This study aims to investigate the changes in microcirculation and internal environment before sepsis in patients with infectious diseases.
Methods
In this single-center prospective observational study, all patients did not meet the diagnostic criteria of sepsis 3.0 at admission. Blood samples and sublingual microcirculation were collected at admission, 24 and 48 h after admission.
Results
A total of 101 patients completed this study. In total, 46 patients met the diagnostic criteria of sepsis 3.0 within 5 days after admission, while the remaining 55 patients did not. The platelet (PLT) was significantly lower in the sepsis patients (195.17 ± 63.89 vs. 242.02 ± 68.59, p = .01), Microvascular Flow Index (MFI) (2.45 ± 0.33 vs. 2.70 ± 0.18, p = .00) and Proportion of Perfused Vessels (PPV) (92.44 ± 4.45 vs. 95.88 ± 3.20, p = .00) were significantly lower, while Flow Heterogeneity Index (FHI) (0.32 ± 0.13 vs. 0.22 ± 0.10, p = .00) was significantly higher in the in the sepsis patients at admission. Decreased levels of MFI (p = .00, OR 0.02, 95% CI: 0.00, 0.15) and PLT (p = .00, OR 0.99, 95% CI: 0.98, 1.00) were independent risk factors for sepsis. Additionally, the 24 h PLT change rate (AUC 0.85, Cutoff −0.17, sensitivity 0.70, specificity 0.93, and Youden index 0.63) suggested a potential early warning effect for sepsis.
Conclusion
Changes in microcirculation disturbance and the internal environment occurred before sepsis. The MFI and PLT are independent risk factors for sepsis. Sublingual microcirculation and PLT deterioration can be used as early warning indicators before sepsis.
{"title":"Sublingual microcirculation and internal environment changes as early indications of sepsis: A prospective observational study","authors":"Yi Lu, Jun Yang, Peng Li, Fei Teng, Shubin Guo","doi":"10.1111/micc.12801","DOIUrl":"10.1111/micc.12801","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the changes in microcirculation and internal environment before sepsis in patients with infectious diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this single-center prospective observational study, all patients did not meet the diagnostic criteria of sepsis 3.0 at admission. Blood samples and sublingual microcirculation were collected at admission, 24 and 48 h after admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 101 patients completed this study. In total, 46 patients met the diagnostic criteria of sepsis 3.0 within 5 days after admission, while the remaining 55 patients did not. The platelet (PLT) was significantly lower in the sepsis patients (195.17 ± 63.89 vs. 242.02 ± 68.59, <i>p</i> = .01), Microvascular Flow Index (MFI) (2.45 ± 0.33 vs. 2.70 ± 0.18, <i>p</i> = .00) and Proportion of Perfused Vessels (PPV) (92.44 ± 4.45 vs. 95.88 ± 3.20, <i>p</i> = .00) were significantly lower, while Flow Heterogeneity Index (FHI) (0.32 ± 0.13 vs. 0.22 ± 0.10, <i>p</i> = .00) was significantly higher in the in the sepsis patients at admission. Decreased levels of MFI (<i>p</i> = .00, OR 0.02, 95% CI: 0.00, 0.15) and PLT (<i>p</i> = .00, OR 0.99, 95% CI: 0.98, 1.00) were independent risk factors for sepsis. Additionally, the 24 h PLT change rate (AUC 0.85, Cutoff −0.17, sensitivity 0.70, specificity 0.93, and Youden index 0.63) suggested a potential early warning effect for sepsis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Changes in microcirculation disturbance and the internal environment occurred before sepsis. The MFI and PLT are independent risk factors for sepsis. Sublingual microcirculation and PLT deterioration can be used as early warning indicators before sepsis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eli Sihn Samdal Steinskog, Kenneth Finne, Marianne Enger, Lars Helgeland, Per Ole Iversen, Emmet McCormack, Helge Wiig, Olav Tenstad
Background and aims
Acute myeloid leukemia (AML) is a heterogeneous malignant condition characterized by massive infiltration of poorly differentiated white blood cells in the blood stream, bone marrow, and extramedullary sites. During leukemic development, hepatosplenomegaly is expected to occur because large blood volumes are continuously filtered through these organs. We asked whether infiltration of leukemic blasts initiated a response that could be detected in the interstitial fluid phase of the spleen and liver.
