Belt electrode-skeletal muscle electrical stimulation (B-SES) improves muscle strength, mass, and exercise tolerance. However, its effects on skeletal muscle microvascular responsiveness remain unclear. In this study, we investigated the acute effects of a single B-SES session on gastrocnemius microvascular responsiveness in healthy young men.
Methods
In this randomized crossover study, 12 healthy young men (mean age: 20.8 ± 1.0 years) underwent two 20-min conditions: electrical stimulation at the sensory threshold (Sham, n = 12) and at the maximum intensity not causing discomfort (B-SES, n = 12). Gastrocnemius metabolic rate (tissue oxygen saturation [StO2] downslope) and microvascular reperfusion rate (StO2 upslope) were assessed using near-infrared spectroscopy and a vascular occlusion test.
Results
In the B-SES condition, the StO2 downslope significantly steepened (Pre: −0.15 ± 0.03 %·s−1, Post: −0.20 ± 0.03 %·s−1, p = 0.002). The StO2 upslope also significantly steepened (Pre: 1.58 ± 0.52 %·s−1, Post: 2.56 ± 0.71 %·s−1, p < 0.001). A significant negative correlation was observed between the StO2 downslope and StO2 upslope (r = −0.581, p = 0.047). No significant changes were observed in the Sham condition.
Conclusions
A single B-SES session applied to the lower extremity significantly increased gastrocnemius metabolic rate and was associated with enhanced microvascular reperfusion. These findings suggest B-SES may be a useful therapeutic approach to improving microvascular responsiveness, particularly in individuals with limited exercise capacity.
目的:带状电极-骨骼肌电刺激(B-SES)可以提高肌肉力量、质量和运动耐受性。然而,其对骨骼肌微血管反应性的影响尚不清楚。在这项研究中,我们调查了单次B-SES对健康年轻男性腓肠肌微血管反应性的急性影响。方法在这项随机交叉研究中,12名健康年轻男性(平均年龄:20.8±1.0岁)接受了两种20分钟的条件:感觉阈值电刺激(Sham, n = 12)和不引起不适的最大强度电刺激(B-SES, n = 12)。采用近红外光谱和血管闭塞试验评估腓肠肌代谢率(组织氧饱和度[StO2]下坡)和微血管再灌注率(StO2上坡)。结果在B-SES条件下,StO2下坡明显变陡(Pre:−0.15±0.03%·s−1,Post:−0.20±0.03%·s−1,p = 0.002)。StO2上坡也显著变陡(Pre: 1.58±0.52%·s−1,Post: 2.56±0.71%·s−1,p <;0.001)。StO2下坡与StO2上坡呈显著负相关(r = - 0.581, p = 0.047)。假手术组未见明显变化。结论下肢单次B-SES治疗可显著提高腓肠肌代谢率,微血管再灌注增强。这些发现表明,B-SES可能是改善微血管反应性的有效治疗方法,特别是对于运动能力有限的个体。
{"title":"Acute effects of belt electrode-skeletal muscle electrical stimulation on microvascular responsiveness of the gastrocnemius muscle in healthy young men","authors":"Hajime Tamiya , Hina Kawashiri , Toshiaki Miyamoto , Yuko Kurosawa , Takafumi Hamaoka , Atsuhiro Tsubaki","doi":"10.1016/j.mvr.2025.104840","DOIUrl":"10.1016/j.mvr.2025.104840","url":null,"abstract":"<div><h3>Purpose</h3><div>Belt electrode-skeletal muscle electrical stimulation (B-SES) improves muscle strength, mass, and exercise tolerance. However, its effects on skeletal muscle microvascular responsiveness remain unclear. In this study, we investigated the acute effects of a single B-SES session on gastrocnemius microvascular responsiveness in healthy young men.</div></div><div><h3>Methods</h3><div>In this randomized crossover study, 12 healthy young men (mean age: 20.8 ± 1.0 years) underwent two 20-min conditions: electrical stimulation at the sensory threshold (Sham, <em>n</em> = 12) and at the maximum intensity not causing discomfort (B-SES, n = 12). Gastrocnemius metabolic rate (tissue oxygen saturation [StO<sub>2</sub>] downslope) and microvascular reperfusion rate (StO<sub>2</sub> upslope) were assessed using near-infrared spectroscopy and a vascular occlusion test.</div></div><div><h3>Results</h3><div>In the B-SES condition, the StO<sub>2</sub> downslope significantly steepened (Pre: −0.15 ± 0.03 %·s<sup>−1</sup>, Post: −0.20 ± 0.03 %·s<sup>−1</sup>, <em>p</em> = 0.002). The StO<sub>2</sub> upslope also significantly steepened (Pre: 1.58 ± 0.52 %·s<sup>−1</sup>, Post: 2.56 ± 0.71 %·s<sup>−1</sup>, <em>p</em> < 0.001). A significant negative correlation was observed between the StO<sub>2</sub> downslope and StO<sub>2</sub> upslope (<em>r</em> = −0.581, <em>p</em> = 0.047). No significant changes were observed in the Sham condition.</div></div><div><h3>Conclusions</h3><div>A single B-SES session applied to the lower extremity significantly increased gastrocnemius metabolic rate and was associated with enhanced microvascular reperfusion. These findings suggest B-SES may be a useful therapeutic approach to improving microvascular responsiveness, particularly in individuals with limited exercise capacity.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104840"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595548","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}
Pub Date : 2025-09-01Epub Date: 2025-07-02DOI: 10.1016/j.mvr.2025.104835
Simone Woodruff , Benjamin Zimmerman , Kevin J. Elk , Jennifer E. Jenks , Danica Bojovic , Anusha Mishra
