cardiovascular responses after acute dietary nitrate supplementation in post-menopausal women

The transition to menopause is accompanied by augmented cardiovascular disease risk, partially attributed to reduced nitric oxide (NO) bioavailability. Despite a lower arterial stiffness than men, postmenopausal women are susceptible to increased aortic pulsatile hemodynamic load because of greater pressure wave reflection and vascular dysfunction. Increasing bioavailable NO with dietary nitrate has shown promise to reduce aortic (aSBP) and brachial (bSBP) systolic pressure healthy postmenopausal women. However, there are limited reports comparing hypertensive (HTN) and normotensive (NTN) postmenopausal women regarding wave separation analysis and vascular function following dietary nitrate supplementation. This study investigated if acute dietary nitrate supplementation would improve aortic hemodynamics, wave reflection characteristics, vascular stiffness, and vasodilatory function. We hypothesized that dietary nitrate would lower pulse wave velocity in hypertensives, lower aortic and brachial blood pressures and forward and backward wave magnitude and increase microvascular, but not macrovascular function in both groups. Fourteen postmenopausal women (n=7 HTN; n=7 NTN) participated in a two-day randomized crossover study design with dietary nitrate (nitrate rich, NR) or a placebo control (NP). Central and peripheral hemodynamics and carotid-femoral pulse wave velocity (cfPWV) were performed with a SphygmoCOR Excel, simultaneous resting macro- and- microvascular function was assessed using flow-mediated vasodilation (FMD) and post occlusive reactive hyperemia (PORH) using near-infrared spectroscopy. aSBP was reduced significantly following NR supplement within groups (HTN: NP 126±2 NR 120±1mmHg) and NTN group (NP 110± 1 NR 104±3mmHg p&lt;0.05). Forward pulse height HTN (NP 29±1.4 NR 26.3±1.4mmHg) NTN (NP 25.6±0.9 NR 24±2.7mmHg) and reflected pulse height HTN (NP 18.2±0.08 NR 17.2±0.4mmHg) NTN (NP 17.7±0.2 NR 15.7±1.07mmHg) were not different. cfPWV was faster in the HTN group and slowed with a NR supplement (HTN: NP 8.2±0.29 NR 7.4±0.31m/s; NTN NP 7.1±0.23 NR 6.6±0.62m/s p&lt;0.05). A significant interaction for %FMD was found (HTN: NP 7.3±0.8 NR 6.2±0.8%; NTN NP 6.6±0.7 NR 9.4±0.7%). Further, we found no difference in the NIRS derived microvascular function measurements (HTN: NP 1.9±0.2 NR 1.7±0.3%/s; NTN NP 1.6±0.1 NR 1.4±0.2%/s p&gt;0.05). These data indicate that dietary nitrate consumption led to a substantial reduction in aortic hemodynamics and reduced pulse wave velocity regardless of hypertension status. Interestingly, macrovascular, but not microvascular vasodilatory function was improved in the NTN women only. Dietary nitrate supplementation appears to have differential effects when considering HTN and NTN postmenopausal women. Supported with funds from The University of Wisconsin-La Crosse RSEL graduate grant. This is the full abstract presented at the American Physiology Summit 2024 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.

Racial Disparity in Microvascular Function in Men with Newly Diagnosed Prostate Cancer

BACKGROUND:Cardiovascular disease (CVD) is a leading cause of death in men with prostate cancer. In addition, non-Hispanic Black (NHB) men experience worse CVD-related mortality compared to their non-Hispanic White (NHW) counterparts, although the reason for this racial disparity remains unclear. Notably, vascular endothelial dysfunction often precedes the emergence of overt CVD. Indeed, conduit-vessel dysfunction, micro-vascular dysfunction, and arterial stiffness are independent predictors of CVD risk. Thus, the purpose of this study was to comprehensively assess vascular health in recently diagnosed NHB and NHW men with prostate cancer. Methods: Twenty-eight men (10 NHW, 18 NHB) with a new clinical diagnosis of prostate cancer (within 3 months) participated in this study. Flow-mediated dilation (FMD) was performed to represent conduit-vessel vascular endothelial function. Cutaneous post occlusive reactive hyperemia (PORH) with local thermal heating (LTH) and iontophoresis of acetylcholine were performed to represent various mechanisms regulating microvascular function. Lastly, pulse wave velocity (PWV) and pulse wave analysis (PWA) were performed to assess central and aortic stiffness, respectively. Data are reported as mean ± SD. Results: A 4-year age difference ( p=0.131) was observed between NHB (65±7 years) and NHW (69±6 years) men. No differences in BMI or clinical laboratory values were observed between NHB and NHW patients (all p&gt;0.05). NHB men exhibited significantly lower microvascular function compared to NHW men, including PORH (NHB: 117±44 PU vs NHW: 207±47 PU; p&lt;0.001), LTH (NHB: 180±73 PU vs NHW: 281±65 PU; p=0.003), and iontophoresis (NHB: 67±28 PU vs NHW: 136±38 PU; p&lt;0.001). No differences in FMD ( p=0.596), PWV ( p=0.695), or PWA ( p=0.883) were observed between groups. CONCLUSION: The results of the current study provide compelling evidence that microvascular dysfunction is present in NHB men who are recently diagnosed with prostate cancer compared to their NHW counterparts. Given that NHB men were 4 years younger, these data support that the microvascular dysfunction may accelerate vascular aging and contribute to the racial disparity in CVD following prostate cancer diagnosis. Supported by: AHA SFRN 863621 (RAH). This is the full abstract presented at the American Physiology Summit 2024 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.