Material and Methods
We used a rat model known to mimic human AML in growth characteristics and behavior. By cannulating efferent lymphatic vessels from the spleen and liver, we were able to monitor the response of the microenvironment during AML development.
Results and Discussion
Flow cytometric analysis of lymphocytes showed increased STAT3 and CREB signaling in spleen and depressed signaling in liver, and proteins related to these pathways were identified with a different profile in lymph and plasma in AML compared with control. Additionally, several proteins were differently regulated in the microenvironment of spleen and liver in AML when compared with control.
Conclusion
Interstitial fluid, and its surrogate efferent lymph, can be used to provide unique information about responses in AML-infiltered organs and substances released to the general circulation during leukemia development.
{"title":"Isolation of lymph shows dysregulation of STAT3 and CREB pathways in the spleen and liver during leukemia development in a rat model","authors":"Eli Sihn Samdal Steinskog, Kenneth Finne, Marianne Enger, Lars Helgeland, Per Ole Iversen, Emmet McCormack, Helge Wiig, Olav Tenstad","doi":"10.1111/micc.12800","DOIUrl":"10.1111/micc.12800","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and aims</h3>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is a heterogeneous malignant condition characterized by massive infiltration of poorly differentiated white blood cells in the blood stream, bone marrow, and extramedullary sites. During leukemic development, hepatosplenomegaly is expected to occur because large blood volumes are continuously filtered through these organs. We asked whether infiltration of leukemic blasts initiated a response that could be detected in the interstitial fluid phase of the spleen and liver.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>We used a rat model known to mimic human AML in growth characteristics and behavior. By cannulating efferent lymphatic vessels from the spleen and liver, we were able to monitor the response of the microenvironment during AML development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Discussion</h3>\u0000 \u0000 <p>Flow cytometric analysis of lymphocytes showed increased STAT3 and CREB signaling in spleen and depressed signaling in liver, and proteins related to these pathways were identified with a different profile in lymph and plasma in AML compared with control. Additionally, several proteins were differently regulated in the microenvironment of spleen and liver in AML when compared with control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Interstitial fluid, and its surrogate efferent lymph, can be used to provide unique information about responses in AML-infiltered organs and substances released to the general circulation during leukemia development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9434910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coronary microvascular dysfunction (CMD) is an important component of ischemic heart disease. Here, we assessed the associations between anxiety/depression and CMD using coronary microvascular function indicators.
Methods
The study included 81 patients (26 males and 55 females) with nonobstructive coronary artery disease. The symptoms of anxiety and depression were measured with Self-rating Anxiety Scale and Self-rating Depression Scale. Coronary microvascular function was assessed using coronary flow reserve (CFR) measured by transthoracic Doppler echocardiography.
Results
The anxiety group had significantly lower CFR than that in the no-anxiety group (2.97 ± 0.63 vs. 3.40 ± 0.61, p = .029). In bivariate correlation analysis, anxiety was negatively associated with CFR (r = −.333, p = .002). In the multiple linear regression model, after adjusting for age, sex, BMI, hypertension, dyslipidemia, smoking status, and family history of premature coronary heart disease, anxiety was negatively associated with CFR (β = −.314, p = .008). When both anxiety and depression were included in the multiple linear regression model, anxiety was also negatively associated with CFR (β = −.345, p = .012).
Conclusion
Anxiety patients had lower CFR, anxiety was independently associated with CFR. Psychological disorders may play an important role in coronary microvascular dysfunction.