Ex vivo imaging in acute cortical brain slices is a valuable tool to assess neurovascular coupling and is particularly useful for studying active, local changes in microvascular compartments in isolation from upstream or downstream changes in flow. However, the lack of vascular perfusion pressure ex vivo results in loss of vascular tone, which must be restored prior to experiments to unmask dilatory signals. The thromboxane A2 receptor agonist U46619 is a widely used preconstrictor, yet its dose-response properties and kinetics of action on different vascular segments are not fully known. Here, we characterize the effects of U46619 on cortical arterioles and capillaries in ex vivo slices from rats and mice. Dose response curves tested in acute rat brain slices using 0 to 1000 nM U46619 showed that maximal constriction is reached at ∼300 nM in both arterioles and capillaries. Extended application of 200 nM U46619 (∼66 % maximal dose) over 2 h revealed that, on average, capillaries constrict faster than arterioles in rat brain slices. Cross-species examination in mouse tissue showed that vessels in mouse brain slices respond faster and constrict stronger on average than in rat brain slices, and that mouse capillaries also constrict faster than mouse arterioles. Our observations suggest that near-maximal preconstriction can be achieved in ex vivo experiments using 200–300 nM U46619, with a minimum incubation time of 20 min for studies involving capillaries and at least 30 min for studies involving arterioles.
{"title":"Kinetics of thromboxane A2 receptor-driven vascular tone in the cerebral cortex ex vivo","authors":"Simone Woodruff , Benjamin Zimmerman , Kevin J. Elk , Jennifer E. Jenks , Danica Bojovic , Anusha Mishra","doi":"10.1016/j.mvr.2025.104835","DOIUrl":"10.1016/j.mvr.2025.104835","url":null,"abstract":"<div><div><em>Ex vivo</em> imaging in acute cortical brain slices is a valuable tool to assess neurovascular coupling and is particularly useful for studying active, local changes in microvascular compartments in isolation from upstream or downstream changes in flow. However, the lack of vascular perfusion pressure <em>ex vivo</em> results in loss of vascular tone, which must be restored prior to experiments to unmask dilatory signals. The thromboxane A2 receptor agonist U46619 is a widely used preconstrictor, yet its dose-response properties and kinetics of action on different vascular segments are not fully known. Here, we characterize the effects of U46619 on cortical arterioles and capillaries in <em>ex vivo</em> slices from rats and mice. Dose response curves tested in acute rat brain slices using 0 to 1000 nM U46619 showed that maximal constriction is reached at ∼300 nM in both arterioles and capillaries. Extended application of 200 nM U46619 (∼66 % maximal dose) over 2 h revealed that, on average, capillaries constrict faster than arterioles in rat brain slices. Cross-species examination in mouse tissue showed that vessels in mouse brain slices respond faster and constrict stronger on average than in rat brain slices, and that mouse capillaries also constrict faster than mouse arterioles. Our observations suggest that near-maximal preconstriction can be achieved in <em>ex vivo</em> experiments using 200–300 nM U46619, with a minimum incubation time of 20 min for studies involving capillaries and at least 30 min for studies involving arterioles.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104835"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556874","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}
Pub Date : 2025-09-01Epub Date: 2025-07-02DOI: 10.1016/j.mvr.2025.104839
Minyoung Kwak , Brian Benitez , Clara J. Mitchinson , Erik R. Snell , Haley C. Bergstrom
Purpose
This study investigated fatigability, reflected by torque responses and time to task failure (TTF), and time course of muscle oxygenation (SmO2) dynamics, as well as microvascular function assessed by near-infrared spectroscopy-vascular occlusion test (NIRS-VOT), in response to low-intensity, isometric forearm flexion anchored to a constant rating of perceived exertion (RPE) level of 3 (0–10 scale).
Methods
Twenty-five healthy young adults (22.9 ± 4.8 yr) completed a pre-exercise VOT, maximal voluntary isometric contraction (MVIC), and RPE-clamp exercise (RPE = 3), followed by post-exercise MVIC and VOT. Initial torque, TTF, and SmO2 dynamics were recorded during the RPE-clamp exercise. The time course of SmO2 was analyzed in 5 % TTF segments. During the VOTs, slope 1 (desaturation rate), minimum SmO2, slope 2 (reperfusion rate), maximum SmO2, and area under the curve (AUC) were recorded.
Results
MVIC torque significantly decreased from pre- to post-exercise (−13.9 % ± 14.0 %; p < 0.001). Initial torque was 23.3 ± 10.3 % MVIC, and TTF was 436.3 ± 252.0 s. SmO2 declined significantly from 0 % to 5 % TTF (p = 0.005), but returned to the initial value and remained stable across subsequent time intervals. Compared to pre-VOT, post-VOT exhibited significantly lower slope 1 (p < 0.001) and minimum SmO2 (p = 0.002), and greater maximum SmO2 (p = 0.013), while slope 2 (p = 0.065) and AUC (p = 0.379) were unchanged.
