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Microvascular Research[JOURNAL]

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Increase in endothelial microparticles is negatively correlated with decrease in renal microperfusion in septic rats.

Guo X, Liu J, Duan M

Microvasc Res · 2025 Jul · PMID 40187486 · Publisher ↗

INTRODUCTION: Endothelial dysfunction is an important pathophysiological mechanism of septic acute kidney injury, and endothelial microparticles (EMPs) can directly reflect the endothelial damage. However, the relationsh... INTRODUCTION: Endothelial dysfunction is an important pathophysiological mechanism of septic acute kidney injury, and endothelial microparticles (EMPs) can directly reflect the endothelial damage. However, the relationship between EMPs and renal microperfusion remains unclear. In this study, contrast-enhanced ultrasound (CEUS) imaging and side-stream dark field imaging were used to evaluate the renal microcirculatory perfusion in septic rats. METHODS: A cecal ligation and puncture model was established for inducing septic kidney injury in Sprague-Dawley rats. Later, the changes in mean arterial pressure (MAP), lactate level, renal artery blood flow (RBF) and mean renal artery velocity were measured. Flow cytometry was conducted to measure EMPs, CEUS imaging was performed to evaluate cortical and medullary perfusion enhancement, and side-stream dark-field imaging was carried out to detect the perfused small vessel density (PVD) and microvascular flow index of the renal cortex. RESULTS: In the sepsis group, EMPs and lactate levels increased at 12 h, macrohemodynamics (MAP and RBF) did not change, and the mean artery velocity (547.76 ± 28.40 mm/s) increased compared with the sham group (421.78 ± 34.58 mm/s). Meanwhile, cortical peak echointensity (PE), medullary PE, PVD, and microvascular flow index (MFI) decreased at 12 h. The decreases in pulsatility index (PI) and resistance index (RI) suggested the damage of vascular appearance. The pathological results revealed erythrocyte stasis in the capillaries. At 24 h, macrodynamics decreased compared with that at 12 h. The EMPs and lactate levels reached a peak at 24 h. Glomerular vascular endothelium was locally thickened. Moreover, EMPs were negatively correlated with the decreased renal microcirculatory perfusion. CONCLUSIONS: This study shows that endothelial microparticles (EMPs) are closely associated with renal microcirculatory dysfunction in septic acute kidney injury (S-AKI). CEUS can sensitively reflect changes in renal microperfusion, providing earlier indications of kidney injury compared to macrocirculatory changes, and holds potential for early diagnosis of S-AKI.

K channel inhibition-induced hyporemia in skeletal muscle: No evidence for pre-capillary sphincter action.

Schulze KM, Hirai DM, Colburn TD … +3 more , Craig JC, Musch TI, Poole DC

Microvasc Res · 2025 Jul · PMID 40164381 · Full text

INTRODUCTION: Whether pre-capillary sphincters are present and regulate red blood cell (RBC) flux at the individual capillary level, especially in skeletal muscle, is controversial. Recently, blockade of K channels using... INTRODUCTION: Whether pre-capillary sphincters are present and regulate red blood cell (RBC) flux at the individual capillary level, especially in skeletal muscle, is controversial. Recently, blockade of K channels using the sulphonylurea glibenclamide (GLI) was demonstrated to reduce muscle blood flow and lower vascular conductance. The present investigation tested the hypothesis that, if pre-capillary sphincters were involved in GLI-induced blood flow reductions, a defined luminal narrowing would be evident in the proximate region of the capillaries. METHODS: Videomicroscopy of the spinotrapezius capillary bed was performed under control (Krebs-Henseleit) and GLI (200 μM in Krebs-Henseleit) superfusion. Capillary RBC flux was measured within individual capillaries and their luminal diameter was measured using a calibrated digital ruler at the branch-point and subsequently downstream. RESULTS: GLI reduced capillary RBC flux by 31% (p = 0.004). Despite the presence of a reduced RBC flux, no detectable reduction or, indeed, any change in capillary luminal diameter was present at any measurement site. The average diameter at the branching point was 4.9 ± 0.3 μm, and at 5, 10, 20 and 50 μm downstream, the average diameters were 4.8 ± 0.4, 4.8 ± 0.5, 5.0 ± 0.7, and 5.2 ± 0.4 μm, respectively and were unchanged by GLI (all P > 0.05). CONCLUSIONS: Accordingly, the absence of any evidence for capillary luminal narrowing or constriction in these data support that the GLI-induced reductions in capillary RBC flux and muscle blood flow occur via upstream effects within the arteriolar bed. Decreases in skeletal muscle microcirculatory RBC flux with this K channel blocker were not regulated by any detectable capillary structural alterations.

