Postocclusive Hyperemia Research Articles

Effects of occlusion pressure on hemodynamic responses recorded by near-infrared spectroscopy across two visits.

Ischemic Preconditioning (IPC) has emerged as a promising approach to mitigate the impact of hypoxia on physiological functions. However, the heterogeneity of occlusion pressures for inducing arterial occlusion has led to inconsistent hemodynamic outcomes across studies. This study aims to evaluate the peripheral hemodynamic responses to partial and total blood-flow occlusions on the left arm at rest, using absolute or individualized pressures, on two occasions. Thirty-five young males volunteered to participate in this study. IPC procedure (3 × 7-min) was performed on the left upper arm with cuff pressures at 50mmHg (G1), 50mmHg over the systolic blood pressure (SBP + 50mmHg) (G2) or 250mmHg (G3). NIRS-derived parameters were assessed for each occlusion and reperfusion phase in the brachioradialis. Results showed a significantly lower magnitude of deoxygenation (TSIAUC) for G1 compared to G2 (-1959.2 ± 1417.4 vs. -10908.1 ± 1607.5, P < 0.001) and G3 -1959.2 ± 1417.4 vs. -11079.3 ± 1828.1, P < 0.001), without differences between G2 and G3. However, G3 showed a significantly faster reoxygenation only for tissue saturation index (TSIslope) compared to G2 (1.3 ± 0.1 vs. 1.0 ± 0.2, P = 0.010), but without differences in the speed of recovery of deoxyhemoglobin [(HHb) slope], or in the magnitude of post-occlusive hyperemia (PORH). Besides TSI reoxygenation speed, G2 and G3 elicit comparable resting hemodynamic responses measured by NIRS. Thus, this study highlights the practicality and effectiveness of using relative occlusion pressures based on systolic blood pressure (SBP) rather than relying on excessively high absolute pressures.

Маркери психоемоційного стресу у жінок київського регіону в період російсько-української війни

War-related stress (WSR) leads to disruption of vital physiological functions, which can accelerate the development of age-related pathology and early mortality. Therefore, the study of the impact of SPV on the functioning of various body systems requires an in-depth analysis. The purpose of the study is to assess the level of psycho-emotional stress, anxiety, and depression and to investigate their influence on indicators of endothelial function, lipid, carbohydrate metabolism, autonomic nervous regulation of the cardiovascular system) in women of the Kyiv region during the Russian-Ukrainian war. 56 women aged 30-78 were examined (average age - 53.45 ± 1.6 years), who had been in the Kyiv region without permission since the beginning of the Russian-Ukrainian war (February 24, 2022). The control group consisted of 79 women aged 29-85 years, (average age - 56.46 ± 1.44 years), who were examined before the start of the Russian-Ukrainian war in 2018-2021. Anthropometric parameters, fasting plasma glucose level and standard oral glucose tolerance test (OGTT), serum lipid concentration, plasma cortisol level were determined. The function of the endothelium of microvessels was studied by the method of laser Doppler flowmetry in a sample with reactive post-occlusion hyperemia, the state of autonomic regulation of the cardiovascular system by the method of heart rhythm variability analysis. Psychoemotional state using the PLC-5 scale, Beck depression scale, Spielberger-Hanin test, the state of cognitive function was studied using the Montreal Cognitive Assessment (MoCA) A statistically significant increase in the level of cortisol, as an important marker of WSR, was revealed, compared to the control group. Excessive psycho-emotional stress of the body during the war is also evidenced by the predominance of the sympathetic link of autonomous nervous regulation in women. The development of endothelial dysfunction and the negative impact of WSR on lipid and carbohydrate metabolism were confirmed, which was combined with a decrease in mental performance indicators, an increase in the levels of personal and situational anxiety, and depression. An increase in the level of cortisol and the activity of the sympathetic link of the autonomic nervous system indicates the presence of chronic psychoemotional stress, which increases the levels of anxiety and depression, reduces the mental performance of women in war conditions and leads to the development of endothelial dysfunction, disorders of lipid and carbohydrate metabolism.

