Microcirculation最新文献

Models of Hydration Dependent Lymphatic Opening, Interstitial Fluid Flows and Ambipolar Diffusion. 取决于水合作用的淋巴管开放、间质流和常压扩散模型。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-11-21 DOI: 10.1111/micc.12894

Alf H Øien, Olav Tenstad, Helge Wiig

Objective: A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking.

Methods: Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix.

Results: We first model a lymphatic opening mechanism at relevant hydrations of the interstitium. At each hydration affecting tissue strain, two equations coupled in time are developed and solved with the new lymphatic opening and particle draining mechanism. The lymphatic opening mechanism is then included in a new model of interstitial fluid and macromolecular flow where the influence of different exclusion and available volumes for charged and neutral particles are quantified. For therapeutic interactions with cells, essential differences are found between electrically charged and neutral therapeutic substances. The interstitial fluid hydrostatic pressure gradient and flow are expressed through an extended Darcy equation, derived using similar methods as in kinetic theory of dense gases and fluid flows. Finally, a model for ambipolar diffusion of electrically charged macromolecules in tissue is developed.

Conclusions: Our study will inform transport of charged and neutral macromolecules between the vasculature, interstitium, and the lymphatic system, thus having implications for tissue uptake of therapeutic agents.

目的：目前还缺乏通过数学/物理建模对组织中液体交换和初始淋巴形成作用的理论认识：缺乏通过数学/物理建模对组织中液体交换和初始淋巴形成的作用的理论理解。方法：在此，我们提出了三种组织模型，这些组织因糖胺聚糖与细胞外基质相互作用而富含固定负电荷：我们首先模拟了间质相关水合作用下的淋巴开放机制。在每个影响组织应变的水合作用下，我们建立了两个时间耦合方程，并利用新的淋巴开放和微粒排出机制进行求解。然后将淋巴开放机制纳入间质流体和大分子流动的新模型中，对带电粒子和中性粒子的不同排斥和可用体积的影响进行量化。在治疗药物与细胞的相互作用方面，带电和中性治疗药物之间存在本质区别。间质流体的静水压力梯度和流动是通过扩展达西方程来表示的，其推导方法与稠密气体和流体流动的动力学理论类似。最后，建立了带电大分子在组织中的极性扩散模型：我们的研究将为带电和中性大分子在血管、间质和淋巴系统之间的传输提供信息，从而对治疗药物的组织吸收产生影响。

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引用次数: 0

Pressure-Induced Microvascular Reactivity With Whole Foot Loading Is Unique Across the Human Foot Sole. 全足加载时压力引起的微血管反应是人类足底独有的。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-11-12 DOI: 10.1111/micc.12893

Erika E Howe, Leah R Bent

Background: Foot sole plantar pressure generates transient but habitual cutaneous ischemia, which is even more exacerbated in atypical gait patterns. Thus, adequate post-occlusive reactive hyperaemia (PORH) is necessary to maintain skin health. Plantar pressure regional variance during daily tasks potentially generates region-specific PORH, crucial for ischemic defence.

Aims: The current work investigated regional PORH across the human foot sole resulting from stance-like loading.

Materials & methods: A loading device equipped with an in-line laser speckle contrast imager measured blood flux before, during, and after whole-foot loading for 2 and 10 min durations at 15% and 50% body weight. Flux was compared between six regions: the heel, lateral arch, medial arch, and fifth, third, and first metatarsals (MT).

Results: Baseline flux was significantly greater in the 1MT and 3MT than all other regions. Loading occluded the heel, 5MT and 3MT more than all other regions. Regional PORH peak, time to peak, area under the curve, and recovery rate were ranked between regions.

Discussion: The 3MT, followed by 5MT, overall had the strongest PORH response, suggesting a heightened protection against ischemia compared to other regions.

Conclusion: This work highlights regional variations within a healthy foot, providing a framework for future ulcer risk assessments and interventions to preserve foot health.