Conclusions
During the RPE-clamp exercise, the voluntary reduction in torque to maintain the assigned RPE likely resulted in stable muscle oxygen availability, preventing the development of hypoxic stimulus needed to enhance microvascular responsiveness. However, the low-intensity isometric RPE-clamp exercise combined with a post-VOT may enhance muscle aerobic metabolism through sustained oxygen utilization.
{"title":"Influence of isometric RPE-clamp exercise on fatigability, muscle oxygenation dynamics, and microvascular function in healthy young adults","authors":"Minyoung Kwak , Brian Benitez , Clara J. Mitchinson , Erik R. Snell , Haley C. Bergstrom","doi":"10.1016/j.mvr.2025.104839","DOIUrl":"10.1016/j.mvr.2025.104839","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigated fatigability, reflected by torque responses and time to task failure (TTF), and time course of muscle oxygenation (SmO<sub>2</sub>) dynamics, as well as microvascular function assessed by near-infrared spectroscopy-vascular occlusion test (NIRS-VOT), in response to low-intensity, isometric forearm flexion anchored to a constant rating of perceived exertion (RPE) level of 3 (0–10 scale).</div></div><div><h3>Methods</h3><div>Twenty-five healthy young adults (22.9 ± 4.8 yr) completed a pre-exercise VOT, maximal voluntary isometric contraction (MVIC), and RPE-clamp exercise (RPE = 3), followed by post-exercise MVIC and VOT. Initial torque, TTF, and SmO<sub>2</sub> dynamics were recorded during the RPE-clamp exercise. The time course of SmO<sub>2</sub> was analyzed in 5 % TTF segments. During the VOTs, slope 1 (desaturation rate), minimum SmO<sub>2</sub>, slope 2 (reperfusion rate), maximum SmO<sub>2</sub>, and area under the curve (AUC) were recorded.</div></div><div><h3>Results</h3><div>MVIC torque significantly decreased from pre- to post-exercise (−13.9 % ± 14.0 %; <em>p</em> < 0.001). Initial torque was 23.3 ± 10.3 % MVIC, and TTF was 436.3 ± 252.0 s. SmO<sub>2</sub> declined significantly from 0 % to 5 % TTF (<em>p</em> = 0.005), but returned to the initial value and remained stable across subsequent time intervals. Compared to pre-VOT, post-VOT exhibited significantly lower slope 1 (<em>p</em> < 0.001) and minimum SmO<sub>2</sub> (<em>p</em> = 0.002), and greater maximum SmO<sub>2</sub> (<em>p</em> = 0.013), while slope 2 (<em>p</em> = 0.065) and AUC (<em>p</em> = 0.379) were unchanged.</div></div><div><h3>Conclusions</h3><div>During the RPE-clamp exercise, the voluntary reduction in torque to maintain the assigned RPE likely resulted in stable muscle oxygen availability, preventing the development of hypoxic stimulus needed to enhance microvascular responsiveness. However, the low-intensity isometric RPE-clamp exercise combined with a post-VOT may enhance muscle aerobic metabolism through sustained oxygen utilization.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104839"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548508","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}
Pub Date : 2025-09-01Epub Date: 2025-06-25DOI: 10.1016/j.mvr.2025.104837
Hyerim Park , Steven L. Medarev , Joshua J. Maraj , Alexis Restrepo , Steven W. Copp , Judy M. Muller-Delp
Exercise training upregulates nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production in various tissues; however, little is known about the role of Nrf2 in exercise training-induced adaptations of blood vessels. This study investigated how deletion of Nrf2 affects vasomotor function in coronary resistance arteries in sedentary and exercise-trained rats. Wild-type (WT) and Nrf2 knockout (KO) rats underwent 10 weeks of treadmill exercise or remained sedentary. Coronary resistance arteries were isolated for assessment of vasomotor responses. In resistance arteries from Nrf2 KO rats, endothelin-induced constriction was blunted, but exercise training partially restored responsiveness to endothelin; after exercise training, responses to endothelin were not different between arteries from WT and Nrf2 KO rats. Similarly, KCl-induced constriction was reduced in arteries from Nrf2 KO rats, but exercise training reversed this loss of responsiveness to KCl. Nitric oxide (NO)-mediated vasodilation of coronary resistance arteries was not altered by deletion of Nrf2; however, exercise training enhanced NO-mediated dilation in arteries from WT, but not Nrf2 KO rats. Similarly, exercise training increased vasodilation to low concentrations of potassium (10 and 20 mM KCl) in arteries from WT, but not Nrf2 KO rats. These findings suggest that Nrf2 is critical to maintenance of contractile responses in coronary resistance arteries, but exercise training can restore contractile function through Nrf2-independent mechanisms. In contrast, vasodilatory responses to NO and low-level potassium are maintained in coronary resistance arteries from Nrf2-deficient rats, but exercise training fails to enhance these vasodilatory responses in the absence of Nrf2.