Evaluation of inter-rater and test-retest reliability for near-infrared spectroscopy reactive hyperemia measures.

Near-infrared spectroscopy (NIRS) is a non-invasive tool used to measure blood flow in peripheral tissues. More information on inter-rater agreement and test-retest reliability of NIRS-based reperfusion assessments is needed. To assess inter-rater agreement for NIRS based data analysis, and evaluate the measurement's reliability across days. On three separate days (average days between visits 1 and 3: 19.4±6.9days), participants' (N=15 males, 22±2yr.) post-occlusion reactive hyperemia (PORH) was measured in the left gastrocnemius muscle using Continuous-Wave NIRS (CW-NIRS). A blood pressure cuff was placed proximal to the knee and inflated to occlude lower leg blood flow for 5min. The following CW-NIRS parameters were selected: (1) percent saturation in HbO2 (StO2%) at baseline; (2) the O2Hb range used to normalize the NIRS signal; (3) the time for the O2Hb signal to reach 50% peak post-occlusion hyperemia (T1/2), and (4) the post peak hyperemic O2Hb recovery slope (O2REC-SLP). Absolute agreement between the two analysts was calculated using two-way random effects Intraclass Correlation Coefficients (ICC2,1). Consistency between analysts and across days was calculated using two-way mixed models (ICC3,1). Mean and 95% confidence intervals (CI) of ICCs are reported. Coefficient of variation (CV) and standard error of the measurement (SEM) are reported. The ICC2,1 data indicated "adequate" to "excellent" absolute agreement between the two NIRS analysts. ICC2,3 data indicated "adequate" to "good" reliability across visits. The CV and SEM for rater 1 and rater 2 across visit were StO2 (CV: 3.79%±2.71% and 4.50%±2.37%; SEM: 3.42 and 3.82), O2Hb range (CV: 10.50±5.93 and 12.79±12.41; SEM: 3.26 and 4.71), T1/2 (CV: 11.15%±5.52% and 10.96%±4.50; SEM: 1.22 and 1.11), and O2REC-SLP (CV: 19.49%±9.99% and 18.45%±9.48%; SEM: 0.04 and 0.04). It is concluded that NIRS parameters assessed show adequate reliability between analysts and across three visits. It is recommended, when feasible and because of the absence of 100% reliability, that investigators employ more than one rater for scoring at least a portion of the data across each trial in a study's control condition in order to have the ability to estimate the magnitude of error attributable to imperfect reliability.

Arterial occlusion duration affects the cuff-induced hyperemic response in skeletal muscle BOLD perfusion imaging as shown in young healthy subjects

ObjectiveDynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal muscle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration.Materials and methodsBOLD images were acquired at 3 T in 14 healthy volunteers. {mathrm{T}}_{2}^{*}-imaging with 5- and 1.5-min occlusions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based {mathrm{T}}_{2}^{*}-time curves. Differences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra- and inter-scan repeatability were evaluated with coefficient of variation.ResultsLonger occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant.DiscussionFindings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments.

Positive effects of Quercetin, Iron Oxide Nanoparticles and Ascorbic Acid composition in the treatment of women with metabolic syndrome

Relevance of study. Metabolic syndrome (MS) increases the risk of atherosclerotic cardiovascular disease and type ІІ diabetes. Correction of the MS manifestations is important for reducing cardiovascular risk. Aim - to study the effects of using a composition consisting of quercetin (Q), polyvalent iron oxide nanoparticles (IONs) and ascorbic acid (AA) in women with MS. Materials and methods. 60 women with MS took part in the study. They were divided equally into two groups. The control group patients received a placebo for one month, and the main group received a composition of Q, IONs and AA for one month too. Anthropometric parameters, fasting plasma glucose level and standard oral glucose tolerance test (OGTT), serum lipid concentration, and microvascular endothelial function in a sample with reactive post-occlusion hyperemia were determined. Results. The use of the composition led to a decrease in the glycemia level of both on an empty stomach and after 2 hours of SGTT, the concentration of total cholesterol and low-density lipoproteins in blood serum in atherogenic dyslipidemia patients. At the same time, there was an improvement in the endothelium functional state of the microvessels, as evidenced by an increase in the maximum volume velocity of skin blood flow in the reactive hyperemia test. Conclusion. It was found that the use of a composition Q, IONs and AA had a positive effect on cardiovascular risk factors in MS patients. _________________________________________________________________________________________ Keywords: iron oxide nanoparticles; quercetin; metabolic syndrome; glucose and blood lipids; the microvascular endothelium function.