背景：足底足底压力会产生短暂但习惯性的皮肤缺血，这种缺血在非典型步态下会更加严重。因此，充分的闭塞后反应性高血症（PORH）是维持皮肤健康的必要条件。在日常工作中，足底压力的区域差异可能会产生特定区域的 PORH，这对于缺血防御至关重要：装有在线激光斑点对比成像仪的负重装置在体重为 15%和 50%、持续 2 分钟和 10 分钟的全足负重之前、期间和之后测量血流量。对六个区域的血流量进行了比较：足跟、足弓外侧、足弓内侧、第五、第三和第一跖骨（MT）：结果：第一跖骨和第三跖骨的基线通量明显高于所有其他区域。加载对脚跟、第五跖骨和第三跖骨的闭塞程度高于所有其他区域。各区域的 PORH 峰值、达到峰值的时间、曲线下面积和恢复率在各区域之间进行了排名：讨论：总体而言，3MT 的 PORH 反应最强，其次是 5MT，这表明与其他区域相比，3MT 对缺血的保护作用更强：这项研究强调了健康足部的区域差异，为未来的溃疡风险评估和保护足部健康的干预措施提供了框架。

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引用次数: 0

Microcirculatory Perfusion Disturbances During Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review. 静脉-动脉体外膜氧合过程中的微循环灌注紊乱：系统回顾。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-11-01 Epub Date: 2024-10-10 DOI: 10.1111/micc.12891

Carolien Volleman, S Jorinde Raasveld, Faridi S Jamaludin, Alexander P J Vlaar, Charissa E van den Brom

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in case of potentially reversible cardiac failure and restores systemic hemodynamics. However, whether this is followed by improvement of microcirculatory perfusion is unknown. Moreover, critically ill patients have possible pre-existing microcirculatory perfusion disturbances. Therefore, this review provides an overview of alterations in sublingual microcirculatory perfusion in critically ill adult patients receiving VA-ECMO support. Pubmed, Embase (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched according to PRISMA guidelines. Studies reporting sublingual microcirculatory perfusion measurements in adult patients supported by VA-ECMO were included. Outcome parameters included small vessel density (SVD), perfused vessel density (PVD), perfused small vessel density (PSVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and the heterogeneity index (HI). The protocol was registered at PROSPERO (CRD42021243930). The search identified 1215 studies of which 11 were included. Cardiogenic shock was the most common indication for VA-ECMO (n=8). Three studies report increased PSVD, PPV, and MFI 24 hours after initiation of ECMO compared to pre-ECMO. Nonetheless, microcirculatory perfusion stabilized thereafter. Four out of four studies showed higher PSVD and PPV in survivors compared to non-survivors. Over time, survivors showed recovery of microcirculatory perfusion within hours of initiation of ECMO, whereas this was absent in non-survivors. Notwithstanding the limited sample, VA-ECMO seems to improve microcirculatory perfusion shortly after initiation of ECMO, especially in survivors. Further research in larger cohorts is needed to clarify the longitudinal effects of ECMO on microcirculatory perfusion.

静脉-动脉体外膜肺氧合（VA-ECMO）用于潜在可逆性心力衰竭，可恢复全身血液动力学。然而，微循环灌注是否会随之改善尚不清楚。此外，重症患者可能已经存在微循环灌注障碍。因此，本综述概述了接受 VA-ECMO 支持的重症成人患者舌下微循环灌注的改变。根据 PRISMA 指南对 Pubmed、Embase (Ovid)、Cochrane Central Register of Controlled Trials 和 Web of Science 进行了系统检索。结果参数包括小血管密度（special vessel density）、血管密度（special vessel density）、血管密度（special vessel density）、血管密度（special vessel density）和血管密度（special vessel density）。结果参数包括小血管密度（SVD）、灌注血管密度（PVD）、灌注小血管密度（PSVD）、灌注血管比例（PPV）、微血管流量指数（MFI）和异质性指数（HI）。研究方案已在 PROSPERO（CRD42021243930）上注册。搜索发现了 1215 项研究，其中 11 项被纳入。心源性休克是 VA-ECMO 最常见的适应症（8 项）。三项研究报告称，与 ECMO 前相比，ECMO 启动 24 小时后 PSVD、PPV 和 MFI 均有所增加。尽管如此，微循环灌注随后趋于稳定。四项研究中有四项显示，与非幸存者相比，幸存者的 PSVD 和 PPV 较高。随着时间的推移，幸存者在启动 ECMO 后数小时内微循环灌注恢复，而非幸存者则没有这种情况。尽管样本有限，但 VA-ECMO 似乎在启动 ECMO 后不久就能改善微循环灌注，尤其是在幸存者中。需要在更大的队列中开展进一步研究，以明确 ECMO 对微循环灌注的纵向影响。