运动训练上调核因子红细胞2相关因子2 (Nrf2)的表达和各组织抗氧化剂的产生;然而,Nrf2在运动训练诱导的血管适应性中的作用知之甚少。本研究探讨了Nrf2缺失如何影响久坐和运动训练大鼠冠状动脉血管舒缩功能。野生型(WT)和Nrf2敲除(KO)大鼠进行10 周的跑步机运动或保持久坐。分离冠脉阻力动脉以评估血管舒缩反应。在Nrf2 KO大鼠的阻力动脉中,内皮素诱导的收缩被减弱,但运动训练部分恢复了对内皮素的反应性;运动训练后,WT和Nrf2 KO大鼠动脉对内皮素的反应没有差异。同样,Nrf2 KO大鼠的动脉中KCl诱导的收缩减少,但运动训练逆转了这种对KCl的反应性丧失。一氧化氮(NO)介导的冠状动脉血管舒张不因Nrf2的缺失而改变;然而,运动训练增强了WT大鼠no介导的动脉扩张,而Nrf2 KO大鼠则没有。同样,运动训练增加了WT大鼠动脉中低浓度钾(10和20 mM KCl)的血管舒张,但Nrf2 KO大鼠没有。这些发现表明Nrf2对于维持冠状动脉的收缩反应至关重要,但运动训练可以通过Nrf2独立的机制恢复收缩功能。相比之下,Nrf2缺乏的大鼠冠状动脉对NO和低水平钾的血管舒张反应得以维持,但在缺乏Nrf2的情况下,运动训练不能增强这些血管舒张反应。
{"title":"Nrf2 deficiency blunts exercise training-induced adaptations of coronary resistance arteries","authors":"Hyerim Park , Steven L. Medarev , Joshua J. Maraj , Alexis Restrepo , Steven W. Copp , Judy M. Muller-Delp","doi":"10.1016/j.mvr.2025.104837","DOIUrl":"10.1016/j.mvr.2025.104837","url":null,"abstract":"<div><div>Exercise training upregulates nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production in various tissues; however, little is known about the role of Nrf2 in exercise training-induced adaptations of blood vessels. This study investigated how deletion of Nrf2 affects vasomotor function in coronary resistance arteries in sedentary and exercise-trained rats. Wild-type (WT) and Nrf2 knockout (KO) rats underwent 10 weeks of treadmill exercise or remained sedentary. Coronary resistance arteries were isolated for assessment of vasomotor responses. In resistance arteries from Nrf2 KO rats, endothelin-induced constriction was blunted, but exercise training partially restored responsiveness to endothelin; after exercise training, responses to endothelin were not different between arteries from WT and Nrf2 KO rats. Similarly, KCl-induced constriction was reduced in arteries from Nrf2 KO rats, but exercise training reversed this loss of responsiveness to KCl. Nitric oxide (NO)-mediated vasodilation of coronary resistance arteries was not altered by deletion of Nrf2; however, exercise training enhanced NO-mediated dilation in arteries from WT, but not Nrf2 KO rats. Similarly, exercise training increased vasodilation to low concentrations of potassium (10 and 20 mM KCl) in arteries from WT, but not Nrf2 KO rats. These findings suggest that Nrf2 is critical to maintenance of contractile responses in coronary resistance arteries, but exercise training can restore contractile function through Nrf2-independent mechanisms. In contrast, vasodilatory responses to NO and low-level potassium are maintained in coronary resistance arteries from Nrf2-deficient rats, but exercise training fails to enhance these vasodilatory responses in the absence of Nrf2.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104837"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512168","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}
Pub Date : 2025-09-01Epub Date: 2025-06-14DOI: 10.1016/j.mvr.2025.104831
Sean M. Lubiak , Mason A. Howard , Jeffrey T. Schmidt , Nihar N. Patel , Anuj J. Prajapati , Niriham M. Shah , Emma K. Herring , David H. Fukuda , Jeffrey R. Stout , Joshua L. Keller , Ethan C. Hill
This investigation examined a moderate individualized pressure (i.e., percentage of total arterial occlusion pressure [TAOP]) compared to low and high absolute pressures on muscle tissue oxygenation (StO2) throughout ischemic preconditioning (IPC). Fifteen males randomly completed three cycles of IPC at a low (20 mmHg [IPCSHAM]), moderate (80% of TAOP [IPC80%]), and high (220 mmHg [IPC220mmHg]) pressure. Each cycle lasted 5 min at the assigned pressure, followed by 5 min of zero pressure on the dominant leg. StO2 was measured continuously and StO2 indices (i.e., downslope [StO2down], minimum [StO2min], upslope [StO2up], maximum [StO2max]) were analyzed with Bayesian models. StO2down and StO2min were pressure-dependent (IPCSHAM < IPC80% < IPC220mmHg) as indicated by zero absent from all 95% high-density intervals (95% HDI) and 100% probability of an effect (Prob = 100%). During IPC220mmHg, StO2up increased from cycle 1 to cycles 2 and 3 but plateaued from cycle 2 to 3 as indicated by zero absent from all 95% HDI's and Prob ≥87.6%. Additionally, StO2up was greater for IPC80% and IPC220mmHg relative to IPCSHAM for cycles 1 and 2 but was pressure-dependent during cycle 3 as indicated by zero absent from all 95% HDI's and Prob = 98.8%. Lastly, StO2max was greater for IPC220mmHg than IPCSHAM and IPC80% as indicated by zero absent from all 95% HDI's and Prob = 100%. Collectively, using moderate individualized pressure elicited similar StO2up as high absolute pressure, but only for cycles 1 and 2. These findings may be attributed to differences in the hypoxic-insult and/or vascular-related mechano-transduction stimuli.
