Due to its strategic anatomical position, the endothelium is constantly exposed to the different risk factors for atherosclerosis. During the last decade it has become clear that hypertension profoundly affects endothelial function. Depending on the form of hypertension, endothelium-dependent relaxation is impaired in most vascular beds. In spontaneous hypertension, the production of nitric oxide, which in endothelial cells is formed from L-arginine via the constitutively expressed enzyme endothelial nitric oxide synthase, represents the main mediator of endothelium-dependent vasodilation and seems to be enhanced. On the other hand, the release of endothelium-dependent contracting factors such as prostaglandin H2 and thromboxane A2 have been demonstrated in this model of hypertension. Similar results have been obtained in the forearm circulation of patients with essential hypertension. In contrast, in models of salt-sensitive hypertension no release of vasoconstrictor prostanoids can be found indicating a decreased production of nitric oxide. Thus, in spontaneous hypertension an increased production of nitric oxide seems to occur, which is ineffective due to either the simultaneous release of endothelium-dependent vasoconstrictors and/or inactivation of nitric oxide, or due to anatomical changes such as hypertension-induced intimal thickness which inhibits its action on vascular smooth muscle cells. In summary, in hypertension, endothelium-dependent vasodilation is blunted and the endothelial L-arginine nitric oxide pathway is altered. These changes seem to represent a consequence rather than a cause of hypertension.
Despite many theories, the initiating circumstances for the development of atherosclerosis remain obscure. The development of animal models of atherosclerosis was based upon the different theories of the origins of atherosclerosis which suggested that it originates at the intimal surface of the vessel. A more recent model of atherosclerosis involves perivascular manipulation of the vessel by positioning of a hollow silastic collar around the artery. In this model, several of the features seen in early human atherosclerosis are generated within a period of 7 days. It is hypothesized that arterial wall hypoxia following occlusion of the vasa vasorum may be the initial lesion of atherosclerosis, and hence that in some cases atherosclerosis is a disease of the outer layers of the arterial wall.
INTRODUCTION:Biological signals like arterial blood pressure (ABP) and electrocardiograms are usually displayed in a linear fashion. The often very complex structure may, however, be better described by phase space plots and time-delayed vectors, enabling an advantageous display of the dynamics contained in the signal. The potentials of such a display were investigated during elective aortic aneurysm repair, where profound haemodynamic changes frequently occur.METHOD:The peripheral volume pulse was recorded at a digit using noninvasive near infrared photoplethysmography (NIRP). All patients (n = 20, mean age 72.8 years) were invasively monitored using arterial and Swan Ganz catheters. The ABP signal was continuously recorded with a computer (sample rate 128 Hz). Two different phase space plots, [x(t), y(t + 8/128 s) and x(t), d(x(t + 8/128 s) - x(t))/dt] were calculated for the NIRP and the ABP signals and continuously displayed. The stability was subjectively assessed and the fractal dimension calculated using the 'Hausdorff dimension'. The correlation between stability, fractal dimension and frequently used parameters of patient monitoring were investigated.RESULTS:All patients included in the study had an uncomplicated operation. Cardiac index (CI) and oxygen delivery (DO2) increased, and systemic vascular resistance (SVR) decreased following declamping of the aorta. The ABP signal was generally more stable. After declamping of the aorta, 14 of 16 NIRP signals became unstable, and 9 of 14 ABP signals destabilised. The time required for stabilisation of the signal varied between the individual patients. Thirty minutes after declamping, 11 of 12 ABP signals were stable, whereas 3 out of 9 NIRP signals still revealed an unstable pattern. A fractal dimension was calculated by box counting, which revealed a linear regression over two orders of magnitude in a log-log plot (Hausdorff dimension between 1.19 and 1.71). The mean fractal dimension for NIRP was significantly higher than that of the ABP signal. On clamping and declamping of the aorta, a trend to a higher fractal dimension (p = 0.08) was observed for both signals analysed. No correlation was observed between the fractal dimension and ABP, SVR index, CI, DO2 index and oxygen consumption.DISCUSSION:The dynamic changes of the signals were emphasised when they were displayed as phase space plots calculated by time-delayed vectors. The time series of the signal revealed a fractal dimension, and the observed increase at the critical time points of the operation, where the need for cardiovascular regulation is most pronounced, support the contention that a physiological system based on non-linear behaviour may enable a rapid response to haemodynamic challenges. An on-line display of phase space plots calculated by time-delayed vectors may in future provide a valuable method of monitoring for high-risk patients.