Evaluation of vasomotor dysfunction with a reduction of disease activity in patients with rheumatoid arthritis: a prospective study

Introduction. Endothelial dysfunction (ED) makes a significant contribution to the pathogenesis of rheumatoid arthritis (RA). However, changes of vasomotor function (VF) in patients with a reduction in disease activity have not been studied enough. Objective – to study VF changes in patients with RA and a reduce in disease activity, to clarify the role of RA serological profile and the presence of arterial hypertension (AH) in the formation of vasomotor dysfunction.Materials and methods. A total of 94 patients took part in the study (74 – the study group, 20 – the comparison group). The longitudinal study included 48 patients with 10 days interval between visits. RA activity reduced after prescribed anti-inflammatory therapy. All patients underwent laser Doppler flowmetry with functional tests (FT) to study VF. Also, the intensity of oxidative phosphorylation (IOP), levels of rheumatoid factor, antibodies to cyclic citrullinated peptide (ACCP) and antinuclear factor titer were assessed.Results. Correlations of ACCP with endothelial (EС), neurogenic (NС) and cardiac (CC) components of the amplitude-frequency spectrum were revealed. With a decrease in RA activity, an increase in CC and a decrease in the total tone of resistive vessels (TTRV) were observed. There was a tendency to improve the parameters of post-occlusive hyperemia (not statistically significant). The duration and area of the reaction after acetylcholine iontophoresis increased and IOP decreased. The presence of AH reduced EС and NС, worsened post-occlusive hyperemia, and was associated with the presence of factors for RA unfavourable course.Conclusion. The RA activity, the level of ACCP and the presence of AH make a significant contribution to the vasomotor dysfunction. At the same time, AH can be considered as a surrogate marker of an unfavourable course of RA. Endothelium-dependent regulation of blood flow, measured in FT, and IOP are closely related to disease activity. The reduce of RA activity was accompanied by a decrease in TTRV, confirming the leading role of the vasoconstriction in formation the ED pattern, the severity of ED will predominantly depend on the activity of the disease.

Microcirculation disorders in patients with severe COVID-19 and development of bacterial sepsis

It is believed that microcirculation dysfunction in sepsis primarily caused by damage of the endothelium by infectious agents and pro-inflammatory cytokines. Mechanisms of impaired microcirculation in the severe course of COVID-19 and sepsis likely to be similar. However, there are few reports studied microcirculation disorders in patients with COVID-19, and their results are sometimes contradictory. Objective. To assess the microcirculation of patients with severe Covid-19 and the development of bacterial sepsis using nail bed microscopy and laser Doppler flowmetry. Materials and methods. 16 intensive care unit COVID-19 patients subsequently diagnosed with bacterial sepsis were examined. Patients underwent vital capillaroscopy and an occlusive test using laser Doppler flowmetry. The average rate of capillary blood flow, the size of the perivascular zone, the density of capillaries, the presence of intravascular aggregates, the increase in the amplitude of the maximum post-occlusive blood flow and the average value of postocclusive blood flow relative to the initial one were valuated. Additionally, the level of serum proadrenomedullin was evaluated. Studies were performed on the day of admission and in dynamics. Results. By the capillaroscopy analysis, microcirculation disorders were detected in the form of a decrease in the linear speed of capillary blood flow (&lt;400 μm/s), an extention of the perivascular zone (&gt;100 μm), the circulation of microaggregates; the absence of postocclusive hyperemia was determined by an occlusive test. Secondary bacterial infection led to an even greater aggravation of microcirculation disorders: an increase of the perivascular zone, the progression of intravascular aggregation resulting in microthrombosis with a decrease of the density of the capillary network (according to capillaroscopy), as well as a sharp decrease of amplitude maximal increment of blood flow of post-осclusive circulation at the time of an occlusive sample. We also revealed a trend of negative correlation between the level of serum proadrenomedullin and the maximum increase in blood flow during the occlusive test. Conclusion. The secondary bacterial infection in patients with COVID-19 leads to a significant aggravation of microcirculation disorders with the development of perfusion deficiency and interstitial edema. The increased plasma proadrenomedullin level supports the concept of the significant role of endothelial dysfunction in the pathogenesis of severe COVID-10 and bacterial sepsis.

