scholarly journals Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells

2019 ◽  
Vol 115 (13) ◽  
pp. 1918-1932 ◽  
Author(s):  
Dean P J Kavanagh ◽  
Adam B Lokman ◽  
Georgiana Neag ◽  
Abigail Colley ◽  
Neena Kalia

Abstract Aims Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating heart in vivo. Haematopoietic stem/progenitor cells (HSPCs) offer a potential therapy but little is known about their homing dynamics at a cellular level and whether they protect coronary microvessels. This study used intravital microscopy to image the anaesthetized mouse beating heart microcirculation following stabilization. Methods and results A 3D-printed stabilizer was attached to the ischaemia–reperfusion injured (IRI) beating heart. The kinetics of neutrophil, platelet and HSPC recruitment, as well as functional capillary density (FCD), was imaged post-reperfusion. Laser speckle contrast imaging (LSCI) was used for the first time to monitor ventricular blood flow in beating hearts. Sustained hyperaemic responses were measured throughout reperfusion, initially indicating adequate flow resumption. Intravital microscopy confirmed large vessel perfusion but demonstrated poor transmission of flow to downstream coronary microvessels. Significant neutrophil adhesion and microthrombus formation occurred within capillaries with the latter occluding them, resulting in patchy perfusion and reduced FCD. Interestingly, ‘patrolling’ neutrophils were also observed in capillaries. Haematopoietic stem/progenitor cells readily trafficked through the heart but local retention was poor. Despite this, remarkable anti-thromboinflammatory effects were observed, consequently improving microvascular perfusion. Conclusion We present a novel approach for imaging multiple microcirculatory perturbations in the beating heart with LSCI assessment of blood flow. Despite deceptive hyperaemic responses, increased microcirculatory flow heterogeneity was seen, with non-perfused areas interspersed with perfused areas. Microthrombi, rather than neutrophils, appeared to be the major causative factor. We further applied this technique to demonstrate local stem cell presence is not a pre-requisite to confer vasculoprotection. This is the first detailed in vivo characterization of coronary microcirculatory responses post-reperfusion injury.

2018 ◽  
Vol 45 (2) ◽  
pp. 0207006
Author(s):  
李晨曦 Li Chenxi ◽  
陈文亮 Chen Wenliang ◽  
蒋景英 Jiang Jingying ◽  
范颖 Fan Ying ◽  
杨婧孜 Yang Jingzi ◽  
...  

2021 ◽  
Vol 11 (22) ◽  
pp. 10969
Author(s):  
E Du ◽  
Shuhao Shen ◽  
Anqi Qiu ◽  
Nanguang Chen

Laser speckle imaging has been an indispensable tool for visualizing blood flow in biomedical applications. We proposed a novel design of the laser speckle imaging system, which combines confocal illumination and detection with various speckle analysis methods. The system can be operated by three imaging modes. One is surface illumination laser speckle contrast imaging (SI-LSCI) and the other two are line scan temporal speckle contrast imaging (LS-TSCI) and line scan spatial speckle contrast imaging (LS-SSCI). The experimental results of flow phantoms have validated the mixture model, which combines the Lorentzian and Gaussian models to describe the simultaneous existence of both Brownian motions and ordered flow. Our experimental results of in vivo chick embryos demonstrate that LS-SSCI maintains high temporal resolution and is less affected by motion artifacts. LS-SSCI can provide better image quality for in vivo imaging blood chick embryos than LS-TSCI. Furthermore, the experiential results present that LS-SSCI can detect and quantify the blood flow change during vascular clipping, and shows great potential in diagnosing vascular diseases, such as angiosclerosis, angiostenosis, or angiemphraxis.


2011 ◽  
Vol 300 (2) ◽  
pp. F319-F329 ◽  
Author(s):  
Niels-Henrik Holstein-Rathlou ◽  
Olga V. Sosnovtseva ◽  
Alexey N. Pavlov ◽  
William A. Cupples ◽  
Charlotte Mehlin Sorensen ◽  
...  

Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50–100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic techniques for extracting the desired data and for examining them for evidence of nephron synchronization. Synchronized TGF oscillations were detected in pairs or triplets of nephrons. The amplitude and the frequency of the oscillations changed with time, as did the patterns of synchronization. Synchronization may take place among nephrons not immediately adjacent on the surface of the kidney.