目的冠状动脉微血管功能障碍是缺血性心脏病的重要组成部分。在这里，我们使用冠状动脉微血管功能指标评估焦虑/抑郁与CMD之间的关系。方法纳入非阻塞性冠状动脉疾病患者81例(男26例，女55例)。采用焦虑自评量表和抑郁自评量表对焦虑和抑郁症状进行测量。采用经胸多普勒超声心动图测量冠状动脉血流储备(CFR)评价冠状动脉微血管功能。结果焦虑组CFR明显低于无焦虑组(2.97±0.63∶3.40±0.61,p = 0.029)。在双变量相关分析中，焦虑与CFR呈负相关(r = -)。333, p = .002)。在多元线性回归模型中，在调整了年龄、性别、BMI、高血压、血脂异常、吸烟状况和早发冠心病家族史等因素后，焦虑与CFR呈负相关(β =−)。314, p = .008)。当多元线性回归模型中同时包含焦虑和抑郁时，焦虑也与CFR呈负相关(β =−)。345, p = .012)。结论焦虑患者CFR较低，焦虑与CFR独立相关。心理障碍可能在冠状动脉微血管功能障碍中起重要作用。
{"title":"Anxiety is associated with coronary microvascular dysfunction: Results from the CAMADA study","authors":"Ying Li, Weixian Xu, Lijun Guo","doi":"10.1111/micc.12798","DOIUrl":"10.1111/micc.12798","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Coronary microvascular dysfunction (CMD) is an important component of ischemic heart disease. Here, we assessed the associations between anxiety/depression and CMD using coronary microvascular function indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 81 patients (26 males and 55 females) with nonobstructive coronary artery disease. The symptoms of anxiety and depression were measured with Self-rating Anxiety Scale and Self-rating Depression Scale. Coronary microvascular function was assessed using coronary flow reserve (CFR) measured by transthoracic Doppler echocardiography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The anxiety group had significantly lower CFR than that in the no-anxiety group (2.97 ± 0.63 vs. 3.40 ± 0.61, <i>p</i> = .029). In bivariate correlation analysis, anxiety was negatively associated with CFR (<i>r</i> = −.333, <i>p</i> = .002). In the multiple linear regression model, after adjusting for age, sex, BMI, hypertension, dyslipidemia, smoking status, and family history of premature coronary heart disease, anxiety was negatively associated with CFR (<i>β</i> = −.314, <i>p</i> = .008). When both anxiety and depression were included in the multiple linear regression model, anxiety was also negatively associated with CFR (<i>β</i> = −.345, <i>p</i> = .012).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anxiety patients had lower CFR, anxiety was independently associated with CFR. Psychological disorders may play an important role in coronary microvascular dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9448678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John T. Nardini, Charles W. J. Pugh, Helen M. Byrne
Objective
Disease complications can alter vascular network morphology and disrupt tissue functioning. Microvascular diseases of the retina are assessed by visual inspection of retinal images, but this can be challenging when diseases exhibit silent symptoms or patients cannot attend in-person meetings. We examine the performance of machine learning algorithms in detecting microvascular disease when trained on statistical and topological summaries of segmented retinal vascular images.
Methods
We compute 13 separate descriptor vectors (5 statistical, 8 topological) to summarize the morphology of retinal vessel segmentation images and train support vector machines to predict each image's disease classification from the summary vectors. We assess the performance of each descriptor vector, using five-fold cross validation to estimate their accuracy. We apply these methods to four datasets that were assembled from four existing data repositories; three datasets contain segmented retinal vascular images from one of the repositories, whereas the fourth “All” dataset combines images from four repositories.
Results
Among the 13 total descriptor vectors considered, either a statistical Box-counting descriptor vector or a topological Flooding descriptor vector achieves the highest accuracy levels. On the combined “All” dataset, the Box-counting vector outperforms all other descriptors, including the topological Flooding vector which is sensitive to differences in the annotation styles between the different datasets.
Conclusion
Our work represents a first step to establishing which computational methods are most suitable for identifying microvascular disease and assessing their current limitations. These methods could be incorporated into automated disease assessment tools.