This technical report describes the production and installation of a newly developed, one-piece, light-weight (0.6 g) access plexiglass chamber for the dorsal skin fold of the mouse.
The transcapillary and interstitial diffusion of intravenously administered sodium fluorescein is used as a marker for capillary permeability. Fluorescein diffusion has been expressed by different parameters with reported coefficients of variation of 14-20%. Aim of the present study is to select a parameter which combines excellent reproducibility with the potential for discriminating insulin-dependent diabetic patients from healthy subjects. We performed three experiments to assess day-to-day reproducibility: 5 healthy subjects were measured twice, 1 healthy subject was measured 6 times and 1 subject with insulin-dependent diabetes mellitus was measured 5 times. We averaged the relative fluorescence light intensity (IREL(t)] from dye arrival until a certain time point [IAV(t)], instead of using the relative intensity at one time point. IAV (7 min) showed markedly improved reproducibility, expressed as geometric mean of the coefficients of variation of the three separate experiments: 10%. In addition, a group of 12 insulin-dependent diabetic subjects was compared with 12 healthy control subjects. Median IAV (7 min) was 69.5% (95% CI: 65.3-78.1%) in the diabetic subjects and 54.9% (95% CI: 52.1-60.0%) in the control subjects (p < 0.001). Since IAV (7 min) combines excellent reproducibility with a good discriminating power, we advise its use in further studies.
The systemic effect of heparin fractions with mean molecular masses of 2.5, 5.0 and 16.4 kD on angiogenesis induced by vascular endothelial growth factor isoform 165 was studied using the truly quantitative rat mesenteric-window angiogenesis assay. The angiogenic treatment with 5 ml of VEGF165 at 480 pM was given intraperitoneally on days 0-4 and heparin fractions were given subcutaneously on days 0-13; animals were sacrificed on day 14. As the overlaps between the molecular mass distributions of the three fractions were relatively small, they essentially represent three different populations of heparin molecules. The doses of the heparins given were equal in terms of weight, but different in terms of the number of molecules and biologic activity. Angiogenesis was assessed in terms of vascularized area (VA), a measurement of microvascular spatial extension, and microvascular length (MVL), a measurement of microvascular density, using technically independent variables and image analysis. The total microvascular length was computed from VA x MVL. Treatment with the 5.0-kD fraction suppressed angiogenesis significantly in statistical terms compared with treatment with 2.5- and 16.4-kD heparins and the saline in controls. Interestingly, the 2.5-kD heparin fraction which was used here has previously been shown statistically significantly to suppress angiogenesis mediated by basic fibroblast growth factor in the same experimental system. Our data thus suggest that the systemic angiosuppressive effect of heparin in different mammalian angiogenic reactions is distinctly related to structural features such as molecular size.
Although microvasculitis is one of the more common manifestations of systemic lupus erythematosus, there is no data on the hemodynamics of the skin microcirculation in such patients. The combination of dynamic capillaroscopy measuring capillary blood cell velocity (CBV) and laser Doppler fluxmetry (LDF) was used to simultaneously evaluate the nutritional and the total skin microcirculation in the fingers of 24 consecutive patients with SLE, using normal matched subjects as controls.The nutritional skin flow, as assessed by the CBV, was significantly impaired in patients, as compared with controls, both at rest (p = 0.001) and during postocclusive reactive hyperemia (p = 0.006). By contrast, no differences were observed in total skin microcirculation, as assessed by LDF (n.s.). There was no significant correlation between hemodynamic parameters and the presence of Raynaud's phenomenon, morphological capillary changes or anticardiolipine antibodies. There was no correlation between the magnitude of the alteration of the capillary blood flow and capillary morphological abnormalities, suggesting that the microvascular damage might be caused by different pathophysiological mechanisms.