Lymphatics in the chick embryo chorioallantoic membrane.

Ribatti D

Microvasc Res · 2025 Jul · PMID 40120145 · Publisher ↗

The chick embryo chorioallantoic membrane (CAM) has been used as an experimental in vivo model to study angiogenesis and anti-angiogenesis. Moreover, due to the lack of a fully developed immunocompetent system, the CAM i... The chick embryo chorioallantoic membrane (CAM) has been used as an experimental in vivo model to study angiogenesis and anti-angiogenesis. Moreover, due to the lack of a fully developed immunocompetent system, the CAM is suitable to study various aspects of tumor angiogenesis and metastatic potential. In this article, we emphasize the important role of the CAM also in the study of lymphangiogenesis and tumor lymphangiogenesis in vivo. This experimental model is more advantageous than other assays because it is a relatively simple, quick, and low-cost. Finally, it does not require administrative procedures to obtain ethics committee approval for animal experimentation.

Interplay between platelet and T lymphocyte after coronary artery bypass grafting (CABG): Evidence for platelet mediated post-CABG immunomodulation.

Farhid F, Hosseini E, Kargar F … +1 more , Ghasemzadeh M

Microvasc Res · 2025 Jul · PMID 40107494 · Publisher ↗

BACKGROUND: On-pump coronary artery bypass grafting (CABG) triggers inflammatory responses as a result of surgical stress and extracorporeal circulation, which affect platelet and leukocyte activation while enhancing the... BACKGROUND: On-pump coronary artery bypass grafting (CABG) triggers inflammatory responses as a result of surgical stress and extracorporeal circulation, which affect platelet and leukocyte activation while enhancing their intimate crosstalk. Given this, the study presented here aimed to investigate platelet-T cell interaction after CABG focusing on the changes in immunomodulatory subtypes of regulatory T Cells. METHODS: Blood samples were obtained from twenty patients undergoing on-pump CABG at 5 different time points of 24 h before, immediately, 2 h, 24 h, and one week after surgery. Total leukocyte and lymphocyte counts were determined using an automatic cell counter. Platelet P-selectin expression, frequencies of CD4 and CD8 T cells, platelet-T cell aggregates (PTCAs), and regulatory T cells derived from CD4 (T4reg) and CD8 (T8reg) cells, were assessed by flow cytometry. RESULTS: A significant increase in total leukocyte count occurred immediately after CABG, whereas, conversely, lymphocyte and CD4 T cells but not CD8 T cells decreased 2 h after surgery. However, all these changes returned to pre-CABG baseline levels within a week. Platelet P-selectin expression increased immediately after surgery, followed by a two-hour delay after PTCA, and both returned to baseline after one week. T4regs and T8regs showed a similar increase and decrease trend, where T8regs but not T4regs returned to baseline one week after surgery. CONCLUSION: CABG surgery induces an inflammatory response that activates platelets and enhances P-selectin expression, facilitating PTCA formation. This mechanism is critical for the dynamics and differentiation of T cells, which play an essential role in post-CABG modulation of immune responses.

Plasma neutrophil gelatinase-associated lipocalin level as a predictor of atherosclerotic cardiovascular disease risk in patients undergoing catheterization.