Correlation of Caesarean Section Rates to Maternal and Neonatal Mortality in the Eastern Mediterranean Region; A Population-Based Ecological Study

The physiological reaction of postocclusive local reactive hyperemia is regulated by neurovascular mechanisms and it reflects the function of microcirculation. Thermoregulatory changes occur first, in the form of increased skin surface temperature, which is usually followed by an increase in local blood flow. This study investigated a correlation between tourniquet duration on the upper arm, and the appearance of reactive hyperemia in the distal parts of the upper limb. Changes were registered with infrared thermometer and infrared thermography, which provided us a highly precise view of distribution of reactive hyperemia. Changes of oxygen saturation of peripheral arterial blood and blood pressure were also recorded. Our research has shown that longer duration of tourniquet leads to more intense and longer lasting reactive hyperemia in the palmar region, followed by higher temperatures of the skin surface, without any changes in postocclusive values of SpO2. Keywords: Infrared thermography, Microcirculation, Postocclusive hyperemia, Skin temperature, Tourniquet, Thermoregulatory changes.

Laser Speckle Contrast Analysis: Functional Evaluation of Microvascular Damage in Connective Tissue Diseases. Is There Evidence of Correlations With Organ Involvement, Such as Pulmonary Damage?

Laser speckle contrast analysis (LASCA) is a non-contact technique able to quantify peripheral blood perfusion (PBP) over large skin areas. LASCA has been used to study hand PBP in several clinical conditions. These include systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) and LASCA showed that PBP was significantly lower in these conditions than in healthy subjects (HS). Moreover, it has been demonstrated that LASCA is a safe technique also able to monitor digital ulcer perfusion and their evolution in SSc patients, during systemic and local treatment. The use of LASCA, coupled with reactivity tests is commonplace in the field of microvascular function research. Post-occlusive hyperemia reactivity (POHR) and local thermal hyperemia, associated with laser techniques are reliable tests in the evaluation of perfusion in SSc patients. Other studies used laser speckled techniques, together with acetylcholine and sodium nitroprusside iontophoresis, as specific tests of endothelium function. In conclusion, LASCA is a safe, non-contact reliable instrument for the quantification of PBP at skin level and can also be associated with reactivity tests to monitor disease progression and response to treatment in different connective tissue diseases.

Endothelial function and structural markers of atherosclerosis: relationship in old and senile age