Effects of low- and high-intensity endurance training on the capillary luminal diameter and number were studied morphometrically in the rat plantaris muscle. Male Wistar-Imamichi rats were divided into three groups: sedentary control group (Cont, n = 9), low-intensity (running speed of 20 m/min) training group (T-20, n = 8) and high-intensity (running speed of 40 m/min) training group (T-40, n = 7). Rats in both training groups were subjected to each treadmill running program for 60 min/day, 5 days/week for 9 weeks. After 9 weeks of training, citrate synthase activity significantly increased in T-40 compared with Cont, but did not change in T-20. All morphometric parameters with respect to capillary and muscle fiber area were determined in the perfusion-fixed plantaris muscle. The mean muscle fiber areas in both T-20 and T-40 were similar to that in Cont. The capillary-to-fiber ratios were significantly higher in T-20 (2.28 +/- 0.06) and T-40 (2.29 +/- 0.06) than in Cont (2.00 +/- 0.07). The number of capillaries with a small luminal diameter (2-4 microns) was significantly higher in T-20 than in Cont. In contrast, T-40 had a significantly higher number of capillaries with a large luminal diameter (8-10 microns) compared with Cont. This study indicates that endurance training induces changes in the capillary luminal diameter as well as capillary number, and that the adaptive response of the capillary luminal diameter to endurance training depends on the training intensity.
Research Articles| November 25 2008 Calibration Problems for Dimensional Measurements of Microvessel Using TV Methods Subject Area: Cardiovascular System Q. Hu; Q. Hu Division of Angiology, Department of Medicine, Inselspital, Bern, Switzerland Search for other works by this author on: This Site PubMed Google Scholar F. Mahler; F. Mahler Division of Angiology, Department of Medicine, Inselspital, Bern, Switzerland Search for other works by this author on: This Site PubMed Google Scholar M. Ouanella M. Ouanella Division of Angiology, Department of Medicine, Inselspital, Bern, Switzerland Search for other works by this author on: This Site PubMed Google Scholar International Journal of Microcirculation (1997) 17 (2): 97. https://doi.org/10.1159/000179214 Article history Received: September 17 1996 Accepted: March 03 1997 Published Online: November 25 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Q. Hu, F. Mahler, M. Ouanella; Calibration Problems for Dimensional Measurements of Microvessel Using TV Methods. International Journal of Microcirculation 1 February 1997; 17 (2): 97. https://doi.org/10.1159/000179214 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsInternational Journal of Microcirculation Search Advanced Search Article PDF first page preview Close Modal Keywords: Capillaroscopy, Calibration, Dimension, Digital image processing 1997Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
A modified technique of vital capillary microscopy with intraarterial application of Na-fluorescein has been introduced in the study of nutritional skin microcirculation to assess skin microcirculation of different diabetic patients, comprising one group without neurocutaneous complications (group 2; n = 9), one suffering only from neuropathy (group 3; n = 9) and one with trophic skin lesions in the contralateral foot (group 4; n = 8), all without macroangiopathy, compared to healthy controls (group 1; n = 9). Femoroarterial injection of small boli (10 mg) of Na-fluorescein allowed repeated investigation of the dye appearance times (AT) and capillary-filling times of forefoot skin capillaries within small periods of time before, during and after reactive hyperemia. At rest, AT was significantly shorter in patients of group 4 (16.8 +/- 4.4 s; p < 0.05) compared with groups 1-3 (34.3 +/- 12.8; 31.7 +/- 11.7 and 35.9 +/- 15.3 s). Fifteen seconds after the end of arterial occlusion, dye propagation to the skin was markedly accelerated in groups 1-3 (19.8 +/- 14.0; 14.4 +/- 7.6 and 18.7 +/- 10.6 s, respectively; p < 0.001), but prolonged in group 4 (18.4 +/- 7.4 s). After 10 min, the values at rest were reestablished. No differences between the four groups were found concerning capillary density and morphology. It is concluded that the development of skin lesions in diabetic patients without significant macroangiopathy may be favored by hyperperfusion and impaired vasoregulation. Intraarterial dye injection presents a valuable tool to assess dynamic alterations of the microcirculation at the level of skin capillaries.
