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PubMed2002

Evidence for non-neurotensin receptor-mediated effects of xenin (1-25)--focus on intestinal microcirculation.

Xenin (1-25) has been detected in various locations in mammalians. It has structural similarities with neurotensin and its intestinal effects are claimed to be mediated by neurotensin receptors. It has been shown to influence gastrointestinal motility. The effects of xenin (1-25) on intestinal microvascular perfusion after ischemia/reperfusion have not been investigated yet. Therefore, the superior mesenteric artery was clamped for 40 min in Wistar rats (n=8). Ten minutes prior to reperfusion, intravenous infusion of xenin (1-25) (5 nmol/kg/h) was started. By means of intravital microscopy, microvascular perfusion in the mucosal layer was assessed. Animals (n=8) with and without clamping of the superior mesenteric artery and infusion of the carrier solution served as controls. After ischemia/reperfusion, xenin (1-25) increased the density of perfused microvessels and the capillary red blood cell velocity compared to ischemic controls. Capillary red blood cell velocity was elevated (p<0.05). Xenin (1-25) improved the heterogeneous distribution of mucosal blood flow during reperfusion demonstrated by an increase of both the perfusion index and the percentage of perfused microvessels. We conclude that the effects of xenin (1-25) on intestinal microcirculation are significantly different from those previously described for neurotensin. A more complex effector mechanism must be postulated that may involve other regulatory peptides and receptors.

Animals↗

PubMed1998

Effects of the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester and aminoethyl-isothiourea on the liver microcirculation in rat endotoxemia.

BACKGROUND/METHODS: The question whether nitric oxide protects or impairs organ perfusion during early endotoxemia has not been completely answered. To evaluate the regulative function of nitric oxide on organ microvascular perfusion and leukocyte accumulation during endotoxemia, we studied the influence of a non-selective nitric oxide inhibitor and a preferential inducible nitric oxide synthase inhibitor (respectively, N(G)-nitro-L-arginine methyl ester and aminoethyl-isothiourea) on liver microcirculation (intravital fluorescence microscopy) in a rat model. RESULTS: Two hours after intraportal injection of lipopolysaccharide (5 mg/kg in 10 min) the rats were randomly treated and received a bolus dose of N(G)-nitro-L-arginine methyl ester (10 mg/kg, n = 7), aminoethyl-isothiourea (10 mg/kg, n = 6) or normal saline, (n = 7). After 1 h, N(G)-nitro-L-arginine methyl ester blockade yielded a higher rate of non-perfused sinusoids than normal saline (27 +/- 2% vs 19 +/- 5%, p < 0.05). LPS-induced leukocyte stagnation in sinusoids was further increased (p < 0.05) in all groups after 1 h treatment, but N(G)-nitro-L-arginine methyl ester clearly accentuated leukocyte accumulation in sinusoids as compared to normal saline (69 +/- 19% vs 16 +/- 4%, p < 0.05). Both modalities of nitric oxide blockade elicited a significant enhancement in the number of leukocytes adherent to the postsinusoidal venules in contrast to normal saline (N(G)-nitro-L-arginine methyl ester 48 +/- 17%, aminoethyl-isothiourea 33 +/- 9% vs normal saline 1 +/- 5%, p < 0.05). CONCLUSIONS: We conclude that complete nitric oxide blockade aggravates lipopolysaccharide-induced hepatic microvascular perfusion failure and enhances leukocyte accumulation, in both sinusoids and post-sinusoidal venules. The preferential inducible nitric oxide synthase inhibitor aminoethyl-isothiourea has a moderate negative effect, favoring leukocyte adhesion in postsinusoidal venules, and its usefulness demands further research, especially concerning its late effects.

Animals↗

PubMedDate not supplied

Norepinephrine in cochlear microcirculation of guinea pigs.

The blood flow in the radiating arteriole through a small cochlear fenestra was recorded with motion pictures in anesthetized guinea pigs, before and after norepinephrine injection into the ipsilateral carotid artery. The flow velocity was determined by measuring the displacement of plasma space running through the radiating arteriole per second. Norepinephrine injection of 0.01 and 0.15 mg/kg increased both flow velocity and arterial blood pressure. The flow velocity increase related directly to the increase in arterial blood pressure. However, a larger norepinephrine dose (1.2 and 2.5 mg/kg) led to transient cessation in flow, which was independent of the blood pressure increase. Dilatation of vessel diameter was always observed with the rise in blood pressure, irrespective of norepinephrine doses. When blood flow in the radiating arteriole stopped after a large norepinephrine injection, the arteriole's vascular lumen was completely obstructed by the aggregated red blood cells. These results suggested that cochlear microcirculation is disturbed by microemboli formed by norepinephrine-induced platelet hyperaggregation.

Animals↗

PubMedDate not supplied

Physiology and pathobiology of the microcirculation.

The delivery of nutrients to the tissues and the removal of waste products from the tissues is made possible by forcing a stream of blood through an arborizing network of microscopic blood vessels that comprise the microcirculation. The rapidity of the flow stream and, therefore, the rate of nutrient delivery to the tissue, is regulated by the automatic adjustment of the caliber of the precapillary arterioles that serve as the primary loci of vascular resistance. Exchange between the blood stream and the parenchymal cells occurs in capillaries and pericytic venules. Pathologic processes such as inflammation, diabetes, ischemia, and hypertension are characterized by abnormalities in microvascular structure and function.