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引用次数: 0

Effects of Beraprost on Intestinal Microcirculation and Barrier Function in a Mouse Model of Renal Failure 贝前列素对肾衰竭小鼠模型肠道微循环和屏障功能的影响

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-30 DOI: 10.1111/micc.12889

Akira Hirano, Hiroyuki Kadoya, Masanobu Takasu, Tsukasa Iwakura, Eriko Kajimoto, Rie Tatsugawa, Takumi Matsuura, Hajimu Kurumatani, Toshiya Yamamoto, Kengo Kidokoro, Seiji Kishi, Hajime Nagasu, Tamaki Sasaki, Naoki Kashihara

Objective

Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI₂), an endothelial cell-produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood. We hypothesized that PGI₂ improves intestinal microcirculation and barrier function via endothelial protective effects.

Methods

ICR and ICGN (a spontaneous nephrotic model) mice were used in this study. Intestinal microcirculation was visualized in vivo to investigate PGI₂ effects. Beraprost served as PGI₂. PGI₂ administration spanned 4 weeks, following which we assessed its influence on intestinal endothelial, intestinal barrier, and renal functions.

Results

We visualized intestinal microcirculation and endothelial glycocalyx in the intestinal blood vessels. Beraprost administration induced a 1.2-fold dilatation of the vascular diameter of the small intestine. Intestinal blood flow in ICGN mice was significantly reduced compared that in ICR mice but improved with beraprost administration. ICGN mice exhibited reduced serum albumin levels, decreased ambulation, an imbalance in intestinal reactive oxygen species (ROS)/nitric oxide (NO), and impaired tight junctions; all were ameliorated by beraprost administration.

Conclusions

Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure.

目的：内皮功能障碍在慢性肾脏病的发病机制中起着重要作用。前列环素（PGI2）是内皮细胞产生的一种内源性前列腺素，在维持内皮功能方面起着至关重要的作用。然而，它对肠道微循环和屏障功能的影响尚不完全清楚。我们假设 PGI2 可通过内皮保护作用改善肠道微循环和屏障功能：方法：本研究使用了 ICR 和 ICGN（一种自发性肾病模型）小鼠。方法：本研究使用 ICR 和 ICGN（自发性肾病模型）小鼠，在体内观察肠道微循环以研究 PGI2 的作用。贝前列素用作 PGI2。PGI2 给药持续 4 周，随后我们评估了它对肠道内皮、肠道屏障和肾功能的影响：结果：我们观察了肠道微循环和肠道血管内皮糖萼。服用贝前列素可使小肠血管直径扩张1.2倍。ICGN 小鼠的肠道血流量与 ICR 小鼠相比明显减少，但服用贝前列素后有所改善。ICGN 小鼠表现出血清白蛋白水平降低、活动能力下降、肠道活性氧（ROS）/一氧化氮（NO）失衡以及紧密连接受损；服用贝前列素后，这些症状都得到了改善：结论：贝前列素能通过改善活性氧/一氧化氮失衡改善肠道微循环和屏障功能，从而减少肾衰竭期间的体力活动。