We have recently shown that the purified micronized flavonoid fraction (90% diosmin and 10% hesperidin) Daflon 500 mg attenuates reperfusion injury in the striated skin muscle of the hamster. Herein, we report on the action of Daflon 500 mg on postischemic macromolecular leakage of FITC-dextran 150 kD provoked by tourniquet ischemia. Intravital fluorescence microscopy was used for analysis of macromolecular leakage in the microcirculation model of the hamster. A tourniquet ischemia of 4 h duration was induced followed by reperfusion. Animals were treated by gavage of Daflon 500 mg (n = 6) for 8 days at a daily dose of 30 mg kg(-1) body weight. Control animals received equivalent volumes of the vehicle (5% Arabic gum solution, n = 6). Measurements of the microcirculatory parameters were made before induction of ischemia and at 0.5, 2 and 24 h of reperfusion. After induction of ischemia, macromolecular leakage from postcapillary venules was significantly enhanced in vehicle-treated animals. Treatment with Daflon 500 mg significantly attenuated macromolecular leakage of FITC-dextran 150 kD. Preliminary data from a histomorphometric analysis (n = 3/experimental group) indicated that the number of emigrated (extravascular) leukocytes after ischemia reperfusion was markedly reduced in Daflon 500 mg-treated animals as compared to controls. These data indicate that Daflon 500 mg prevents leakage of the macromolecular tracer FITC-dextran 150 kD from postcapillary venules after postischemic reperfusion, presumably through an inhibitory action on the emigration of activated leukocytes.
Synergetic concepts allow to identify emergent coordination phenomena between interacting physiological systems, for example between the cutaneous microcirculation, the sympathetic nervous system and the cardiac and pulmonary systems. The temporal patterns (oscillations of various frequencies) that are found in the data obtained with laser-Doppler anemometers (LDA; e.g. Periflux 2 used in the study) can be investigated by simultaneous recording of photoplethysmographic data obtained in the identical region of interest, as well as in cutaneous regions treated with vasoparalytic procedures which permit to record the dynamics of the arterial system. These strategies were applied to studies in the cutaneous microcirculation (volar side of the index fingers) as well as to mucosal microcirculation (maxillar gingiva) in healthy subjects and in patients suffering from autonomic dysfunction (cutaneous microcirculation) or gingivitis. By this procedure, it could be corroborated that - contrary to popular notions - the temporal fluctuations in the LDA records do not necessarily reflect myogenic vasomotion, but can have multiple causes. In a confirming recent study [Schmid-Schönbein et al., J Auton Nerv Syst, 57, 136-140, 1996], we have demonstrated that the LDA fluctuations under conditions of normal ambient temperature and hand position most likely reflect neurogenic vasoconstriction. Under exceptional conditions, different patterns emerge. Prolonged exposure to ambient temperature (18 degrees C) leads to marked vasoconstriction, with occasional vasodilator escape ('miniature hunting reaction'). Normal subjects under gravitational load and in warm environment (28 degrees C ambient) silence their neurogenetic vasoconstriction reactions, which allows sinusoidal vasomotion to dominate. A similar phenomenon is seen in neuropathic patients at 21-24 degrees C (presumably due to structural defects). Fluctuations in LDA signal taken from the healthy gingiva are entrained to arterial, those taken from inflamed gingiva to respiratory activity. The theory and practice of nonlinear analysis is discussed, and data compression procedures allowing to portray characteristic temporal patterns for future diagnostic procedures are presented.
In inflammation, cells interact with extracellular matrices or neighboring cells by a spatio-temporal intervention pattern of specific cell surface receptors and adhesion molecules. Resident cells of the injured tissue communicate with circulating effector cells by cytokines and direct cell-cell contact. These cytokines stimulate expression of the adhesion molecules ICAM-1, VCAM-1, and E- and P-selectin on endothelial cell surfaces and upregulate beta 2-integrins and ICAM-1 on luminal leukocytes. White blood cells then adhere to the activated endothelial cells, migrate through the vessel wall, and penetrate areas of infection or tissue damage. The basis for a cellular immune response is formed by the interaction between T lymphocytes and antigen-presenting cells amplified by adhesion molecule LFA-1,2,3 to ICAM-1 binding.