{"title":"Time-course and pressure-dependent changes in microvascular responses during ischemic preconditioning","authors":"Sean M. Lubiak , Mason A. Howard , Jeffrey T. Schmidt , Nihar N. Patel , Anuj J. Prajapati , Niriham M. Shah , Emma K. Herring , David H. Fukuda , Jeffrey R. Stout , Joshua L. Keller , Ethan C. Hill","doi":"10.1016/j.mvr.2025.104831","DOIUrl":"10.1016/j.mvr.2025.104831","url":null,"abstract":"<div><div>This investigation examined a moderate individualized pressure (i.e., percentage of total arterial occlusion pressure [TAOP]) compared to low and high absolute pressures on muscle tissue oxygenation (StO<sub>2</sub>) throughout ischemic preconditioning (IPC). Fifteen males randomly completed three cycles of IPC at a low (20 mmHg [IPC<sub>SHAM</sub>]), moderate (80% of TAOP [IPC<sub>80%</sub>]), and high (220 mmHg [IPC<sub>220mmHg</sub>]) pressure. Each cycle lasted 5 min at the assigned pressure, followed by 5 min of zero pressure on the dominant leg. StO<sub>2</sub> was measured continuously and StO<sub>2</sub> indices (i.e., downslope [StO<sub>2down</sub>], minimum [StO<sub>2min</sub>], upslope [StO<sub>2up</sub>], maximum [StO<sub>2max</sub>]) were analyzed with Bayesian models. StO<sub>2down</sub> and StO<sub>2min</sub> were pressure-dependent (IPC<sub>SHAM</sub> < IPC<sub>80%</sub> < IPC<sub>220mmHg</sub>) as indicated by zero absent from all 95% high-density intervals (95% HDI) and 100% probability of an effect (Prob = 100%). During IPC<sub>220mmHg</sub>, StO<sub>2up</sub> increased from cycle 1 to cycles 2 and 3 but plateaued from cycle 2 to 3 as indicated by zero absent from all 95% HDI's and Prob ≥87.6%. Additionally, StO<sub>2up</sub> was greater for IPC<sub>80%</sub> and IPC<sub>220mmHg</sub> relative to IPC<sub>SHAM</sub> for cycles 1 and 2 but was pressure-dependent during cycle 3 as indicated by zero absent from all 95% HDI's and Prob = 98.8%. Lastly, StO<sub>2max</sub> was greater for IPC<sub>220mmHg</sub> than IPC<sub>SHAM</sub> and IPC<sub>80%</sub> as indicated by zero absent from all 95% HDI's and Prob = 100%. Collectively, using moderate individualized pressure elicited similar StO<sub>2up</sub> as high absolute pressure, but only for cycles 1 and 2. These findings may be attributed to differences in the hypoxic-insult and/or vascular-related mechano-transduction stimuli.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104831"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310193","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}
Pub Date : 2025-09-01Epub Date: 2025-06-20DOI: 10.1016/j.mvr.2025.104832
Zhaoxia Zheng , Lei Hu , Yue Zhang , Nianen Liu , Xiaoya Gu , Shuang Song , Xiaobing Yu
Purpose
To investigate choroidal changes in different stages of diabetic retinopathy (DR), and determine the effect of panretinal photocoagulation (PRP) on choroid based on volumetric measurements of ultrawide-field swept-source optical coherence tomography angiography (UWF-SS-OCTA).
Methods
This observational study included 56 healthy controls, 192 treatment-naïve DR patients, and 42 PRP-treated DR patients who have undergone UWF-SS-OCTA measurements. Treatment-naïve DR patients were further grouped according to varying severity of DR. Choroidal parameters were analyzed and compared among these groups according to central and peripheral areas. Spearman analysis was performed to determine the association between non-perfusion area (NPA) and choroidal parameters.
Results
Compared with healthy controls, choroidal thickness (CT) and volume (CV), including both vascular and stromal volume (CVV/a and CSV/a) were decreased in treatment-naïve DR patients in full range, while choroidal vascularity index (CVI) decreased only in the peripheral area (P = 0.04). In detail, choroid was thinning in no-DR (NDR) and mild NPDR, followed by an increased trend in moderate and late stages of DR. NPA was positively associated with CT, CV, CVV/a, and CSV/a in moderate and late stages of DR. Choroidal parameters decreased in PRP-treated eyes except for an increase of CVI in the central area.
Conclusion
Choroid was thinning in treatment-naïve DR eyes. Specifically, choroid decreased in the early stage and further increased with DR progression; increased expression of VEGF may be a key factor in choroidal thickening. PRP treatment could contribute to the redistribution of choroidal blood flow and improve the perfusion of the macula.