Mayyas F

Microvasc Res · 2025 May · PMID 40010663 · Publisher ↗

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVDs) represent a global health burden contributing to substantial morbidity and mortality. The neutrophil gelatinase-associated lipocalin (NGAL), a small glycoprote... BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVDs) represent a global health burden contributing to substantial morbidity and mortality. The neutrophil gelatinase-associated lipocalin (NGAL), a small glycoprotein, is secreted by inflammatory neutrophils, macrophages, and dendritic cells, playing a role in inflammation. However, its relevance as a predictor of ASCVDs risk across patients from low to very high-risk, and correlation with the need for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) remains largely unexplored. Our objective was to assess plasma NGAl levels in patients with low to very high risk of ASCVD and their relationship with the severity of CAD and the requirement for revascularization. METHODS: Outpatients and patients undergoing catheterization were categorized into low, moderate, high, and very high risk of ASCVD. Plasma levels of NGAL were measured using ELISA and analyzed in relation to CAD status and the need for revascularization by PCI or CABG. RESULTS: Plasma NGAl levels were elevated in CAD patients, with higher levels in patients with acute coronary syndrome compared to those with stable angina. A gradual increase in plasma NGAl levels was noted with the elevated risk of ASCVD and degree of coronary artery stenosis. Notably, plasma NGAl level was independently correlated with ASCVD risk and the need for revascularization by PCI. CONCLUSION: Our study indicates that plasma NGAl levels are linked to the risk of ASCVD and may help predict the development and severity of CAD. Further research targeting NGAL could explore its potential to mitigate the risk of ASCVD.

Imaging the microvasculature using nailfold capillaroscopy in patients with coronavirus disease-2019; A cross-sectional study.

Wilkinson S, Wilkinson J, Grace A … +14 more , Lyon D, Mellor M, Yunus T, Manning J, Dinsdale G, Berks M, Knight S, Bakerly N, Gebril A, Dark P, Herrick A, Taylor C, Dickinson M, Murray A

Microvasc Res · 2025 May · PMID 39961398 · Publisher ↗

OBJECTIVES: It is understood that microvascular dysfunction plays a key role in the pathogenesis of SARS-CoV-2 coronavirus disease (COVID-19). The aim of this study was to evaluate the usefulness of an automated, quantit... OBJECTIVES: It is understood that microvascular dysfunction plays a key role in the pathogenesis of SARS-CoV-2 coronavirus disease (COVID-19). The aim of this study was to evaluate the usefulness of an automated, quantitative nailfold capillaroscopy system in identifying microvascular changes in those confirmed with or having had COVID-19. METHODS: Ninety-seven participants were enrolled into this study and grouped as follows: 52 participants with acute COVID-19 (further grouped by disease severity) and 45 participants with convalescent COVID-19 (further grouped into long COVID i.e. symptoms beyond 12 weeks, and fully recovered). Nailfold capillaroscopy images were obtained from the bilateral ring fingers using a Dino-Lite CapillaryScope 200 Pro, a small USB handheld microscope. Images were assessed quantitatively using bespoke automated measurement software and the number of haemorrhages noted for each participant. RESULTS: Capillaries were predominantly 'normal' in appearance with narrow capillary loops and evenly distributed, but with an increased number of haemorrhages (40 % in the convalescent group and 17 % in the acute group, p = 0.007). There was no statistically significant difference in the mean width of capillaries (20.9-21.8 μm) or vessel density (9.6-9.9 caps/mm; acute and convalescent group, respectively). CONCLUSIONS: This study has demonstrated the feasibility of nailfold capillaroscopy at the critical care bedside. Capillary structure appeared normal across all groups of individuals affected by COVID-19. Although the small differences in the microvasculature in recovered patients compared to in acutely unwell patients may suggest delayed structural change due to COVID-19, these differences are unlikely to be clinically relevant. Longitudinal studies would be required to explore this in more detail.

Alternate local skin cooling and heating ameliorates impaired forearm skin vasodilation function mediated by prolonged sitting.

