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ELife Jul 2023Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying...
Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.
Topics: Animals; Mice; Microcirculation; Aging; Cognitive Dysfunction; White Matter; Cognition; Cerebral Cortex
PubMed: 37402178
DOI: 10.7554/eLife.86329 -
Eye (London, England) Jul 2022To investigate retinal perfusion by optical coherence tomography (OCT)-angiography and choroidal vascular features using an OCT-based image binarization method in...
PURPOSE
To investigate retinal perfusion by optical coherence tomography (OCT)-angiography and choroidal vascular features using an OCT-based image binarization method in patients with Behçet's disease (BD) without clinical ocular involvement.
METHODS
This study included 38 patients with non-ocular BD and 35 healthy participants. Macular region was evaluated with OCT-angiography (Optovue, Inc., Fremont, CA). A 6.0 × 6.0 mm rectanglescan centred on the fovea was used to record the scans. The enhanced depth imaging OCT scans (Heidelberg Eye Explorer version 1.8.6.0; Heidelberg Engineering) of the macula and peripapillary scans of the optic nerve head were binarized using ImageJ software (National Institutes of Health, Bethesda, MD, USA). The luminal area (LA), stromal area (SA), total choroidal area (TCA), and choroidal thickness (CT) were analysed. The choroidal vascularity index (CVI) was calculated as the ratio of the LA to the TCA.
RESULTS
Vessel density values of the superficial and deep macular capillary plexus were similar between the two groups (all p > 0.05). There was no significant difference between the groups in terms of the CT and TCA values in the macula and in all peripapillary sectors (all p > 0.05). However, the macula and temporal, nasal, and inferior sectors of the peripapillary area had significantly lower CVI values in the BD group compared with controls (p = 0.009, p = 0.002, p = 0.010, and p = 0.008, respectively).
CONCLUSIONS
Retinal microperfusion deficit was not observed in non-ocular Behçet patients. CVI may be a more robust marker than CT to indicate choroidal perfusion. A reduced CVI may suggest subclinical ocular involvement and choroidal ischemia in these patients.
Topics: Behcet Syndrome; Choroid; Humans; Microcirculation; Retina; Tomography, Optical Coherence
PubMed: 35115719
DOI: 10.1038/s41433-022-01932-8 -
American Journal of Respiratory and... Nov 2022
Topics: Humans; Shock, Cardiogenic; Microcirculation; Prospective Studies; Hemodynamics; Oxygen
PubMed: 35976803
DOI: 10.1164/rccm.202208-1523ED -
Critical Care Medicine Jul 2023This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow... (Observational Study)
Observational Study
OBJECTIVES
This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow alteration and outcome in critically ill patients.
DESIGN
Prospective, observational, pilot study.
SETTING
ICU in a university hospital.
PATIENTS
Two hundred eighty-two critically ill adult patients admitted to the ICU.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
All patients underwent simultaneous measurements by CRT and sidestream dark field imaging within 24 hours of ICU admission. Other clinical data such as demographic characteristics, hemodynamics, laboratory values, treatment, and physiologic parameters were also included simultaneously. Microcirculatory measurements were performed at 10.2 ± 5.7 hours after ICU admission. Of the 282 included patients, 106 (37.6%) were female, the median (interquartile range) age was 63 years (53-74 yr), and the median Sequential Organ Failure Assessment (SOFA) score was 5 (2-7). The primary finding was the association between CRT and simultaneous the condition of peripheral circulation (microvascular flow index [MFI]: r = -0.4430, p < 0.001; proportion of perfused vessels: r = -0.3708, p < 0.001; heterogeneity index: r = 0.4378, p < 0.001; perfused vessel density: r = -0.1835, p = 0.0020; except total vessel density: p = 0.9641; and De Backer score: p = 0.5202) in critically ill patients. In addition, this relationship was also maintained in subgroups. Microcirculatory flow abnormalities, 28-day mortality, and SOFA score appeared to be more severe for increasing CRT. In a multivariable analysis, prolonged CRT was independently associated with microvascular flow abnormalities (MFI < 2.6; odds ratio [OR], 1.608; 95% CI, 2.1-10.2; p < 0.001). Similarly, multivariable analysis identified CRT as an independent predictor of 28-day mortality (OR, 1.296; 95% CI, 1.078-1.558; p = 0.006).