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引用次数: 0

Cerebral Microcirculation: Progress and Outlook of Laser Doppler Flowmetry in Neurosurgery and Neurointensive Care 脑微循环：激光多普勒血流测量在神经外科和神经重症监护中的应用进展与展望》。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-28 DOI: 10.1111/micc.12884

Karin Wårdell, Johan Richter, Peter Zsigmond

Laser Doppler flowmetry (LDF) is a well-established technique for the investigation of tissue microcirculation. Compared to skin, the use in the human brain is sparse. The measurement of cerebral microcirculation in neurointensive care and during neurosurgery is challenging and requires adaptation to the respective clinical setting. The aim of the review is to present state of the art and progress in neurosurgery and neurointensive care where LDF has proven useful and can find clinical importance in the investigation of cerebral microcirculation. The literature in the field is summarized and recent technical improvements regarding LDF systems and fiber optical probe designs for neurosurgical and neurocritical care described. By combining two signals from the LDF unit, the measurement of the microcirculation (Perfusion) and gray whiteness (TLI) of the brain tissue, the full potential of the device is achieved. For example, a forward-looking LDF-probe detects high-risk hemorrhage areas and gray-white matter boundaries along intraoperative trajectories during stereotactic neurosurgery. Proof of principles are given for LDF as a guidance tool in deep brain stimulation implantation, brain tumor needle biopsies, and as long-term monitoring device in neurocritical care. With well-designed fiber optical probes, surgical fixation, and signal processing for movement reduction, LDF monitoring of the cerebral microcirculation is successful up to 10 days. The use of LDF can be combined with other physiological measurement techniques, for example, fluorescence spectroscopy for identification of glioblastoma during tumor surgery. Fiber optics can also be used during magnetic resonance imaging (MRI). Despite the many advantages, fiber optical LDF has not yet reached its full potential in clinical neuro-applications. Multicenter studies are required to further evaluate LDF in neurosurgery and neurointensive care. In conclusion, the present status of LDF in neurosurgery and neurointensive care has been reviewed. By combining Perfusion and TLI with tailored probe designs the full potential of LDF can be achived in measuring cerebral microcirculation. This includes guidance during DBS implantation and needle biopsies, and long-term monitoring in neurocritical care.

激光多普勒血流测量仪（LDF）是一种用于研究组织微循环的成熟技术。与皮肤相比，该技术在人脑中的应用还很少。在神经重症监护和神经外科手术中测量脑微循环具有挑战性，需要适应相应的临床环境。本综述旨在介绍 LDF 在神经外科和神经重症监护中的应用现状和进展，LDF 已被证明在脑微循环研究中非常有用并具有重要的临床意义。文章概述了该领域的文献，并介绍了用于神经外科和神经重症监护的 LDF 系统和光纤探头设计的最新技术改进。通过结合 LDF 设备的两个信号，即脑组织微循环（灌注）和灰白色度（TLI）的测量，可以充分发挥设备的潜力。例如，在立体定向神经外科手术过程中，前视 LDF 探针可沿术中轨迹检测高风险出血区域和灰白质边界。LDF 作为脑深部刺激植入、脑肿瘤针刺活检的引导工具，以及作为神经重症监护的长期监测设备，其原理已得到验证。通过精心设计的光纤探头、手术固定和减少移动的信号处理，LDF 可成功监测大脑微循环长达 10 天。LDF 的使用可与其他生理测量技术相结合，例如在肿瘤手术过程中使用荧光光谱来识别胶质母细胞瘤。光纤还可用于磁共振成像（MRI）。尽管光纤 LDF 具有诸多优势，但其在临床神经应用中的潜力尚未得到充分发挥。需要进行多中心研究，进一步评估 LDF 在神经外科和神经重症监护中的应用。总之，本文回顾了 LDF 在神经外科和神经重症监护中的应用现状。通过将灌注和 TLI 与量身定制的探头设计相结合，LDF 可以在测量脑微循环方面充分发挥潜力。这包括在 DBS 植入和针刺活检过程中提供指导，以及在神经重症监护中进行长期监测。