{"title":"Three-dimensional choroidal changes in diabetes and diabetic retinopathy: An ultrawide-field swept-source optical coherence tomography angiography study","authors":"Zhaoxia Zheng , Lei Hu , Yue Zhang , Nianen Liu , Xiaoya Gu , Shuang Song , Xiaobing Yu","doi":"10.1016/j.mvr.2025.104832","DOIUrl":"10.1016/j.mvr.2025.104832","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate choroidal changes in different stages of diabetic retinopathy (DR), and determine the effect of panretinal photocoagulation (PRP) on choroid based on volumetric measurements of ultrawide-field swept-source optical coherence tomography angiography (UWF-SS-OCTA).</div></div><div><h3>Methods</h3><div>This observational study included 56 healthy controls, 192 treatment-naïve DR patients, and 42 PRP-treated DR patients who have undergone UWF-SS-OCTA measurements. Treatment-naïve DR patients were further grouped according to varying severity of DR. Choroidal parameters were analyzed and compared among these groups according to central and peripheral areas. Spearman analysis was performed to determine the association between non-perfusion area (NPA) and choroidal parameters.</div></div><div><h3>Results</h3><div>Compared with healthy controls, choroidal thickness (CT) and volume (CV), including both vascular and stromal volume (CVV/a and CSV/a) were decreased in treatment-naïve DR patients in full range, while choroidal vascularity index (CVI) decreased only in the peripheral area (<em>P</em> = 0.04). In detail, choroid was thinning in no-DR (NDR) and mild NPDR, followed by an increased trend in moderate and late stages of DR. NPA was positively associated with CT, CV, CVV/a, and CSV/a in moderate and late stages of DR. Choroidal parameters decreased in PRP-treated eyes except for an increase of CVI in the central area.</div></div><div><h3>Conclusion</h3><div>Choroid was thinning in treatment-naïve DR eyes. Specifically, choroid decreased in the early stage and further increased with DR progression; increased expression of VEGF may be a key factor in choroidal thickening. PRP treatment could contribute to the redistribution of choroidal blood flow and improve the perfusion of the macula.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104832"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330829","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}
Pub Date : 2025-09-01Epub Date: 2025-07-19DOI: 10.1016/j.mvr.2025.104845
Veronika Frelichova , Robert Bem , Jaroslav Chlupac , Michal Dubsky , Jitka Husakova , Andrea Nemcova , Ludek Voska , Zuzana Simunkova , Filip Tichanek , Jiri Fronek
There is a lack of reliable in vivo models that replicate limb-threatening ischemia in humans. To fill this gap, we developed and validated two novel porcine ischemic models: ischemic limb and dorsal flap models, both with and without streptozotocin-induced hyperglycemia (N = 3 per group, 12 in total). Hind limb ischemia model was induced via different arterial ligations, with two ischemic and three control wounds per animal. In the flap model, four full-thickness flaps were created on the dorsum with silicone sheets to block reperfusion, and excisional wounds were made on the top. One non-ischemic wound served as control. Transcutaneous oxygen pressure (TcPO2), wound area, and microvascular density were measured, with TcPO2 and wound area assessed longitudinally. Data analysis focused on detailed visualization and Bayesian hierarchical modelling to account for the small sample size. Developed models exhibited stable ischemia and prolonged wound healing, with TcPO2 remaining under 30 mmHg over 28 days, and wound healing extending beyond two weeks. The flap model showed slower TcPO2 recovery and greater chronicity compared to the limb model, without reliable effect of hyperglycemia. Thus, the porcine flap model shows the highest potential as a relevant model for chronic limb-threatening ischemia.
{"title":"Novel in vivo porcine models of chronic ischemic tissue","authors":"Veronika Frelichova , Robert Bem , Jaroslav Chlupac , Michal Dubsky , Jitka Husakova , Andrea Nemcova , Ludek Voska , Zuzana Simunkova , Filip Tichanek , Jiri Fronek","doi":"10.1016/j.mvr.2025.104845","DOIUrl":"10.1016/j.mvr.2025.104845","url":null,"abstract":"<div><div>There is a lack of reliable in vivo models that replicate limb-threatening ischemia in humans. To fill this gap, we developed and validated two novel porcine ischemic models: ischemic limb and dorsal flap models, both with and without streptozotocin-induced hyperglycemia (<em>N</em> = 3 per group, 12 in total). Hind limb ischemia model was induced via different arterial ligations, with two ischemic and three control wounds per animal. In the flap model, four full-thickness flaps were created on the dorsum with silicone sheets to block reperfusion, and excisional wounds were made on the top. One non-ischemic wound served as control. Transcutaneous oxygen pressure (TcPO<sub>2</sub>), wound area, and microvascular density were measured, with TcPO<sub>2</sub> and wound area assessed longitudinally. Data analysis focused on detailed visualization and Bayesian hierarchical modelling to account for the small sample size. Developed models exhibited stable ischemia and prolonged wound healing, with TcPO<sub>2</sub> remaining under 30 mmHg over 28 days, and wound healing extending beyond two weeks. The flap model showed slower TcPO<sub>2</sub> recovery and greater chronicity compared to the limb model, without reliable effect of hyperglycemia. Thus, the porcine flap model shows the highest potential as a relevant model for chronic limb-threatening ischemia.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104845"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682787","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}
Pub Date : 2025-09-01Epub Date: 2025-07-16DOI: 10.1016/j.mvr.2025.104844
Reza Talaie, Pooya Torkian, Anthony Spano, Alexander Clayton, Jafar Golzarian
Purpose
The study aimed to examine neovascularization in murine osteoarthritis (OA) using micro-computed tomography (μCT).