Endothelial dysfunction (ED), intima-media thickness (IMT), and atherosclerotic plaques (ASPs) of the carotid arteries (CAs) are considered mutually associated markers of subclinical and clinical atherosclerosis. How true this statement is for older age groups remains unclear.Aim. To study the relationship of flow-dependent vasodilation (FDV) with CA IMT and ASPs in a population sample over 58 years old.Material and methods. The study was carried out in a population sample of men and women aged 58-82 years (Novosibirsk, HAPIEE project, n=788, 424 women). CA ultrasound was performed to assess IMT and ASPs. Endothelial function was assessed by postocclusive hyperemia ultrasound test; an increase in brachial artery initial diameter (FDV%) &lt;10% was regarded as ED.Results. The average IMT in men was 0,95 mm (SD 0,18) and was significantly higher than in women: 0,88 mm (SD 0,17), p&lt;0,001. The average FDV% values in men were 2,7% (SD 7,32), while in women — 3,2% (SD 7,19) and did not differ significantly by sex. The incidence of ED was 88,2% in men and 85,8% in women. There was no a significant linear relationship between FDV and IMT neither in men (β=-1,76, SD 2,25, p=0,436), nor in women (β=-2,19, SD 2,15, p=0,309). Also, there were no differences in average IMT and ASP frequency in the groups with and without ED among men and women. When divided into age groups, ED was associated with an increase in IMT only in women aged &lt;78 versus women without ED (p=0,047).Conclusion. In the population sample of 58-82 years old, mutual associations of subclinical markers of atherosclerosis (ED, IMT, ASP of CAs) have not been confirmed. Only in women aged &lt;78 years, ED was associated with an increase in IMT. The results obtained indicate that the treatment approaches proposed for young and middle-aged people may be less effective in old and senile age.

The Association between Foot and Ulcer Microcirculation Measured with Laser Speckle Contrast Imaging and Healing of Diabetic Foot Ulcers.

Diagnosis of peripheral artery disease in people with diabetes and a foot ulcer using current non-invasive blood pressure measurements is challenging. Laser speckle contrast imaging (LSCI) is a promising non-invasive technique to measure cutaneous microcirculation. This study investigated the association between microcirculation (measured with both LSCI and non-invasive blood pressure measurement) and healing of diabetic foot ulcers 12 and 26 weeks after measurement. We included sixty-one patients with a diabetic foot ulcer in this prospective, single-center, observational cohort-study. LSCI scans of the foot, ulcer, and ulcer edge were conducted, during baseline and post-occlusion hyperemia. Non-invasive blood pressure measurement included arm, foot, and toe pressures and associated indices. Healing was defined as complete re-epithelialization and scored at 12 and 26 weeks. We found no significant difference between patients with healed or non-healed foot ulcers for both types of measurements (p = 0.135–0.989). ROC curves demonstrated moderate sensitivity (range of 0.636–0.971) and specificity (range of 0.464–0.889), for LSCI and non-invasive blood pressure measurements. Therefore, no association between diabetic foot ulcer healing and LSCI-measured microcirculation or non-invasive blood pressure measurements was found. The healing tendency of diabetic foot ulcers is difficult to predict based on single measurements using current blood pressure measurements or LSCI.

756-P: Bromocriptine-QR (BQR) Ameliorates Immunocyte Pro-Oxidative Stress/Proinflammatory (POS/PI) and ER Stress Phenotype in T2DM Subjects

Background: Both CNS reduced dopaminergic and elevated sympathetic tone converge to stimulate a POS/PI phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2DM. BQR, a sympatholytic dopamine agonist for treatment of T2DM, improves postprandial dysglycemia and reduces CVD events.Aim: To examine the effect of BQR on POS/PI/ER stress phenotype of peripheral blood mononuclear (PBMN) cells in T2DM.Study Design: 15 T2DM subjects treated with a GLP-1 RA received BQR (3.2 mg/day) for 16 weeks. Endothelial function was measured by post-occlusion hyperemia. Postprandial glucose metabolism was assessed by meal tolerance test with the double tracer technique (Endo Diab Metab 2018:e00034). Blood PBMN cells were isolated and expression of genes (RT-qPCR) from the following cell physiologic systems was quantitated: (i) multiple-pathway antioxidant regulators that increase in response to systemic oxidative stress (OS); (ii) genes known to be expressed and operative in the ER stress response (including associated autophagy) (see Table for specific gene details).Results: See Table.Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and markedly attenuates the POS/PI/ER stress condition in plasma and PBMN cells of T2DM subjects, providing potential mechanisms for BQR’s CV protective effect.View largeDownload slideView largeDownload slide DisclosureM. Ezrokhi: Employee; Self; VeroScience LLC. A. H. Cincotta: Employee; Self; VeroScience LLC, Employee; Spouse/Partner; VeroScience LLC, Stock/Shareholder; Self; VeroScience LLC. E. Cersosimo: None. J. M. Adams: None. M. Alatrach: None. C. Agyin: None. C. L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Xeris Pharmaceuticals, Inc. N. Cominos: Employee; Self; VeroScience LLC. R. A. Defronzo: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk.