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引用次数: 0

Overview of Lymphatic Muscle Cells in Development, Physiology, and Disease 发育、生理和疾病中的淋巴肌肉细胞概述。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-27 DOI: 10.1111/micc.12887

Guillermo Arroyo-Ataz, Dennis Jones

Lymphatic muscle cells (LMCs) are indispensable for proper functioning of the lymphatic system, as they provide the driving force for lymph transport. Recent studies have advanced our understanding of the molecular mechanisms that regulate LMCs, which control rhythmic contraction and vessel tone of lymphatic vessels—traits also found in cardiac and vascular smooth muscle. In this review, we discuss the molecular pathways that orchestrate LMC-mediated contractility and summarize current knowledge about their developmental origin, which may shed light on the distinct contractile characteristics of LMCs. Further, we highlight the growing evidence implicating LMC dysregulation in the pathogenesis of lymphedema and other diseases related to lymphatic vessel dysfunction. Given the limited number and efficacy of existing therapies to treat lymphedema, LMCs present a promising focus for identifying novel therapeutic targets aimed at improving lymphatic vessel contractility. Here, we discuss LMCs in health and disease, as well as therapeutic strategies aimed at targeting them to improve lymphatic vessel function.

淋巴肌细胞（LMC）是淋巴系统正常运作不可或缺的因素，因为它们为淋巴运输提供动力。淋巴肌细胞控制淋巴管的节律性收缩和血管张力--这也是心肌和血管平滑肌的特性。最近的研究加深了我们对调节淋巴肌细胞的分子机制的了解。在这篇综述中，我们讨论了协调 LMC 介导的收缩性的分子途径，并总结了目前有关其发育起源的知识，这些知识可能揭示了 LMC 独特的收缩特性。此外，我们还强调了越来越多的证据表明，LMC 失调与淋巴水肿和其他淋巴管功能障碍相关疾病的发病机制有关。鉴于治疗淋巴水肿的现有疗法在数量和疗效上都很有限，LMCs 为确定旨在改善淋巴管收缩性的新型治疗靶点提供了一个有希望的焦点。在此，我们将讨论健康和疾病中的淋巴管，以及针对淋巴管改善淋巴管功能的治疗策略。

引用次数: 0

Quantification of Video Sequences of the Microcirculation: A Comparison Between Automated Analysis Using Analysis Manager and Manual Analysis Using Capillary Mapper 微循环视频序列量化：使用分析管理器进行自动分析与使用毛细管映射器进行手动分析的比较。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-26 DOI: 10.1111/micc.12890

Fabian Müller-Graf, Dominik Wrede, Lena Bork, Gerd Klinkmann, Moritz Flick, Daniel A. Reuter, Amelie R. Zitzmann, Stephan H. Böhm, Susanne Reuter

Objective

Microcirculatory disturbances can contribute to organ dysfunction in patients undergoing major surgeries and critical illness. Incident dark field imaging (CytoCam, Braedius Medical BV, Huizen, Netherlands) provides direct visualization of the microcirculation. To utilize this method in daily clinical practice, automated image analysis is essential. This study aims to compare the automated analysis of recorded microcirculation video sequences using CytoCamTools V2 Analysis Manager (Braedius Medical BV) with established manual analysis using Capillary Mapper (Version 1.4.5, University Hospital Münster, Germany) as reference method.

Methods

Sublingual microcirculation video sequences were recorded in patients undergoing laparotomy at four time points (before surgery, 2 and 6 h after surgery, and on the first postoperative day) using incident dark field imaging. Agreement between automated and manual analysis of total vessel density (TVD), perfused vessel density (PVD), and proportion of perfused vessels (PPV) was compared using intraclass correlation (ICC) and Bland–Altman method.