CONCLUSIONS
In our ICU population, a single-spot prolonged CRT was independently associated with abnormal microcirculation and increased mortality.
Topics: Adult; Humans; Female; Middle Aged; Male; Microcirculation; Prospective Studies; Critical Illness; Pilot Projects; Mouth Floor; Hemodynamics; Intensive Care Units
PubMed: 36942969
DOI: 10.1097/CCM.0000000000005851 -
BMC Anesthesiology Dec 2019The endothelial glycocalyx (EG) is the thin sugar-based lining on the apical surface of endothelial cells. It has been linked to the physiological functioning of the... (Review)
Review
The endothelial glycocalyx (EG) is the thin sugar-based lining on the apical surface of endothelial cells. It has been linked to the physiological functioning of the microcirculation and has been found to be damaged in critical illness and after acute care surgery. This review aims to describe the role of EG in severely injured patients undergoing surgery, discuss specific situations (e.G. major trauma, hemorrhagic shock, trauma induced coagulopathy) as well as specific interventions commonly applied in these patients (e.g. fluid therapy, transfusion) and specific drugs related to perioperative medicine with regard to their impact on EG.EG in acute care surgery is exposed to damage due to tissue trauma, inflammation, oxidative stress and inadequate fluid therapy. Even though some interventions (transfusion of plasma, human serum albumin, hydrocortisone, sevoflurane) are described as potentially EG protective there is still no specific treatment for EG protection and recovery in clinical medicine.The most important principle to be adopted in routine clinical practice at present is to acknowledge the fragile structure of the EG and avoid further damage which is potentially related to worsened clinical outcome.
Topics: Anesthesiology; Endothelial Cells; Glycocalyx; Humans; Microcirculation; Perioperative Care; Surgical Procedures, Operative
PubMed: 31862008
DOI: 10.1186/s12871-019-0896-2 -
Critical Care (London, England) Mar 2024Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of... (Review)
Review
Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microcirculatory dysfunction in sepsis, there is a need for effective strategies to protect the endothelium. In this review we will discuss key mechanisms and putative therapeutic agents relevant to endothelial barrier function.
Topics: Humans; Microcirculation; Sepsis; Endothelium; Endothelium, Vascular
PubMed: 38521954
DOI: 10.1186/s13054-024-04875-6 -
Pancreas Sep 2020Pancreatic microcirculation has an essential role in orchestrating pancreatic homeostasis. Inherent complexity and technological limitation lead to interobserver...
OBJECTIVES
Pancreatic microcirculation has an essential role in orchestrating pancreatic homeostasis. Inherent complexity and technological limitation lead to interobserver variability and 1-sided microcirculatory data. Here, we introduce a multimodal device and computer algorithm-based platform for monitoring and visualizing integrated pancreatic microcirculation profiles.
METHODS
After anesthetizing and exposing pancreas tissue of BALB/c mice, probes of Oxygen to See, Microx TX3, and MoorVMS-LDF2 were positioned at pancreas in situ to capture the pancreatic microcirculatory oxygen (hemoglobin oxygen saturation, relative amount of hemoglobin, and partial oxygen pressure) and microhemodynamic data (microvascular blood perfusion and velocity). To assess and visualize pancreatic microcirculation profiles, raw data of pancreatic microcirculation profiles were processed and transformed using interquartile range and min-max normalization by Python and Apache ECharts.
RESULTS
The multimodal device-based platform was established and 3-dimensional microcirculatory modules were constructed. Raw data sets of pancreatic microcirculatory oxygen and microhemodynamic were collected. The outlier of data set was adjusted to the boundary value and raw data set was preprocessed. Normalized pancreatic microcirculation profiles were integrated into the 3-dimensional histogram and scatter modules, respectively. The 3-dimensional modules of pancreatic microcirculation profiles were then generated.
CONCLUSIONS
We established a multimodal device and computer algorithm-based monitoring platform for visualizing integrated pancreatic microcirculation profiles.