Endotheliumprotectiv and antihypoxic properties of quercetin in elderly patients with metabolic syndrome

Aim: To investigate the effectiveness of course quercetin in improving functional state of the microvascular endothelium and to determine the possibility of using quercetin to increase body resistance to hypoxia in the elderly. Materials and methods. The effectiveness of quercetin in improving the functional state of the endothelium and increasing body resistance to hypoxia was studied in 110 elderly patients with metabolic syndrome, who were divided equally into the main and control groups. Patients in the main group received quercetin at a daily dose of 240 mg for 3 months, and patients in the control group received placebo for the same period. Before and after treatment, the microvascular endothelial function was studied by laser Doppler flowmetry using the post-occlusive hyperemia test. Acute hypoxic test was performed under isocapnicnormobaric hypoxia, during which the followings were recorded: blood saturation (SpO2), heart rate and diastolic blood pressure (BP). Results. In the group of patients receiving quercetin, there was an improvement in blood flow to the skin, as evidenced by a statistically significant increase in the maximum volumetric rate of cutaneous blood flow and the duration of the recovery period of OSHSK to baseline in the post-occlusive hyperaemia. The course of quercetin also led to a less significant decrease in SpO2 during hypoxic test and to a decrease in the absolute values of systolic and diastolic blood pressure, while reducing an increase of the systolic blood pressure on the 20th min of the hypoxic test. Conclusions. In elderly patients with metabolic syndrome (within a 3 month course) the use of quercetin has improved the microvascular endothelium functional status and increased the resistance to hypoxia.

CAPILLARY DENSITY DURING POSTOCCLUSIVE REACTIVE HYPEREMIA AND VENOUS CONGESTION DETERIORATES WITH ADVANCING CKD STAGES

Objective: Cardiovascular disease is the main cause of mortality in CKD patients. Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video-capillaroscory provides a thorough assessment of capillary density and microcirculation changes. The aim of this study is to examine structural and functional capillary density in CKD patients of stages 2 to 4. Design and method: A total of 96 CKD patients were included in the study. The population consisted of 4 equal groups according to CKD stage (2, 3a, 3b and 4). All patients underwent nailfold video-capillaroscopy, during which capillary density was measured at baseline, after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase). Arterial stiffness and arterial wave parameters were measured with applanation tonometry and common carotid intima-media thickness (IMT) with a 2D ultrasound device. Results: Capillary density at baseline showed a progressive reduction with advancing CKD stages (stage 2: 32.63 ± 2.79, stage 3a: 31.23 ± 3.84, stage 3b: 32.48 ± 3.34, stage 4: 28.50 ± 3.09, p &lt; 0.001). Similar reductions were observed in capillary density during postocclusive hyperemia (39.42 ± 3.00, 37.63 ± 4.24, 38.35 ± 3.83, and 33.77 ± 3.34, respectively, p &lt; 0.001) and after venous congestion (41.10 ± 3.09, 39.02 ± 4.41, 39.90 ± 3.51, and 35.21 ± 3.40, p &lt; 0.001). Office pulse wave velocity showed a non-significant increasing trend with advancing CKD, but carotid IMT did not. In multivariate regression analysis, eGFR showed a positive association (per ml/min increase; OR: 0.053, 95%CI: 0.004 to 0.101), whereas diabetes (OR: -1.706, 95%CI: -3.176 to -0.236), and parathormone (PTH) (per pg/ml increase; OR: -0.022, 95%CI: -0.036 to -0.008) negative associations with post-occlusive capillary density. Conclusions: Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, the presence of diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may play a central role in the increased burden of cardiovascular events in CKD patients.

