Microvascular research最新文献

Background and aims: Systemic sclerosis (SSc) is a systemic autoimmune disease, characterized by widespread microvasculopathy and fibrosis. Vascular and endothelial cell changes appear to precede other features of SSc. Retinal vascular analysis is a new, easy-to-use tool for the assessment of retinal microvascular function. The primary aim of this study was to investigate whether retinal microcirculation is affected in patients with SSc compared to healthy controls.

Methods: Microvascular function was assessed non-invasively measuring flicker-light induced vasodilation of retinal arterioles (FIDart%). In addition, FID of retinal venules (FIDven%), central retinal arteriolar and venular equivalents (CRAE and CRVE), and measurements of flow-mediated vasodilation (FMD) of the brachial artery, pulse wave velocity (PWV) and pulse wave analysis were obtained. Patients with SSc were prospectively enrolled in the study (n = 40, mean age 56 ± 11 years, females 73 %) and compared with age- and sex-matched healthy controls (HC, n = 40; mean age 59 ± 15 years, females 73 %).

Results: Patients with SSc showed significant impairment of retinal microvascular function compared to age- and gender-matched HC (FIDart%: 2.23 ± 2.0 % vs. 3.1 ± 1.9 %, respectively, p = 0.04). FMD and PWV were not significantly different between the groups. Impaired retinal microvascular function was associated with SSc disease duration.

Conclusion: Our study shows a significant impairment of retinal microvascular function in patients with SSc. Because this association seems to be independent of CV risk and dependent on disease duration, retinal vessel analysis may have the potential to serve as a tool for risk assessment and prognosis.

Background: Diabetes mellitus (DM) is a metabolic abnormality affecting 537 million people worldwide. Poor glycemic control, longer duration, and poor medication adherence increased the risk of DM complications. Comprehensive evidence on the pooled prevalence of microvascular complications in DM patients in Ethiopia is not available. Furthermore, individual study findings for the prevalence of microvascular complications in DM patients, and associated factors were not consistent.

Objective: This systemic review and meta-analysis aimed to assess the pooled prevalence of microvascular complications in DM patients, and its associated risk factors in Ethiopia.

Methods: Systematic search on Scopus, PubMed, Science Direct electronic database, Google Scholar search engine, and library registration was used to identify relevant studies following reviews and meta-analysis guidelines. Microsoft Excel spreadsheets were used to extract data, and Extracted data was analyzed using STATA software version 17.0. A Sensitivity analysis was conducted to assess the role of each study in the final result and the presence of publication bias was assessed by Egger's test. Heterogeneity across studies was checked by Cochran's Q statistic and I2 statistics and significant heterogeneity was assessed using subgroup analysis.

Results: The pooled prevalence of microvascular complications in DM patients was 32.89 % (95 % CI: 28.17-37.60). In addition, the pooled prevalence of retinopathy, neuropathy, and nephropathy in DM patients was 17.16 % (95 % CI: 12-22 %), 10.49 % (95 % CI: 8-13 %) and 11.52 % (95 % CI: 9-15 %) respectively. Age >60 years old (AOR = 1.08 (95%CI = 1.02-1.15), longer duration of DM (AOR = 1.57 (95 % CI = 1.31-1.84), poor glycemic control (AOR = 2.21 (95 % CI = 1.52-2.91), poor adherence to diabetic medications (AOR = 3.61 (95 % CI = 1.83-5.38) and presence of hypertension (AOR = 2.26 (95 % CI = 1.73-2.80) ware associated risk factors for microvascular complications in DM patients.

Concussion: Around one-third of DM patients had one or more microvascular complications. Patients with advanced age, longer duration of DM, poor glycemic control, poor medication adherence, and comorbidity like hypertension should be targeted to tackle the occurrence and severity of microvascular complications in DM patients.

Protocol registration: The review protocol was developed and was registered with PROSPERO registration number (CRD42023486459).