2017 ◽  
Vol 111 ◽  
pp. 49-59 ◽  
Author(s):  
Mohammad Zaheer Ansari ◽  
Eun-Jeung Kang ◽  
Mioara D. Manole ◽  
Jens P. Dreier ◽  
Anne Humeau-Heurtier

2018 ◽  
Vol 12 (1) ◽  
pp. e201800100 ◽  
Author(s):  
Wenzhi Lv ◽  
Yang Wang ◽  
Xiao Chen ◽  
Xiaoxi Fu ◽  
Jinling Lu ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ewa Grudzińska ◽  
Monika Modrzejewska

Myopia is the most common refractive error and the subject of interest of various studies assessing ocular blood flow. Increasing refractive error and axial elongation of the eye result in the stretching and thinning of the scleral, choroid, and retinal tissues and the decrease in retinal vessel diameter, disturbing ocular blood flow. Local and systemic factors known to change ocular blood flow include glaucoma, medications and fluctuations in intraocular pressure, and metabolic parameters. Techniques and tools assessing ocular blood flow include, among others, laser Doppler flowmetry (LDF), retinal function imager (RFI), laser speckle contrast imaging (LSCI), magnetic resonance imaging (MRI), optical coherence tomography angiography (OCTA), pulsatile ocular blood flowmeter (POBF), fundus pulsation amplitude (FPA), colour Doppler imaging (CDI), and Doppler optical coherence tomography (DOCT). Many researchers consistently reported lower blood flow parameters in myopic eyes regardless of the used diagnostic method. It is unclear whether this is a primary change that causes secondary thinning of ocular tissues or quite the opposite; that is, the mechanical stretching of the eye wall reduces its thickness and causes a secondary lower demand of tissues for oxygen. This paper presents a review of studies assessing ocular blood flow in myopes.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chiraz El-Aouni ◽  
Franziska Globisch ◽  
Achim Pfosser ◽  
Georg Stachel ◽  
Rabea Hinkel ◽  
...  

Recruitment of endothelial progenitor cells to the sites of ischemia is a prerequisite for efficient therapeutic neovascularization via vasculogenesis. Chemokines play a major role in the homing of EPCs at the ischemic vasculature, a mechanism fading in chronic ischemia. To overcome this limitation, we constructed an artificial adhesion molecule consisting of a GPI-anchor, a fractalkine-backbone and an SDF-1 head (SDF-1-fra-GPI), which was applied for enhanced recruitment of embryonic EPCs (eEPCs: CXCR4++, Tie2++, Thrombomodulin++, CD34-, MHCI-, vWF inducible, eNOS inducible) in vitro and in vivo . Methods: In a flow chamber adhesion assay, Control plasmids (pcDNA or GPI-SDF-1 cDNA) were compared to the SDF-1-fra-GPI construct for eEPC recruitment 24h after liposomal transfection of rat endothelial cells. In vivo, in rabbits (n=5 per group) at day 7 (d7) after femoral artery excision, 1 mg of the SDF-1-fra-GPI or eGFP cDNA was transfected into the ischemic limb. At d9, ischemic hindlimbs were retroinfused with 5x10 6 eEPCs. Angiography was performed for collateral quantification and frame count score at d9 and d37 (% of d9), capillary density was assessed via PECAM-1-staining (capillaries/muscle fiber = c/mf). Results: In vitro, eEPC adhesion (16±12 cells/field) was increased to a higher extent by SDF-1-fra-GPI (79±13) than SDF1-GPI (54±8) or control vector (37±8). In vivo , eEPC adhesion in the ischemic hindlimb after SDF-1-fra-GPI transfection compared to mock transfection (30±3 vs. 9±1 cells/field). Whereas capillary density was unaffected (1.66±0.30 SDF-1-Fra-GPI vs. 1.56±0.29 eEPCs), collateral growth (152±10% SDF-1-fra-GPI vs. 124±13%) as well as perfusion score (198±17% SDF-1-fra-GPI vs.160±6% eEPCs) further increased after SDF-1-fra-GPI transfection (controls: 1.24±0.12 c/mf, collaterals 105±8%, perfusion score 112±11%). We conclude that recruitment of EPCs expressing CXCR4 (the SDF-1 receptor) may benefit from pre-treatment of the recipient vasculature with SDF-1-Fra-GPI, an artificial adhesion molecule. This approach might be valuable for enhancing EPC recruitment in the scenario of therapeutic neovascular-ization of chronic ischemic syndromes.


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