NAIL CAPILLARY DENSITY DURING POSTOCCLUSIVE REACTIVE HYPEREMIA AND VENOUS CONGESTION IS MORE IMPAIRED IN DIABETIC COMPARED TO NON-DIABETIC CKD PATIENTS

Objective: Alterations in endothelial function and capillary circulation have been associated with increased cardiovascular events and overall mortality. Both diabetes mellitus (DM) and chronic kidney disease (CKD) have been associated with microcirculatory damage. Nailfold video-capillaroscory can provide a thorough assessment of capillary density and microcirculation changes. This is the first study examining in comparison microcirculatory function parameters in diabetic and non-diabetic patients with CKD. Design and method: We included 48 diabetic and 48 non-diabetic adult patients (&gt;18 years) with CKD (eGFR: &lt; 90 and &gt; 15 mL/min/1.73m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase). Results: Baseline demographic, anthropometric and laboratory characteristics were similar between patients with and without diabetes in total and in CKD stages. Overall, no significant differences at baseline capillary density were observed between groups; however diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2, p = 0.022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2, p = 0.015). When stratified according to CKD stages, the between-group differences in parameters of interest were not significant in stages 2, 3a and 4. In stage 3b, capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline (31.1 ± 2.8 vs 33.4 ± 3.4 capillaries/mm2, p = 0.044), during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2, p = 0.037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2, p = 0.022). Conclusions: Capillary density during postocclusive reactive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory functional impairment in CKD. These differences are more prominent in CKD stage 3b, and less prominent in earlier and later stages.

The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease

Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non-diabetic CKD patients via nailfold video-capillaroscopy. We included 48 diabetic and 48 non-diabetic adult CKD patients. All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2-minute venous occlusion (congestion phase). Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3±3.8 vs 38.3±4.3 capillaries/mm2 , P=.022) and at venous congestion (37.8±4.0 vs 39.8±4.2 capillaries/mm2 , P=.015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline, during postocclusive hyperemia (36.8±2.7 vs 40.0±4.3 capillaries/mm2 , P=.037) and venous congestion (38.3±2.8 vs 41.5±3.5 capillaries/mm2 , P=.022). Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b.

Cutaneous microcirculation in patients with peripheral arterial occlusive disease: Comparison of capillary blood circulation in the nail fold of finger and toe.

In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area -was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries.

The improvement of the functional condition of micro-vascular endothelium among the aged people with metabolic syndrome under quercetin influence

Abstract. The Aim of study is the impact of course application of quercetin on the functional state of the endothelium of the microvessels in elderly people with metabolic syndrome. Materials and methods. We examined 110 patients (55 primary and 55 control patients) with metabolic syndrome (MS). Patients in the main group (n = 55) received quercetin ("Kvertin", chewing tablets manufactured by PJSC "Borshchagovsky KFZ", 80 mg 3 times a day) during 3 months. The control group patients (n = 55) received placebo tablets. The volume velocity of skin blood flow in the region of the middle third of the inner surface of the forearm was determined using the laser doppler flowmetry (LDP) on the apparatus BLF-21D (Transonic Systems Inc, USA). The functional state of the endothelium of microvessels was examined in a sample with post-exclusive hyperemia by clamping shoulder vessels of with a cuff for 3 minutes, in which the pressure exceeded the systolic blood pressure of the subject by 50 mm Hg. Blood pressure was measured by the Erkameter 3000 (Germany) mercury sphygmomanometer on the shoulder artery in accordance with ESH recommendations. Results. In the group of patients receiving quercetin, when performing a test with post-occlusive hyperemia, there was a statistically significant increase in the maximum volumetric velocity of the skin blood flow and the duration of the recovery period, the volumetric velocity of the skin blood flow to the initial level, which indicates an improvement in the vasomotor function of the microvessel endothelium. Improvement of the functional state of the endothelium occurred in 38 of 55 patients (69%) examined and was accompanied by a significant decrease in the level of systolic and diastolic blood pressure. Patients in the control group showed no improvement in the indices of vasomotor function of the microvessel endothelium. Conclusions. Course application of quercetin improves the functional state of the endothelium of microvessels, which helps to lower blood pressure in patients with metabolic syndrome. Key words: metabolic; syndrome; quercetin; functional state of the endothelium; arterial pressure

Microcirculatory function deteriorates with advancing stages of chronic kidney disease independently of arterial stiffness and atherosclerosis.

Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD). Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video capillaroscopy provides a thorough assessment of capillary density and functional reserve. This study aimed to examine possible differences in structural and functional capillary density in CKD stages 2-4 with nailfold video capillaroscopy. Ninety-six CKD patients, divided into four equally sized groups according to CKD stage (2, 3a, 3b, 4), underwent nailfold video capillaroscopy, during which capillary density was measured at baseline, after 4-min arterial occlusion and after 2-min venous occlusion. Arterial stiffness and wave parameters were measured with applanation tonometry and commoncarotid intima-media thickness (ccIMT) with ultrasound. Baseline capillary density showed a progressive reduction with advancing CKD stages (stage 2: 32.6 ± 2.8, stage 3a: 31.2 ± 3.8, stage 3b: 32.5 ± 3.3, stage 4: 28.5 ± 3.1, p = 0.011). Similar reductions were observed during postocclusive hyperemia (39.4 ± 3.0, 37.6 ± 4.2, 38.4 ± 3.8, and 33.8 ± 3.3, respectively; p = 0.021) and after venous congestion (41.1 ± 3.1, 39.0 ± 4.4, 39.9 ± 3.5, and 35.2 ± 3.4; p = 0.032). Office PWV and ccIMT showed nonsignificant increasing trends with advancing CKD. In multivariate analysis, eGFR showed a positive association (per ml/min increase; β: 0.053, 95% CI: 0.004-0.101), whereas diabetes (β: -1.706, 95% CI: -3.176 to -0.236) and parathyroid hormone (PTH) (per pg/ml increase; β: -0.022, 95% CI: -0.036 to -0.008) had negative associations with postocclusive capillary density. Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may largely contribute to the increased cardiovascular risk of CKD patients.

Evaluation Of Inter-rater And Test-retest Reliability For Near-infrared Spectroscopy Reactive Hyperemia Measures

Near-Infrared spectroscopy (NIRS) is a non-invasive tool used to measure blood flow in peripheral tissues. More information on test-retest reliability and inter-rater agreement of NIRS-based reperfusion assessments is needed. PURPOSE: To assess inter-rater agreement for NIRS based data analysis, and evaluate the measurement’s reliability across days. METHODS: On three separate days, participants’ (N=15 males, 22± 2 yr,) reactive hyperemia was measured in the left gastrocnemius muscle using Continuous-Wave NIRS. A blood pressure cuff was placed proximal to the knee and inflated to occlude lower leg blood flow for 5 minutes. The cuff was rapidly deflated, and the blood flow responses were measured until values returned to baseline. Raw NIRS data were exported and analyzed in a custom-written routine in MATLAB by two individuals. The following NIRS parameters were selected:(1) the time for the O2Hb signal to reach 50% peak post-occlusion hyperemia (T1/2), (2) The O2Hb range used to normalize the NIRS signal; (3) the post peak-hyperemic O2Hb recovery slope, taken as an index of sustained microvascular dilation. Inter-rater agreement was assessed using Intraclass Correlation Coefficients (ICC), calculated using an absolute agreement two-way mixed effects model. 95% confidence intervals (CI) of ICCs are reported. Cronbach’s alpha was used to assess day to day reliability for each of the measures. RESULTS: The ICC data indicate that there is “good” to “excellent” agreement between NIRS analyzers as shown in table 1.The Cronbach’s alpha for raters 1 and 2 were: T1/2 (α =.89, α = .91), O2Hb (α =.95, α = .89), and post peak-hyperemic O2Hb recovery slope (α =.74, α = .83). CONCLUSION: Our data indicate multiple raters can be used to analyze NIRS based reperfusion measures with good agreement and that the method has sufficient test-retest reliability to use in experimental designs involving multiple laboratory visits.