Topics: Algorithms; Animals; Diagnostic Techniques, Cardiovascular; Equipment Design; Hemodynamics; Humans; Imaging, Three-Dimensional; Male; Mice, Inbred BALB C; Microcirculation; Models, Cardiovascular; Oxygen; Pancreas; Time Factors
PubMed: 32769856
DOI: 10.1097/MPA.0000000000001627 -
JACC. Heart Failure Aug 2021Diabetes promotes the development of both heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction through diverse mechanisms,... (Review)
Review
Diabetes promotes the development of both heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction through diverse mechanisms, which are likely mediated through hyperinsulinemia rather than hyperglycemia. Diabetes promotes nutrient surplus signaling (through Akt and mammalian target of rapamycin complex 1) and inhibits nutrient deprivation signaling (through sirtuin-1 and its downstream effectors); this suppresses autophagy and promotes endoplasmic reticulum and oxidative stress and mitochondrial dysfunction, thereby undermining the health of diabetic cardiomyocytes. The hyperinsulinemia of diabetes may also activate sodium-hydrogen exchangers in cardiomyocytes (leading to injury and loss) and in the proximal renal tubules (leading to sodium retention). Diabetes may cause epicardial adipose tissue expansion, and the resulting secretion of proinflammatory adipocytokines onto the adjoining myocardium can lead to coronary microcirculatory dysfunction and myocardial inflammation and fibrosis. Interestingly, sodium-glucose cotransporter 2 (SGLT2) inhibitors-the only class of antidiabetic medication that reduces serious heart failure events-may act to mitigate each of these mechanisms. SGLT2 inhibitors up-regulate sirtuin-1 and its downstream effectors and autophagic flux, thus explaining the actions of these drugs to reduce oxidative stress, normalize mitochondrial structure and function, and mute proinflammatory pathways in the stressed myocardium. Inhibition of SGLT2 may also lead to a reduction in the activity of sodium-hydrogen exchangers in the kidney (leading to diuresis) and in the heart (attenuating the development of cardiac hypertrophy and systolic dysfunction). Finally, SGLT2 inhibitors reduce the mass and mute the adverse biology of epicardial adipose tissue (and reduce the secretion of leptin), thus explaining the capacity of these drugs to mitigate myocardial inflammation, microcirculatory dysfunction, and fibrosis, and improve ventricular filling dynamics. The pathophysiological mechanisms by which SGLT2 inhibitors may benefit heart failure likely differ depending on ejection fraction, but each represents interference with distinct pathways by which hyperinsulinemia may adversely affect cardiac structure and function.
Topics: Diabetes Mellitus; Heart Failure; Humans; Microcirculation; Myocytes, Cardiac; Stroke Volume
PubMed: 34325884
DOI: 10.1016/j.jchf.2021.05.019 -
Frontiers in Immunology 2022Autoimmune diseases are diseases that cause damage to the body's own tissues as a result of immune dysfunction, often involving multiple organs and systems. The heart is... (Review)
Review
Autoimmune diseases are diseases that cause damage to the body's own tissues as a result of immune dysfunction, often involving multiple organs and systems. The heart is one of the common target organs of autoimmune diseases. The whole structure of the heart can be affected, causing microcirculatory disorders, arrhythmias, pericardial damage, myocarditis, myocardial fibrosis, and impaired valvular function. However, early clinical manifestations of autoimmune heart damage are often overlooked because they are insidious or have no typical features. The damage is often severe and irreversible when symptoms are apparent, even life-threatening. Therefore, early detection and treatment of heart damage in autoimmune diseases is particularly important. Herein, we review the clinical features and mechanisms of cardiac damage in common rheumatic diseases.
Topics: Humans; Microcirculation; Autoimmune Diseases; Heart Injuries
PubMed: 36483559
DOI: 10.3389/fimmu.2022.1056400 -
Frontiers in Immunology 2021In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (HS)...
INTRODUCTION
In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (HS) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous HS, improves intestinal and hepatic microcirculation and mitochondrial function K(ATP)-channels in sepsis.
METHODS
In 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg i.p., 2: glibenclamide (GL) 5 mg • kg i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn's multiple comparison test (mitochondria). p < 0.05 was considered significant.
RESULTS
STS increased µHbO (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO and µflow (µHbO 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered.
CONCLUSION
The beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent.
Topics: Animals; Antioxidants; Colon; Disease Models, Animal; Liver; Male; Microcirculation; Mitochondria; Rats; Rats, Wistar; Sepsis; Thiosulfates
PubMed: 34163476
DOI: 10.3389/fimmu.2021.671935