For the first time measurements of lymph flow velocities in cutaneous microlymphatics of patients with lymphedema were performed and compared with healthy subjects. Flow velocity in single lymphatic skin capillaries was measured using fluorescence video microscopy after subepidermal microinjection of FITC-dextran 150,000 in 15 healthy volunteers and 16 patients with primary lymphedema. Initial filling of the lymphatic capillary network was fast with significantly higher mean velocities in patients with primary lymphedema than in healthy controls (890 +/- 43 vs. 550 +/- 390 microns/s, p < 0.05). The resting velocities were not significantly different between controls and patients (10.3 +/- 4.1 vs. 16.6 +/- 13.9 microns). In 12 out of the 16 lymphedema patients cutaneous backflow of the fluorescent contrast medium from deeper invisible lymphatics was observed. In 4 of these patients rhythmic reflux with a mean frequency of 1.4 +/- 0.5 cycles/min was measured by video densitometry in microlymphatics with a significantly (p < 0.01) enhanced diameter. Mean flow velocity (Vp) in these precollectors was significantly increased compared to the resting velocities (p < 0.01). On the basis of these results the hypothesis is advanced that rhythmic cutaneous backflow originates from intrinsic contractions of deeper lymph collector segments and is transmitted to the superficial microlymphatics through incompetent connecting channels. This newly recognized mechanism appears to be an important factor for the pathophysiology of lymphedema.
A small-bowel manometry tube was supplied with two single-fiber microprobes, which recorded blood flow in the proximal small intestine by the laser-Doppler flowmetry (LDF) technique. In all experiments, saline was infused intravenously as control during the first migrating motor complex (MMC) cycle, and a drug or another saline control given intravenously during the second MMC cycle. Recordings were performed during phase 1 of MMC, i.e. when motor pattern showed quiescence. Adrenaline increased blood perfusion values by 140% in proximal duodenum and 95% in distal duodenum. The alpha 2-adrenoceptor agonist clonidine decreased the corresponding values by 34 and 25%, respectively, while oxymetazoline decreased perfusion by 33 and 44% at the same levels. The beta-adrenoceptor agonist isoprenaline increased blood perfusion values by 172% in the proximal duodenum and 194% in the distal duodenum, whereas the antagonist propranolol decreased the corresponding values by 45 and 52%, respectively. In a separate group of subjects, propranolol was given after adrenaline. The increase in blood perfusion regularly seen after adrenaline was blocked after propranolol administration. In conclusion, our findings validate semi-invasive LDF technique for studies of hemodynamics in human small intestine under basal motor conditions and in drug-induced blood flow changes.
The chorioallantoic membrane (CAM) of the chick embryo represents an in vivo model to evaluate microvascular function during the sequential phases of endothelial proliferation (angiogenesis), cytodifferentiation, and senescence. The principal focus of this study was to characterize microvascular barrier functions of the CAM endothelium during its nonproliferating, aging phase (senescence). A graded series of fluorescein isothiocyanate (FITC) dextrans served to index macromolecular selectivity of the senescent capillary endothelium. Extravasation of FITC dextrans 40 and 150 was restricted, while FITC dextran 10 progressively accumulated within the intercapillary interstitia during 15-min perfusion periods. Endothelial vesicle densities were greater in the first- and second-order pre- and first- order postcapillary endothelia (28 +/- 8/micron2) than those recorded for the capillary endothelium (8 +/- 3/micron2). Junctional cleft lengths (luminal to abluminal distances), on the other hand, were greater in the capillary endothelium (1.08 +/- 0.50 microns) than those recorded for the second-order pre- and postcapillaries (0.46 +/- 0.03 micron). Junctional cleft widths were segmentally uniform (20 nm) in the microvascular units. That permselectivity of the segmental microvascular endothelia was homogeneous is ultrastructurally consistent with the uniform junctional cleft widths rather than the heterogeneous cleft lengths and vesicle densities. The CAM serves as the principal respiratory exchange surface of the embryo. Thus, maintenance of colloid oncotic balance across the microvascular endothelium is likely critical to gaseous exchange. The retention of a selective barrier during the senescent phase of the CAM endothelium serves to support this concept.