Results

A total of 336 videos from 30 patients were analyzed. The ICC between the two measurement methods was 0.13 for TVD, 0.14 for PVD, and 0.16 for PPV. Bland–Altman analysis showed mean differences (95% limits of agreement) of 10.46 mm/mm² (−1.73–22.65 mm/mm²) for TVD, 8.25 mm/mm² (−9.88–26.39 mm/mm²) for PVD, and − 3.96% (−59.58%–51.65%) for PPV.

Discussion

Automated microcirculatory analysis using the Analysis Manager did not show clinically acceptable agreement with manual analysis using Capillary Mapper. Consequently, automated video analysis using the Analysis Manager does not appear to be a suitable approach.

Trial Registration: ClinicalTrials.gov identifier: DRKS00020264

目的：微循环障碍可导致接受重大手术和危重病人的器官功能障碍。入射暗场成像（CytoCam，Braedius Medical BV，Huizen，Netherlands）可直接观察微循环。要在日常临床实践中使用这种方法，必须进行自动图像分析。本研究旨在比较使用 CytoCamTools V2 分析管理器（Braedius Medical BV）对录制的微循环视频序列进行的自动分析与使用毛细血管绘图仪（1.4.5 版，德国明斯特大学医院）进行的手动分析（作为参考方法）：在四个时间点（术前、术后 2 小时和 6 小时以及术后第一天）使用入射暗场成像技术记录开腹手术患者的舌下微循环视频序列。使用类内相关（ICC）和布兰-阿尔特曼法比较了自动分析与人工分析在总血管密度（TVD）、灌注血管密度（PVD）和灌注血管比例（PPV）方面的一致性：结果：共分析了 30 名患者的 336 个视频。两种测量方法的 ICC 值分别为：TVD 0.13，PVD 0.14，PPV 0.16。Bland-Altman分析显示，TVD的平均差异（95%的一致限）为10.46 mm/mm2（-1.73-22.65 mm/mm2），PVD为8.25 mm/mm2（-9.88-26.39 mm/mm2），PPV为-3.96%（-59.58%-51.65%）：讨论：使用分析管理器进行的自动微循环分析与使用毛细血管绘图仪进行的手动分析没有显示出临床上可接受的一致性。因此，使用分析管理器进行自动视频分析似乎并不是一种合适的方法：试验注册：ClinicalTrials.gov identifier：DRKS00020264.

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引用次数: 0

PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF 抑制 PDE9A 可改善 ZSF1 高频心衰大鼠模型的冠状动脉微血管稀疏度和左心室舒张功能障碍

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-26 DOI: 10.1111/micc.12888

Katie Anne Fopiano, Saltanat Zhazykbayeva, Ibrahim El-Battrawy, Vadym Buncha, William M. Pearson, Davis J. Hardell, Liwei Lang, Nazha Hamdani, Zsolt Bagi

Objective

Heart failure with preserved ejection fraction (HFpEF) commonly arises from comorbid diseases, such as hypertension, obesity, and diabetes mellitus. Selective inhibition of phosphodiesterase 9A (PDE9A) has emerged as a potential therapeutic approach for treating cardiometabolic diseases. Coronary microvascular disease (CMD) is one of the key mechanisms contributing to the development of left ventricular (LV) diastolic dysfunction in HFpEF. Our study aimed to investigate the mechanisms by which PDE9A inhibition could ameliorate CMD and improve LV diastolic function in HFpEF.

Methods and Results

The obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model of HFpEF was employed in which it was found that a progressively developing coronary microvascular rarefaction is associated with LV diastolic dysfunction when compared to lean, nondiabetic hypertensive controls. Obese ZSF1 rats had an increased cardiac expression of PDE9A. Treatment of obese ZSF1 rats with the selective PDE9A inhibitor, PF04447943 (3 mg/kg/day, oral gavage for 2 weeks), improved coronary microvascular rarefaction and LV diastolic dysfunction, which was accompanied by reduced levels of oxidative and nitrosative stress markers, hydrogen peroxide, and 3-nitrotyrosine. Liquid chromatography–mass spectrometry (LC–MS) proteomic analysis identified peroxiredoxins (PRDX) as downregulated antioxidants in the heart of obese ZSF1 rats, whereas Western immunoblots showed that the protein level of PRDX5 was significantly increased by the PF04447943 treatment.