{"title":"Statistical and topological summaries aid disease detection for segmented retinal vascular images","authors":"John T. Nardini, Charles W. J. Pugh, Helen M. Byrne","doi":"10.1111/micc.12799","DOIUrl":"10.1111/micc.12799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Disease complications can alter vascular network morphology and disrupt tissue functioning. Microvascular diseases of the retina are assessed by visual inspection of retinal images, but this can be challenging when diseases exhibit silent symptoms or patients cannot attend in-person meetings. We examine the performance of machine learning algorithms in detecting microvascular disease when trained on statistical and topological summaries of segmented retinal vascular images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compute 13 separate descriptor vectors (5 statistical, 8 topological) to summarize the morphology of retinal vessel segmentation images and train support vector machines to predict each image's disease classification from the summary vectors. We assess the performance of each descriptor vector, using five-fold cross validation to estimate their accuracy. We apply these methods to four datasets that were assembled from four existing data repositories; three datasets contain segmented retinal vascular images from one of the repositories, whereas the fourth “All” dataset combines images from four repositories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 13 total descriptor vectors considered, either a statistical Box-counting descriptor vector or a topological Flooding descriptor vector achieves the highest accuracy levels. On the combined “All” dataset, the Box-counting vector outperforms all other descriptors, including the topological Flooding vector which is sensitive to differences in the annotation styles between the different datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our work represents a first step to establishing which computational methods are most suitable for identifying microvascular disease and assessing their current limitations. These methods could be incorporated into automated disease assessment tools.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9825606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunjie Zhang, Patrick Huber, Marc Praetner, Alice Zöllner, Lesca Holdt, Andrej Khandoga, Maximilian Lerchenberger
Objective
Post-hepatectomy liver failure (PHLF) is the main limitation of extended liver resection. The molecular mechanism and the role of leukocytes in the development of PHLF remain to be unveiled. We aimed to address the impact of serine proteases (SPs) on the acute phase after liver resection by intravitally analyzing leukocyte recruitment and changes in hemodynamics and microcirculation of the liver.
Methods
C57BL/6 mice undergoing 60% partial hepatectomy were treated with aprotinin (broad-spectrum SP inhibitor), tranexamic acid (plasmin inhibitor), or vehicle. Sham-operated animals served as controls. In vivo fluorescence microscopy was used to quantify leukocyte-endothelial interactions immediately after, as well as 120 min after partial hepatectomy in postsinusoidal venules, along with measurement of sinusoidal perfusion rate and postsinusoidal shear rate. Recruitment of leukocytes, neutrophils, T cells, and parameters of liver injury were assessed in tissue/blood samples.
Results
Leukocyte recruitment, sinusoidal perfusion failure rate, and shear rate were significantly increased in mice after 60% partial hepatectomy compared to sham-operated animals. The inhibition of SPs or plasmin significantly attenuated leukocyte recruitment and improved the perfusion rate in the remnant liver. ICAM-1 expression and neutrophil recruitment significantly increased after 60% partial hepatectomy and were strongly reduced by plasmin inhibition.
Conclusions
Endothelial activation and leukocyte recruitment in the liver in response to the increment of sinusoidal shear rate were hallmarks in the acute phase after liver resection. SPs mediated leukocyte recruitment and contributed to the impairment of sinusoidal perfusion in an ICAM-1-dependent manner in the acute phase after liver resection.
{"title":"Serine proteases mediate leukocyte recruitment and hepatic microvascular injury in the acute phase following extended hepatectomy","authors":"Yunjie Zhang, Patrick Huber, Marc Praetner, Alice Zöllner, Lesca Holdt, Andrej Khandoga, Maximilian Lerchenberger","doi":"10.1111/micc.12796","DOIUrl":"10.1111/micc.12796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Post-hepatectomy liver failure (PHLF) is the main limitation of extended liver resection. The molecular mechanism and the role of leukocytes in the development of PHLF remain to be unveiled. We aimed to address the impact of serine proteases (SPs) on the acute phase after liver resection by intravitally analyzing leukocyte recruitment and changes in hemodynamics and microcirculation of the liver.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C57BL/6 mice undergoing 60% partial hepatectomy were treated with aprotinin (broad-spectrum SP inhibitor), tranexamic acid (plasmin inhibitor), or vehicle. Sham-operated animals served as controls. In vivo fluorescence microscopy was used to quantify leukocyte-endothelial interactions immediately after, as well as 120 min after partial hepatectomy in postsinusoidal venules, along with measurement of sinusoidal perfusion rate and postsinusoidal shear rate. Recruitment of leukocytes, neutrophils, T cells, and parameters of liver injury were assessed in tissue/blood samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Leukocyte recruitment, sinusoidal perfusion failure rate, and shear rate were significantly increased in mice after 60% partial hepatectomy compared to sham-operated animals. The inhibition of SPs or plasmin significantly attenuated leukocyte recruitment and improved the perfusion rate in the remnant liver. ICAM-1 expression and neutrophil recruitment significantly increased after 60% partial hepatectomy and were strongly reduced by plasmin inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Endothelial activation and leukocyte recruitment in the liver in response to the increment of sinusoidal shear rate were hallmarks in the acute phase after liver resection. SPs mediated leukocyte recruitment and contributed to the impairment of sinusoidal perfusion in an ICAM-1-dependent manner in the acute phase after liver resection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10609667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endothelial cell (EC) coupling occurs through gap junctions and underlies cerebral blood flow regulation governed by inward-rectifying K+ (KIR) channels. This study addressed effects of KIR channel activity on EC coupling before and during Alzheimer's disease (AD).