Tomita Y, Tagawa K, Nishiyasu T … +1 more , Fujii N

Microvasc Res · 2025 May · PMID 39954719 · Publisher ↗

Prolonged sitting can impair physiological functions. We hypothesized that prolonged sitting attenuates forearm cutaneous vascular function but alternating local skin cooling and heating mitigates this attenuation. Eleve... Prolonged sitting can impair physiological functions. We hypothesized that prolonged sitting attenuates forearm cutaneous vascular function but alternating local skin cooling and heating mitigates this attenuation. Eleven young adults (five women) sat for 75 min in thermoneutral condition (25 °C) during which skin temperature at four forearm skin sites was modulated: 1) maintained at 33 °C (control), 2) reduced to 15 °C for 4 min, then rised to 40 °C, repeated 5 times, 3) maintained at 33 °C for 4 min, then rised to 40 °C for 4 min, repeated 5 times or 4) elevated to 40 °C. Before and after 75-min prolonged sitting, venoarteriolar reflex (VAR) was assessed by a reduction in cutaneous blood flow (laser Doppler flowmetry) mediated by venous occlusion, whereas post-occlusive reactive hyperemia (PORH) was assessed by increases in cutaneous blood flow following arterial occlusion. After prolonged sitting, PORH decreased at the control (mean with 95%CI: 40.2 [34.5, 45.9] %max vs. 26.3 [19.3, 33.3] %max P < 0.001), but this response was not seen at the site subjected to alternating 15 °C cooling and 40 °C heating (P = 0.983). VAR remained unchanged before and after prolonged sitting at the control (P = 0.990), but increased with 15 °C cooling and 40 °C heating (-47.8 [-61.6, -34.1] %baseline vs. -68.0 [-75.3, -60.7] %baseline P = 0.029). We show that prolonged sitting decreases forearm cutaneous vasodilation function (PORH), but this response is mitigated by alternating local skin cooling and heating. Additionally, prolonged sitting does not affect forearm cutaneous VAR, but alternating local skin cooling and heating enhances VAR.

Novel 2D/3D vascular biomarkers reveal association between fundus changes and coronary heart disease.

Dong X, Zou Y, Li X … +6 more , Su N, Wen Y, Fang J, Li X, Chen Q, Wang J

Microvasc Res · 2025 May · PMID 39938713 · Publisher ↗

PURPOSE: To compare structural and vascular differences in the macular region of the retina using optical coherence tomography (OCT)/OCT angiography (OCTA) between coronary angiography (CAG)-confirmed coronary heart dise... PURPOSE: To compare structural and vascular differences in the macular region of the retina using optical coherence tomography (OCT)/OCT angiography (OCTA) between coronary angiography (CAG)-confirmed coronary heart disease (CHD) patients and non-CHD individuals. METHODS: The study included 340 eyes from 180 CHD patients and 136 eyes from 68 controls. Imaging was conducted using the AngioVue OCT device with a macula-centered 6 mm ∗ 6 mm field of view. Retinal thickness and 2D/3D vascular-related biomarkers were derived using existing retinal layer segmentation software, and our previously proposed 2D/3D vascular and 3D foveal avascular zone segmentation methods. Statistical analyses included t-tests, Mann-Whitney U tests, chi-square tests, and Pearson's correlation. RESULTS: The CHD group exhibited significantly lower retinal nerve fiber layer (RNFL) thickness (r = -0.20, P < 0.001) in the inner inferior (I) region, based on macular region layer segmentation. For the 3D OCT images, as defined by the ETDRS grid, both the inner and outer retina layers in the outer superior (out-S) region were significantly thinner in the CHD group. The CHD group showed significantly lower overall 2D fractal dimension (FD) (1.72 ± 0.03 vs. 1.73 ± 0.02, P < 0.001) and vessel skeleton density (VSD) (26.61 ± 4.52 vs. 28.50 ± 3.40, P < 0.001) compared to the control group. The proposed 3D vascular density (VD) feature showed a significant difference between the groups (19.23 ± 5.67 vs. 20.69 ± 5.15, P = 0.048). CONCLUSION: Thinning of retinal thickness and reduced vascular density are associated with CHD and may serve as valuable, cost-effective biomarkers for assessing coronary artery disease assessment.

Transplantation of autologous endothelial progenitor cells promotes the repair of fusiform aneurysms.