Materials and methods
OA was induced in eighteen mice through intra-articular collagenase injection, designating the left hindlimbs as OA models and the right hindlimbs as controls. Mice were monitored for 4, 8, or 12 weeks post-induction. Hindlimbs underwent overnight tissue fixation and were then subjected to μCT scanning. Quantification of unnamed arterial branches spanned from the femoral artery's terminal branching point to 2.5 mm below the tibial plateau.
Results
Baseline characteristics did not differ significantly between control and OA-induced groups (p > 0.05). Collagenase-treated limbs showed a significantly higher number of unnamed arterial branches compared to controls (11.6 vs. 7.5, p < 0.001), reflecting increased neovascularization. This elevation persisted across all post-induction time points, with no significant time-dependent trend (p = 0.09) or interaction between time and treatment group (p = 0.17). Spatial analysis revealed that neovessels were predominantly localized to peri-meniscal (61 %) and subchondral (29 %) regions.
Conclusion
Collagenase-induced OA in mice results in sustained and spatially patterned neovascularization, detectable using non-contrast μCT. These findings underscore the utility of μCT for tracking vascular remodeling in OA and highlight potential anatomical targets for angiogenesis-modulating therapies.
{"title":"Evaluation of neovascularization in murine osteoarthritis using micro-computed tomography","authors":"Reza Talaie, Pooya Torkian, Anthony Spano, Alexander Clayton, Jafar Golzarian","doi":"10.1016/j.mvr.2025.104844","DOIUrl":"10.1016/j.mvr.2025.104844","url":null,"abstract":"<div><h3>Purpose</h3><div>The study aimed to examine neovascularization in murine osteoarthritis (OA) using micro-computed tomography (μCT).</div></div><div><h3>Materials and methods</h3><div>OA was induced in eighteen mice through intra-articular collagenase injection, designating the left hindlimbs as OA models and the right hindlimbs as controls. Mice were monitored for 4, 8, or 12 weeks post-induction. Hindlimbs underwent overnight tissue fixation and were then subjected to μCT scanning. Quantification of unnamed arterial branches spanned from the femoral artery's terminal branching point to 2.5 mm below the tibial plateau.</div></div><div><h3>Results</h3><div>Baseline characteristics did not differ significantly between control and OA-induced groups (p > 0.05). Collagenase-treated limbs showed a significantly higher number of unnamed arterial branches compared to controls (11.6 vs. 7.5, p < 0.001), reflecting increased neovascularization. This elevation persisted across all post-induction time points, with no significant time-dependent trend (p = 0.09) or interaction between time and treatment group (p = 0.17). Spatial analysis revealed that neovessels were predominantly localized to peri-meniscal (61 %) and subchondral (29 %) regions.</div></div><div><h3>Conclusion</h3><div>Collagenase-induced OA in mice results in sustained and spatially patterned neovascularization, detectable using non-contrast μCT. These findings underscore the utility of μCT for tracking vascular remodeling in OA and highlight potential anatomical targets for angiogenesis-modulating therapies.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104844"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667978","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}
Pub Date : 2025-07-01Epub Date: 2025-05-18DOI: 10.1016/j.mvr.2025.104820
Changsheng Chen , Xi Xu , Jiahao Lu , Yuqing Xiang , Linsheng Shi , Dong Liu
The blood-brain barrier (BBB) serves as a highly selective interface that regulates the transport of molecules between the blood and the brain. Its integrity is essential for maintaining neuronal homeostasis and preventing neuroinflammation. Hyperglycemia, a hallmark of diabetes, is linked to cognitive deficits and central nervous system (CNS) pathologies, including vascular dementia, stroke, and Alzheimer's disease, with BBB damage as a potential contributing factor. As the global prevalence of diabetes rises, understanding the connection between hyperglycemia and BBB dysfunction may facilitate the development of novel treatments that protect or restore BBB integrity, thereby alleviating the neurological complications of diabetes. Furthermore, it may aid in the development of targeted therapies for diabetes-related neurological complications. This literature review examines the emerging insights into the relationship between hyperglycemia and BBB dysfunction. It focuses on the mechanisms underlying BBB dysfunction, the clinical manifestations of this dysfunction in diabetes and cerebrovascular diseases, and potential therapeutic interventions.