Conclusions

Thus, in the ZSF1 rat model of human HFpEF, PDE9A inhibition improves coronary vascular rarefaction and LV diastolic dysfunction, demonstrating the usefulness of PDE9A inhibitors in ameliorating CMD and LV diastolic dysfunction through augmenting PRDX-dependent antioxidant mechanisms.

目的：射血分数保留型心力衰竭（HFpEF）通常由高血压、肥胖和糖尿病等并发症引起。选择性抑制磷酸二酯酶 9A（PDE9A）已成为治疗心脏代谢疾病的一种潜在疗法。冠状动脉微血管病变（CMD）是导致高频心衰患者左心室舒张功能障碍的关键机制之一。我们的研究旨在探讨抑制 PDE9A 可改善 CMD 和 HFpEF 左心室舒张功能的机制：我们采用肥胖的糖尿病扎克脂肪/自发性高血压心衰 F1 杂交（ZSF1）大鼠作为 HFpEF 模型，发现与瘦弱的非糖尿病高血压对照组相比，逐渐发展的冠状动脉微血管稀疏与左心室舒张功能障碍有关。肥胖 ZSF1 大鼠心脏的 PDE9A 表达增加。用选择性 PDE9A 抑制剂 PF04447943（3 毫克/千克/天，口服，2 周）治疗肥胖 ZSF1 大鼠可改善冠状动脉微血管稀疏和左心室舒张功能障碍，同时降低氧化和亚硝基应激标记物、过氧化氢和 3-硝基酪氨酸的水平。液相色谱-质谱（LC-MS）蛋白质组分析发现，过氧化还原酶（PRDX）是肥胖 ZSF1 大鼠心脏中下调的抗氧化剂，而 Western 免疫印迹显示，PRDX5 蛋白水平在 PF04447943 治疗后显著增加：因此，在人类高密度脂蛋白血症ZSF1大鼠模型中，PDE9A抑制剂可改善冠状动脉血管稀疏和左心室舒张功能障碍，这表明PDE9A抑制剂可通过增强PRDX依赖性抗氧化机制来改善CMD和左心室舒张功能障碍。

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引用次数: 0

Modeling Hemodynamics in Three-Dimensional, Biomimetic, Branched, Microfluidic, Vascular Networks 三维、仿生、分支、微流体血管网络的血液动力学建模。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-25 DOI: 10.1111/micc.12886

Rahul Ramanathan, Andy Borum, David M. Rooney, Sina Y. Rabbany

Objective

Neovascularization has been extensively studied because of its significant role in both physiological processes and diseases. The significance of vascular microfluidic platforms lies in its essential role in recreating an in vitro environment capable of supporting cellular and tissue systems through the process of neovascularization. Biomechanical properties in a tissue engineered system use fluid flow and transport properties to recapitulate physiological systems. This enables mimicry of organ systems which can further personalized and regenerative medicine. Thus, fluid hemodynamics can be used to study these flow patterns and create a system that mimics real physiological pathways and processes. The establishment of stable flow pathways encourages endothelial cells (ECs) ECs to undergo neovascularization. Specifically, the shear stress applied in capillary beds generates the increased proliferation and differentiation of ECs to build larger microcirculatory beds.

Mathematical Framework

Here, we describe a mathematical model that uses branching patterns and vessel morphology to predict hemodynamic parameters in capillary beds.

Results

A retinal capillary bed is used as one-use case of our model to show how the mathematical framework can be used to determine hemodynamic parameters for any microfluidic system.

Conclusion

In doing so, this tool can be altered to be used to supplement emerging research areas in neovascularization.