Methods
Intact EC tubes (width: ~90–100 μm; length: ~0.5 mm) were freshly isolated from posterior cerebral arteries of young Pre-AD (1–3 months) and aged AD (13–18 months) male and female 3xTg-AD mice. Dual intracellular microelectrodes applied simultaneous current injections (±0.5–3 nA) and membrane potential (Vm) recordings in ECs at distance ~400 μm. Elevated extracellular potassium ([K+]E; 8–15 mmol/L; reference, 5 mmol/L) activated KIR channels.
Results
Conducted Vm (∆Vm) responses ranged from ~−30 to 30 mV in response to −3 to +3 nA (linear regression, R2 ≥ .99) while lacking rectification for charge polarity or axial direction of spread. Conduction slope decreased ~10%–20% during 15 mmol/L [K+]E in Pre-AD males and AD females. 15 mmol/L [K+]E decreased conduction by ~10%–20% at lower ∆Vm thresholds in AD animals (~±20 mV) versus Pre-AD (~±25 mV). AD increased conducted hyperpolarization by ~10%–15% during 8–12 mmol/L [K+]E.
Conclusions
Brain endothelial KIR channel activity modulates bidirectional spread of vasoreactive signals with enhanced regulation of EC coupling during AD pathology.
{"title":"KIR channel regulation of electrical conduction along cerebrovascular endothelium: Enhanced modulation during Alzheimer's disease","authors":"Md A. Hakim, Erik J. Behringer","doi":"10.1111/micc.12797","DOIUrl":"https://doi.org/10.1111/micc.12797","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Endothelial cell (EC) coupling occurs through gap junctions and underlies cerebral blood flow regulation governed by inward-rectifying K<sup>+</sup> (K<sub>IR</sub>) channels. This study addressed effects of K<sub>IR</sub> channel activity on EC coupling before and during Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intact EC tubes (width: ~90–100 μm; length: ~0.5 mm) were freshly isolated from posterior cerebral arteries of young Pre-AD (1–3 months) and aged AD (13–18 months) male and female <i>3xTg-AD</i> mice. Dual intracellular microelectrodes applied simultaneous current injections (±0.5–3 nA) and membrane potential (V<sub>m</sub>) recordings in ECs at distance ~400 μm. Elevated extracellular potassium ([K<sup>+</sup>]<sub>E</sub>; 8–15 mmol/L; reference, 5 mmol/L) activated K<sub>IR</sub> channels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Conducted V<sub>m</sub> (∆V<sub>m</sub>) responses ranged from ~−30 to 30 mV in response to −3 to +3 nA (linear regression, <i>R</i><sup>2</sup> ≥ .99) while lacking rectification for charge polarity or axial direction of spread. Conduction slope decreased ~10%–20% during 15 mmol/L [K<sup>+</sup>]<sub>E</sub> in Pre-AD males and AD females. 15 mmol/L [K<sup>+</sup>]<sub>E</sub> decreased conduction by ~10%–20% at lower ∆V<sub>m</sub> thresholds in AD animals (~±20 mV) versus Pre-AD (~±25 mV). AD increased conducted hyperpolarization by ~10%–15% during 8–12 mmol/L [K<sup>+</sup>]<sub>E</sub>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Brain endothelial K<sub>IR</sub> channel activity modulates bidirectional spread of vasoreactive signals with enhanced regulation of EC coupling during AD pathology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50146429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Goksel Guven, Annemieke Dijkstra, Tjallingius Martijn Kuijper, Nicole Trommel, Margriet Elisabeth van Baar, Arzu Topeli, Can Ince, Cornelis Hendrik van der Vlies
Objective
Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values.