Although the mouse mesenteric artery is widely used as a model of resistance vessels, it is unknown which order branch is the best representative and if there is a heterogeneity of vascular activity in different orders. We systematically compared the vasorelaxation between the mouse mesenteric artery's first- and second-order branches. The first- and second-order branches of the mesenteric artery (lumen diameter of >300 μm and 179.9 ± 11.1 μm, respectively) were taken from the location close to their branching points in wide-type (WT) and TRPV4^-/- (KO) mice. Vasorelaxation of the mesenteric artery was measured using a Danish DMT520A microvascular system. Acetylcholine (ACh) induced much greater vasorelaxation via TRPV4 channels/endothelium-dependent hyperpolarization (EDH/H₂S) in the second-order branch. The store-operated Ca²⁺ entry (SOCE) mediated much greater vasorelaxation via EDH in the second-order branch than that via NO in the first-order branch. However, capsaicin-induced vasorelaxation was much greater via TRPV1/NO and TRPV1/CGRP in the first-order branch than TRPV4/EDH only in the second-order branch. Moreover, sex differences in ACh-induced vasorelaxation were obviously in the first-order branch but marginally in the second-order branch. Mechanistically, the myoendothelial gap junction (MEGJ) is involved in ACh-induced vasorelaxation in the second-order branch but not in the first-order branch. However, endothelial IK_Ca and SK_Ca functions and endothelium-independent vasorelaxation were similar for both first- and second-order branches. TRPV1/NO/CGRP mediates endothelium-dependent vasorelaxation in the first-order branch as the best representative of conduit vessels, but TRPV4/EDH/H₂S mediates endothelium-dependent vasorelaxation in the second-order branch as the best representative of resistance vessels in mice.

Background: Excess fluid in the interstitium can adversely affect the microcirculation. We studied how gradual dilution of the blood plasma by crystalloid fluid influences microcirculatory variables and capillary filtration in 20 patients undergoing surgery.

Methods: Video recordings of the sublingual mucosal were made on four occasions during the surgery and compared with quasi-measurements of the capillary filtration rate using retrospective volume kinetic data collected over 5-10-minute periods during 262 infusion experiments with crystalloid fluid.

Results: The number of crossings (vessel density) increased up to plasma dilution of 15-20 % whereafter it decreased. The proportion of the vessels that were perfused (PPV) decreased and reached a nadir of -15 % at a dilution of 20-30 %. Changes in the number of crossings and the PPV correlated (r = 0.62, P < 0.001) but the curve was displaced so that crossings showed no change when PPV had decreased by approximately 10 %. However, the PPV of vessels with a thickness of ≤25 μm increased or remained constant in the dilution range of up to 20 %. The volume kinetic analysis showed that the capillary filtration was greater than expected from proportionality with the volume expansion up to a plasma dilution of 15 %, the greatest difference (+89 %) being for plasma dilution up to 5 %.

Conclusion: Plasma dilution of up to 15 % increased the vessel density, and the capillary filtration increased by more than suggested by the volume expansion. Dilution >15 % had a negative influence on these variables.

Background: Blood flow restriction caused by peripheral arterial disease (PAD) is reflected in reduced walking capacity. The peripheral mechanisms that may affect the walking capacity of individuals with PAD are not yet fully understood. This study aimed to 1) compare tissue oxygenation and muscle metabolism of individuals with PAD with different walking capacities and 2) evaluate which variables have the greatest potential to explain the variability in distance walked between performance levels.

Methods: The sample composed of adults diagnosed with PAD underwent evaluation of microvascular function in the gastrocnemius muscle through Near-Infrared Spectroscopy (NIRS) at two time points: (1) during the arterial occlusion maneuver; (2) on a treadmill test with constant speed and inclination (3.2 km/h, 10 %). The following NIRS parameters were selected: (1) percentage of peripheral tissue oxygen saturation (StO₂); (2) StO₂ delta; (3) reoxygenation rate; (4) time to reach lowest StO₂; (5) ischemia resistance time; (6) StO₂ in reactive hyperemia. Participants were divided into tertiles (T1, T2, and T3) according to the walking distance in the treadmill test. One-way analysis of variance (ANOVA) was used for comparisons between tertiles and multiple linear regression was used for association analyses.

Results: There were no significant differences between tertiles in baseline values or delta StO₂. The reoxygenation rate and StO₂ in hyperemia of the occlusion maneuver, as well as the time to reach the lowest StO₂ and the ischemia resistance time in the treadmill test, were significantly higher in T3 than in T1 and T2 (p < 0.05). Linear regression demonstrated that the ischemia resistance time is the variable that appears to have the greatest influence on the distance walked (adjusted R² = 0.83).