Zhang L, Ni S, Zhang W … +6 more , Shi J, Ding J, Xu X, Zhang S, Zhang Y, Jiang T

Microvasc Res · 2025 May · PMID 39923840 · Publisher ↗

Endothelial progenitor cells (EPCs), which are precursors for endothelial cells, possess the capability of repairing vascular damage and predicting the extent of early vascular injury. However, the role of EPCs in the re... Endothelial progenitor cells (EPCs), which are precursors for endothelial cells, possess the capability of repairing vascular damage and predicting the extent of early vascular injury. However, the role of EPCs in the repair of fusiform aneurysms is not clear. Here, we constructed a fusiform aneurysm model using pancreatic elastase digestion and validated the improvement effect of EPCs through histological staining and immunofluorescence. HE staining and elastic fiber staining showed destruction of the tunica adventitia in the fusiform aneurysm, marked dilatation of the arterial lumen, and thinning of the elastic lamina in the fusiform aneurysm. In the fusiform aneurysm group, the concentration of vascular endothelial growth factor (VEGF) was notably decreased compared to both the control and the saline group. The level of EPCs in the peripheral blood was decreased in the model group. Transplantation of EPCs into fusiform aneurysms promoted vascular repair, indicated by the decrease of myeloperoxidase (MPO), advanced oxidation protein products (AOPP), matrix metalloproteinase-9 (MMP-9), platelet factor 4 (PF4), and Fe. The level of VEGF was also elevated after EPCs transplantation. Finally, we noted a marked rise in lactate level in the peripheral blood of fusiform aneurysms. Lactate treatment led to an elevation of H3K18la levels in EPCs and inhibited cell proliferation. In conclusion, this study discovered that in mice with fusiform aneurysms, elevated lactate levels in the peripheral blood trigger histone lactylation, such impeding the proliferation of EPCs. Transplantation of EPCs into fusiform aneurysms facilitated aneurysm repair. These findings lay the groundwork for EPCs in the treatment of fusiform aneurysms.

Feasibility of a method for measurement of retinal pulse-propagated wave velocity in humans.

Tang Z, Felder AE, Shahidi M

Microvasc Res · 2025 May · PMID 39922483 · Full text

Blood flow regulation has been shown to be compromised in common ocular diseases, such as diabetic retinopathy and glaucoma. The capacity of the retinal vessels to regulate blood flow can potentially serve as an oculomic... Blood flow regulation has been shown to be compromised in common ocular diseases, such as diabetic retinopathy and glaucoma. The capacity of the retinal vessels to regulate blood flow can potentially serve as an oculomics biomarker for evaluating ocular and systemic diseases. Pulse-propagated intravascular pressure waves cause deformations of the vessel walls, thus offering a means to interrogate vascular compliance. The purpose of the current study is to report a method for measuring retinal pulse-propagated wave velocity (rPWV) based on spectral analysis of pulsatile intensity waveforms in human circumpapillary retinal vasculature. Arterial and venous rPWV values, as well as inter-subject variabilities of rPWV in non-diabetic and diabetic subjects, are reported. Preliminary results demonstrated the feasibility of this method for measuring rPWV and its potential for assessment of vascular plasticity in response to blood flow changes due to ocular and systemic diseases.

Focal adhesion kinase mediates microvascular leakage and endothelial barrier dysfunction in ischemia-reperfusion injury.

Patrick R, Pando BD, Yang C … +6 more , Aponte A, Wang F, Ewing T, Ma Y, Yuan SY, Wu MH

Microvasc Res · 2025 May · PMID 39884384 · Full text

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. Th... 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) mice with Tie-2-CreER 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.

Sex and age-related day-to-day variability in the skin microcirculation during post-occlusive reactive hyperemia.

Richter F, Nilsson M, Henricson J … +5 more , Östgren CJ, Larsson M, Strömberg T, Fredriksson I, Iredahl F

Microvasc Res · 2025 May · PMID 39837458 · Publisher ↗

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 mi... 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.

X-ray microtomography imaging enables accurate visualization and quantification of the small-intestinal villi microvasculature - celiac disease as a model.

Reunamo A, Hannula M, Virta J … +3 more , Kurppa K, Lindfors K, Hyttinen J

Microvasc Res · 2025 Mar · PMID 39800235 · Publisher ↗

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... 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.

Low-grade hemodilution improves the microcirculatory function in surgical patients.