Intravital microscopy of the hamster cheek pouch microvasculature was used for in vivo studies of the effects of diltiazem (calcium antagonist, group I), prazosin (alpha 1-adrenergic receptor antagonist, group III), rauwolscine (alpha 2-adrenergic receptor antagonist, group V), phenylephrine (alpha-adrenergic receptor agonist, group VII) and isoproterenol (beta-adrenergic receptor agonist, group IX) in a concentration range of 10(-9)-10(-5) M and their combination with 10(-7) M of buflomedil (groups II, IV, VI, VIII and X) on mean arteriolar internal diameter and spontaneous vasomotion. All drugs were applied topically. Vasomotor activity was studied in 270 arterioles (internal diameter range 20.0-75.0 microns) of 60 preparations. Diltiazem dose dependently increased the microvascular diameter and reduced and ultimately abolished the vasomotion frequency and amplitude. Addition of buflomedil did not significantly change the vasodilation evoked by diltiazem and potentiated its depressive effect on vasomotion frequency and amplitude. Prazosin dose-dependently increased the arteriolar diameter and reduced the vasomotion frequency and amplitude. Addition of buflomedil potentiated both the vasodilation elicited by prazosin and the reduction in vasomotion frequency and amplitude. Rauwolscine tended to elicit vasoconstriction at lower concentrations (10(-9) and 10(-8) M) and vasodilation at higher concentrations (10(-5) M) and significantly reduced the vasomotion frequency and amplitude. Addition of buflomedil potentiated both the vasodilation and the reduction in vasomotion frequency, but tended to increase the vasomotion amplitude. Phenylephrine significantly decreased the mean arteriolar internal diameter, moderately decreased the vasomotion frequency and did not significantly change the vasomotion amplitude. Addition of buflomedil totally blocked the vasoconstriction elicited by phenylephrine, potentiated the reduction in vasomotion frequency and amplitude when combined with lower concentrations of phenylephrine (10(-9)-10(-7) M) and restored the vasomotion frequency and amplitude when combined with higher concentrations of phenylephrine (10(-6) and 10(-5) M). Isoproterenol significantly increased the mean arteriolar diameter and reduced the vasomotion frequency and amplitude. Addition of buflomedil did not significantly change either the vasodilation or the reduction in vasomotion frequency and amplitude. The effects observed with buflomedil on the hamster cheek pouch microcirculation further support its properties as a competitive inhibitor of alpha-adrenergic receptors, not selective for either the alpha 1- or alpha 2-adrenergic receptor subtype, and as a weak calcium antagonist.
There are no reports on the autologous transplantation and patency of microvessels in living tissue. We autotransplanted microvessel fragments (Mvf) labeled with DiI-Ac-LDL into the peritoneum and then observed the peritoneum for 7 days postoperatively with a conventional fluorescence or laser scanning confocal microscope. We illustrated a neomicrovascular network of transplanted Mvf labeled with DiI-Ac-LDL in the peritoneum with both a fluorescence and a laser scanning confocal microscope. Furthermore, we demonstrated not only the existence of erythrocytes in the lumina of transplanted DiI-Ac-LDL-labeled Mvf, but also the presence of India ink perfused through the superior mesenteric artery in the lumina of the labeled Mvf. This evidence directly suggests that transplanted Mvf can survive and proliferate to connect adjacent microvascular branches of the superior mesenteric artery in the very early phase of wound healing. Moreover, these findings imply that implantation of Mvf in the microvascular ischemic circulatory tissue might accelerate angiogenesis to reconstitute a new microvascular network connecting to the nearby host microvascular system, which ultimately improves microcirculation.