{"title":"Hyperglycemia-induced blood-brain barrier dysfunction: Mechanisms and therapeutic interventions","authors":"Changsheng Chen , Xi Xu , Jiahao Lu , Yuqing Xiang , Linsheng Shi , Dong Liu","doi":"10.1016/j.mvr.2025.104820","DOIUrl":"10.1016/j.mvr.2025.104820","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) serves as a highly selective interface that regulates the transport of molecules between the blood and the brain. Its integrity is essential for maintaining neuronal homeostasis and preventing neuroinflammation. Hyperglycemia, a hallmark of diabetes, is linked to cognitive deficits and central nervous system (CNS) pathologies, including vascular dementia, stroke, and Alzheimer's disease, with BBB damage as a potential contributing factor. As the global prevalence of diabetes rises, understanding the connection between hyperglycemia and BBB dysfunction may facilitate the development of novel treatments that protect or restore BBB integrity, thereby alleviating the neurological complications of diabetes. Furthermore, it may aid in the development of targeted therapies for diabetes-related neurological complications. This literature review examines the emerging insights into the relationship between hyperglycemia and BBB dysfunction. It focuses on the mechanisms underlying BBB dysfunction, the clinical manifestations of this dysfunction in diabetes and cerebrovascular diseases, and potential therapeutic interventions.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104820"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088816","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}
Pub Date : 2025-07-01Epub Date: 2025-05-07DOI: 10.1016/j.mvr.2025.104817
Jinhui Zhou , Chao Ni , Zhenquan Wang , Yuhan Xia , Hongying Shi , Xiaoshan Zhao , Yufei Chen , Chenchen Liu , Xing Rong , Rongzhou Wu , Maoping Chu , Huixian Qiu
Objective
Kawasaki disease (KD) is an acute systemic inflammation, that affects medium-sized arteries. Coronary artery lesions (CALs) were the most serious complication or sequelae of KD. The intense inflammatory response leads to platelet activation, further exacerbating inflammation, which plays an important role in the pathogenesis of CALs in KD patients. Plus, coagulation factors are closely related to platelet activation. Therefore, we speculate that the activated partial thromboplastin time (APTT), an indicator of coagulation factor function, may be involved in the occurrence of CALs, but it has not been explored yet. This study aims to investigate the effect of the APTT level on CALs occurrence in the acute phase of KD.
Methods
A total of 2303 KD patients during a 10-year period were recruited at the Wenzhou Medical University affiliated Yuying Children's Hospital. A total of 1715 patients who completed the follow-up were enrolled in the final analysis and were divided into the low APTT group and the high APTT group at a 46 s cutoff before receiving intravenous immunoglobulin (IVIG) treatment. Multiple logistic regression analysis and stratified analysis were utilized to evaluate the independent impact of APTT levels on the occurrence of CALs and to determine the impact of APTT levels on the occurrence of CALs in different subgroups, respectively.
Results
The incidence of CALs in the low APTT group and the high APTT group was 12.5 % and 17.5 %, respectively (P = 0.005). Patients with high APTT levels had higher CRP levels (P < 0.001). High APTT levels were the independent risk factor on the occurrence of CALs; the adjusted odds ratio (OR) was 1.523 (95 % CI: 1.144, 2.028). Similar results were found in stratification analysis and sensitivity analysis.
Conclusions
KD patients with high APTT levels (≥46 s) before IVIG treatment may be more prone to developing CALs in the acute phase of KD.
{"title":"Activated partial thromboplastin time levels and coronary artery lesions in Kawasaki disease: A retrospective cohort study","authors":"Jinhui Zhou , Chao Ni , Zhenquan Wang , Yuhan Xia , Hongying Shi , Xiaoshan Zhao , Yufei Chen , Chenchen Liu , Xing Rong , Rongzhou Wu , Maoping Chu , Huixian Qiu","doi":"10.1016/j.mvr.2025.104817","DOIUrl":"10.1016/j.mvr.2025.104817","url":null,"abstract":"<div><h3>Objective</h3><div>Kawasaki disease (KD) is an acute systemic inflammation, that affects medium-sized arteries. Coronary artery lesions (CALs) were the most serious complication or sequelae of KD. The intense inflammatory response leads to platelet activation, further exacerbating inflammation, which plays an important role in the pathogenesis of CALs in KD patients. Plus, coagulation factors are closely related to platelet activation. Therefore, we speculate that the activated partial thromboplastin time (APTT), an indicator of coagulation factor function, may be involved in the occurrence of CALs, but it has not been explored yet. This study aims to investigate the effect of the APTT level on CALs occurrence in the acute phase of KD.</div></div><div><h3>Methods</h3><div>A total of 2303 KD patients during a 10-year period were recruited at the Wenzhou Medical University affiliated Yuying Children's Hospital. A total of 1715 patients who completed the follow-up were enrolled in the final analysis and were divided into the low APTT group and the high APTT group at a 46 s cutoff before receiving intravenous immunoglobulin (IVIG) treatment. Multiple logistic regression analysis and stratified analysis were utilized to evaluate the independent impact of APTT levels on the occurrence of CALs and to determine the impact of APTT levels on the occurrence of CALs in different subgroups, respectively.</div></div><div><h3>Results</h3><div>The incidence of CALs in the low APTT group and the high APTT group was 12.5 % and 17.5 %, respectively (<em>P</em> = 0.005). Patients with high APTT levels had higher CRP levels (<em>P</em> < 0.001). High APTT levels were the independent risk factor on the occurrence of CALs; the adjusted odds ratio (OR) was 1.523 (95 % CI: 1.144, 2.028). Similar results were found in stratification analysis and sensitivity analysis.</div></div><div><h3>Conclusions</h3><div>KD patients with high APTT levels (≥46 s) before IVIG treatment may be more prone to developing CALs in the acute phase of KD.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104817"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937928","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}