Methods
Fifteen healthy volunteers (53% female, median age 29 [IQR 22–40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis.
Results
Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline.
Discussion
LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.
目的激光组织灌注监测技术已越来越多地应用于动物和人体研究中，以评估血流。然而，这些技术使用的是任意单位，关于它们的可比性的知识很少。本研究旨在模拟激光散斑对比成像(LSCI)和激光多普勒灌注成像(LDPI)之间的关系，用于测量大范围血流量值下的组织灌注。方法选取15名健康志愿者，其中女性53%，中位年龄29岁[IQR 22-40]。我们用硝普钠离子导入前臂，诱导局部血管舒张，增加皮肤血流量。此外，在对侧上臂进行逐步血管闭塞以减少血流量。采用线性混合模型分析对两种技术进行比较。结果LSCI测定的基线血通量值为33±6.5任意单位(AU)(变异系数[CV] = 20%)， LDPI测定的基线血通量值为60±11.5 AU (CV = 19%)。在离子透入方案结束时，局部血通量分别增加到LDPI和LSCI测量的基线的724±412%和259±87%。另一方面，在逐步血管闭塞试验中，LDPI和LSCI时的血通量分别下降到基线的212±40%和412±177%。与基线皮肤血流量相比，LSCI和LDPI仪器在血流量增加方面存在很强的相关性;然而，相对于基线，在血流量降低时相关性较弱。LSCI和LDPI仪器的血流量高于基线皮肤血流量呈高度线性;然而，当血流量低于基线时，相关性降低。这项研究的发现可能是在特定患者群体中使用LSCI的基础，例如烧伤护理。
{"title":"Comparison of laser speckle contrast imaging with laser Doppler perfusion imaging for tissue perfusion measurement","authors":"Goksel Guven, Annemieke Dijkstra, Tjallingius Martijn Kuijper, Nicole Trommel, Margriet Elisabeth van Baar, Arzu Topeli, Can Ince, Cornelis Hendrik van der Vlies","doi":"10.1111/micc.12795","DOIUrl":"10.1111/micc.12795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifteen healthy volunteers (53% female, median age 29 [IQR 22–40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/de/MICC-30-0.PMC10078364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9267280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadia Meyer, Katja Richter, Lars Brodowski, Constantin von Kaisenberg, Anette Melk, Bernhard Schmidt, Florian P. Limbourg, Bianca Schröder-Heurich, Frauke von Versen-Höynck
Objective
The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women.
Methods
Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models.
Results
Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability.
Conclusions
Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.
{"title":"Impairment of endothelial progenitor cells in women after kidney transplantation","authors":"Nadia Meyer, Katja Richter, Lars Brodowski, Constantin von Kaisenberg, Anette Melk, Bernhard Schmidt, Florian P. Limbourg, Bianca Schröder-Heurich, Frauke von Versen-Höynck","doi":"10.1111/micc.12794","DOIUrl":"10.1111/micc.12794","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10602334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.
{"title":"Engineered models of the lymphatic vascular system: Past, present, and future","authors":"Amirali Selahi, Abhishek Jain","doi":"10.1111/micc.12793","DOIUrl":"10.1111/micc.12793","url":null,"abstract":"<p>The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9427243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p < .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Pers
{"title":"Abstracts from the 47th Annual Meeting of Japanese Society for Microcirculation","authors":"","doi":"10.1111/micc.12784","DOIUrl":"10.1111/micc.12784","url":null,"abstract":"We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p < .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Pers","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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