Conclusion: Better walking performance was associated with better dynamic response capacity to ischemia. Factors such as microvascular, endothelial, and muscular dysfunction appear to be decisive in reducing the walking capacity of individuals with PAD.

Vasculature of the small bowel mucosa, with a significant role in nutrient absorption and gut homeostasis, has been suggested to undergo remodeling in various gastrointestinal disorders, including celiac disease. However, due to its spatial organization within the mucosa, conventional 2D histological methods are of limited value in studying the intestinal vasculature reliably. X-ray microtomography (micro-CT) is a promising tool for soft tissue imaging, as it enables digital 3D reconstruction of various tissue samples, including endoscopically obtained small-bowel mucosal biopsies. In this proof-of-concept study, we utilize micro-CT imaging combined with iodine staining in revealing the 3D mucosal microvascular structures using celiac disease as a model. Furthermore, we present a unique image analysis workflow that enables the quantification of the microvascular network with explanatory parameters in untreated and treated celiac disease patients as well as in non-celiac disease controls. The calculation of these parameters has been unachievable previously using 2D image processing methods. The workflow produced results that showed noticeable differences in the microvascular structures from the point of diagnosis to after treatment. This unique method has potential to be used with various intestinal diseases and other applications where the mucosal vascular structures need to be visualized.

Intestinal ischemia-reperfusion (I/R) injury occurs under various surgical or disease conditions, where tissue hypoxia followed by reoxygenation results in the production of oxygen radicals and inflammatory mediators. These substances can target the endothelial barrier, leading to microvascular leakage. In this study, we induced intestinal I/R injury in mice by occluding the superior mesenteric artery, followed by removing the clamp to resume blood circulation. We assessed microvascular permeability to plasma proteins in vivo using intravital microscopy, measuring the time-dependent tracer distribution in the intravascular versus extravascular space in the mouse mesentery. Additionally, we examined endothelial cell-cell adhesive barrier resistance and junction morphology in cultured endothelial cell monolayers. At the molecular level, FAK inhibition similarly inhibited endothelial junction opening and barrier dysfunction in response to hydrogen peroxide-induced oxidative stress. To further investigate FAK's role with tissue/cell specificity, we developed an endothelial-specific inducible FAK knockout mouse model by crossbreeding FAK-floxed (FAK^fl/fl) mice with Tie-2-CreER^T2 transgenic mice. Compared to their wild-type controls, endothelial-specific FAK-deficient mice showed a blunted microvascular hyperpermeability response following I/R injury in the gut. Overall, our study demonstrates that FAK plays a significant signaling role in mediating endothelial barrier dysfunction and microvascular leakage during ischemia-reperfusion injury.

Introduction: Little is known about the day-to-day variability of different skin microcirculation parameters, and how this variability is influenced by age and sex. The aim was to examine the day-to-day variability of microcirculatory parameters in relation to age and sex.

Methods: The cutaneous microcirculation was measured using a fiber optic probe integrating laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) to measure oxygen saturation, red blood cell (RBC) tissue fraction, speed-resolved and conventional perfusion. Measurements at two separate days were compared during baseline, a 5-min occlusion and during the following post-occlusive reactive hyperemia (PORH) period on the volar forearm and dorsal foot in totally 48 men and women aged 20-30 and 50-60 years, respectively. Variability was expressed as the coefficient of variation CV and repeatability as the intraclass correlation coefficient ICC.

Results: Peak oxygen saturation during PORH had the lowest day-to-day variability for the forearm (CV = 2.1 %) and the foot (CV = 3.8 %) as well as an excellent repeatability (ICC = 0.80 and ICC = 0.82, respectively). Older women had a higher day-to-day variability in baseline conventional perfusion compared to younger women on the forearm (p = 0.007). On the foot, older women had a lower day-to-day variability than younger women for baseline oxygen saturation (p = 0.006) and peak RBC tissue concentration (p = 0.008). Older men had a lower day-to-day variability than younger men for baseline oxygen saturation (p = 0.012) but a higher variability for baseline and peak RBC tissue concentration (p = 0.008 and p = 0.002) on the foot.

Conclusion: Peak oxygen saturation had the lowest day-to-day variability of the measured parameters. A lower value of peak oxygen saturation has previously been associated with increasing systematic coronary risk implying that this is a suitable parameter for measuring microcirculatory dysfunction. Sex and age only affected the day-to-day variability of very few parameters.