Hahn RG, Tlapakova K, Koudelova H … +4 more , Knoblochova V, Rehak D, Cerny V, Astapenko D

Microvasc Res · 2025 Mar · PMID 39740739 · Publisher ↗

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 filtrat... 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.

Prevalence of microvascular complications and associated factors among diabetes mellitus patients in Ethiopia: Systematic review and meta-analysis.

Kumie G, Nigatie M, Alamrew A … +21 more , Gedifie S, Kassahun W, Jemal A, Mulugeta C, Ayana S, Ayele M, Shitie E, Gtsadik B, Abebe W, Ashagre A, Misganaw T, Dejazmach Z, Sisay A, Asmare Z, Gashaw M, Getachew E, Gashaw Y, Tadesse S, Abate BB, Kidie AA, Reta MA

Microvasc Res · 2025 Mar · PMID 39732433 · Publisher ↗

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. Comprehe... 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).

Retinal microvascular dysfunction in systemic sclerosis.

Laptseva N, Bitos K, Rossi VA … +8 more , Nebunu D, Haider T, Nägele MP, Mihai C, Distler O, Ruschitzka F, Sudano I, Flammer AJ

Microvasc Res · 2025 Mar · PMID 39708913 · Publisher ↗

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. R... 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.

Muscle tissue oxygenation in individuals with peripheral arterial disease of different walking abilities: An exploratory study.

Przybysz GMP, Geisel PP, de Oliveira Nascimento I … +3 more , Monteiro DP, Pedrosa R, Pereira DAG

Microvasc Res · 2025 Mar · PMID 39667525 · Publisher ↗

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... 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 (StO); (2) StO delta; (3) reoxygenation rate; (4) time to reach lowest StO; (5) ischemia resistance time; (6) StO 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 StO. The reoxygenation rate and StO in hyperemia of the occlusion maneuver, as well as the time to reach the lowest StO 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 R = 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.

Functional heterogeneity of endothelium-dependent vasorelaxation in different order branches of mesenteric artery in female/male mice.

Zhang L, Rong S, Dong H

Microvasc Res · 2025 Mar · PMID 39613183 · Publisher ↗

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.... 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/HS) in the second-order branch. The store-operated Ca 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 and SK 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/HS mediates endothelium-dependent vasorelaxation in the second-order branch as the best representative of resistance vessels in mice.

Pulse wave analysis as a tool to assess endothelial function following lipid lowering intervention in hypercholesterolemia.

Ibrahim NNIN, Rasool AHG, Rahman RA … +2 more , Azlan M, Aziz AA

Microvasc Res · 2025 Mar · PMID 39586372 · Publisher ↗

BACKGROUND: Pulse wave analysis (PWA) assesses endothelial dependent vasodilation (EDV) via the change in augmentation index (AIx) and has been used as a tool to assess endothelial function. However, its effectiveness in... BACKGROUND: Pulse wave analysis (PWA) assesses endothelial dependent vasodilation (EDV) via the change in augmentation index (AIx) and has been used as a tool to assess endothelial function. However, its effectiveness in assessing the response to lipid lowering treatment has not been evaluated. The study aimed to describe and correlate the change in EDV following lipid lowering intervention in patients with hypercholesterolemia. METHODS: 48 newly diagnosed patients with hypercholesterolemia underwent 6 months intervention with statin and/or therapeutic lifestyle changes (TLC) in clinical setting. Lipid profile measurement and endothelial function assessment using PWA were performed pre- and post-intervention. RESULTS: Significant reductions in low density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and total cholesterol (TC) with corresponding significant improvement in EDV (2.94 ± 3.69 % to 7.50 ± 3.79 %, p < 0.001) were observed following intervention. Sub-analyses revealed greater LDL-C reductions and EDV improvements in the statin group compared to TLC. There was a significant inverse correlation between the change in EDV and the change in LDL-C after intervention (r = -0.298, p = 0.040). CONCLUSION: Endothelial function assessed by PWA showed a parallel change with lipid profile pattern following lipid lowering intervention. The simple and non-invasive method may provide a potential tool for evaluating endothelial function and treatment outcomes in patients with hypercholesterolemia.
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