目的：由于血管新生在生理过程和疾病中的重要作用，人们对其进行了广泛的研究。血管微流控平台的意义在于，它在通过血管新生过程再造能够支持细胞和组织系统的体外环境方面发挥着至关重要的作用。组织工程系统中的生物力学特性利用流体流动和传输特性来再现生理系统。这样就能模仿器官系统，从而促进个性化和再生医学的发展。因此，流体血液动力学可用于研究这些流动模式，并创建一个模仿真实生理途径和过程的系统。建立稳定的流动路径可促进内皮细胞（ECs）发生血管新生。具体来说，毛细血管床中施加的剪切应力会促进内皮细胞的增殖和分化，从而建立更大的微循环床：在此，我们描述了一个数学模型，该模型利用分支模式和血管形态来预测毛细血管床的血液动力学参数：结果：以视网膜毛细血管床作为我们模型的一个使用案例，展示了数学框架如何用于确定任何微流控系统的血液动力学参数：结论：这样做可以改变这一工具，使其用于补充新生血管领域的新兴研究领域。

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引用次数: 0

Microfluctuations in Capillary Lumens Independent of Pericyte Lining Density in the Anesthetized Mouse Cortex 麻醉小鼠皮层毛细血管通明度的微波动与毛细血管内膜密度无关

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-09-16 DOI: 10.1111/micc.12885

Hiroki Suzuki, Juri Murata, Miyuki Unekawa, Iwao Kanno, Yoshikane Izawa, Yutaka Tomita, Kenji F. Tanaka, Jin Nakahara, Kazuto Masamoto

Objective

This study aimed to examine the spatiotemporal coherence of capillary lumen fluctuations in relation to spatial variations in the pericyte lining in the cortex of anesthetized mice.

Methods

Two-photon microscopic angiography data (previously published) were reanalyzed, and spatial variations in capillary diameter fluctuations at rest and in capillary lining with vascular mural cells were measured along capillary centerlines.

Results

Relatively large diameters of the capillaries (5.5 μm) coincided with a dense pericyte lining, while small capillaries (4.3 μm) had a sparse pericyte lining. Temporal variations had a frequency of about 0.1 Hz with an amplitude of 0.5 μm, which were negatively correlated with pericyte lining density. Spatial frequency analysis further revealed a common pattern of spatial variations in capillary diameter and pericyte lining, but temporal variations differed. The temporal variations in capillary lumens were locally distinct from those in neighboring locations, suggesting intrinsic fluctuations independent of the pericyte lining.

Conclusions

Capillary lumens in the brain exhibit slow microfluctuations that are independent of pericyte lining. These microfluctuations could affect the distribution of flowing blood cells and may be important for homogenizing their distribution in capillary networks.

研究目的本研究旨在探讨毛细血管管腔波动的时空连贯性与麻醉小鼠皮层毛细血管内膜的空间变化之间的关系：方法：重新分析了双光子显微血管造影数据（先前已发表），并沿毛细血管中心线测量了静止时毛细血管直径波动的空间变化以及毛细血管内壁细胞的空间变化：结果：毛细血管直径相对较大（5.5 μm）时，毛细血管内壁细胞较密集，而毛细血管直径较小（4.3 μm）时，毛细血管内壁细胞较稀疏。时间变化的频率约为 0.1 Hz，振幅为 0.5 μm，与内膜周细胞密度呈负相关。空间频率分析进一步揭示了毛细血管直径和周细胞衬里的空间变化的共同模式，但时间变化有所不同。毛细血管管腔的局部时间变化与邻近位置的毛细血管管腔的时间变化截然不同，这表明毛细血管管腔的内在波动独立于包膜：结论：大脑中的毛细血管管腔表现出独立于包膜的缓慢微波动。这些微波动可能会影响流动血细胞的分布，并可能对其在毛细血管网络中的均匀分布非常重要。

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引用次数: 0