Animals↗

PubMedDate not supplied

A damaged microcirculation contributes to neuronal cell death in Alzheimer's disease.

Alzheimer's disease (AD) involves multiple etiologic factors and a complex pathogenesis. Vascular factors are increasingly implicated in the pathogenesis of AD. In this paper we review evidence that AD brain microvessels are biochemically altered and contribute to neuronal injury and death by release of factors directly injurious to neurons. Our data show that when brain microvessels are "injured" by anoxia they produce high levels of reactive oxygen species. Comparisons of isolated brain microvessels from AD and age-matched controls show specific abnormalities in alpha(1) and beta receptors and in protein kinase C and protein kinase A signaling pathways. In AD but not in controls, the cerebral microcirculation expresses the inflammatory mediator CAP37 and over produces nitric oxide. Finally, we demonstrate that AD microvessels secrete toxic factors that cause neuronal cell death in vitro. These latter experiments showing that AD brain microvessels, in co-culture or vessel-conditioned media, cause lethal injury to neurons in culture, establish a direct link between endothelial cell products and neuronal cell death in this disease.

Alzheimer Disease↗

PubMed2003

High-frequency 3-D color-flow imaging of the microcirculation.

High-frequency (> 20 MHz) ultrasound (US) flow imaging has the potential to be an important tool for assessing microvascular blood flow in superficial tissues noninvasively. In this paper, we describe the development and evaluation of a 3-D US flow imaging system capable of operating at center frequencies in the 20- to 50-MHz range. Flow images are made for tissue volumes of sizes up to 10 mm laterally and 5 mm in depth, permitting a range of scientific and clinical applications. To acquire data sets in a reasonable time, the 2-D sections were derived from data collected with a transducer that was scanning continuously in a direction perpendicular to the beam axis. Due to spectral broadening effects induced by scanning tissue, significant tradeoffs must be made between frame rate, lateral resolution and the minimum detectable blood velocity. 3-D flow images were reconstructed with flow data acquired from a series of adjacent planes. The system was evaluated at a center frequency of 50 MHz, using two PVDF transducers with lateral resolutions of 43 microm and 65 microm and axial resolutions of 66 microm to 72 microm, respectively. Velocity ranges were from below 1 mm/s to 25 mm/s. In vivo validation experiments using the mouse ear demonstrated the ability to follow branching patterns of closely spaced microvessels from 30 microm to 100 microm in diameter. Experiments conducted on mouse tumors successfully imaged microvessel morphology in the tumor microcirculation.

Animals↗

PubMed1997

A high-frequency pulsed-wave Doppler ultrasound system for the detection and imaging of blood flow in the microcirculation.

Previous work with a 40-MHz continuous-wave Doppler ultrasound system has demonstrated the potential of high-frequency Doppler ultrasound (HFD), operating in the frequency range 20-200 MHz, to detect blood flow in the microcirculation. This paper describes a directional, pulsed-wave high-frequency Doppler ultrasound (PW HFD) system that was designed and constructed further to investigate this potential. The PW HFD system electronics have a dynamic range of > 80 dB, a noise floor of 250 nV, a directional isolation of 45 dB and operate over the frequency range 1-200 MHz. The system is tested using a focused PVDF transducer that is tuned for maximum sensitivity at 50 MHz, has a -6 dB lateral beamwidth of 70 microns and -6 dB depth-of-focus of 0.90 mm. This permits the practical use of sample volumes with dimensions 70 microns laterally by 90-900 microns axially. The PW HFD system can operate in duplex mode by either sharing the Doppler transducer or using a second PVDF transducer for imaging. Tests with string and capillary flow phantoms demonstrate that the PW HFD system is capable of detecting velocities on the order of the blood velocities found in the capillaries (0.5 mm/s) and arterioles (5 mm/s) with suitable velocity (30-300 microns/s) and temporal (15-100 ms) resolutions. In vivo measurements demonstrate that PW HFD can detect and measure blood velocities of less than 5 mm/s in arterioles and venules with diameters as small as 20 microns and 35 microns, respectively, using a sample volume of only 70 microns laterally by 150 microns axially. Preliminary experiments with high-frequency colour Doppler (HFCD) and high-frequency power Doppler (HFPD) imaging are also presented.

Animals↗

PubMed2001

Acute effects of whole-body exposure to static magnetic fields and 50-Hz electromagnetic fields on muscle microcirculation in anesthetized mice.

Acute microhemodynamic effects of static and alternating magnetic fields at a threshold level were investigated on modulating the muscle capillary mirocirculation in pentobarbital-anesthetized mice. The skin in a tibialis anterior was circularly removed with 1.5 mm diameter for intravital-microscopic recording of the capillary blood velocity in the tibialis anterior muscle. Fluorescein isothiocyanate (FITC)-labeled dextran (MW 150 kDa) was used for an in vivo fluorescent plasma marker of the muscle capillaries. Following a bolus injection of FITC-dextran solution into the caudal vein, the peak blood velocity in the muscle capillaries was measured prior to, during, and following exposure to static magnetic fields (SMF) or 50-Hz electromagnetic fields (EMF) using a fluorescence epi-illumination system. The whole body of experimental animals, placed on the observing stage of a fluorescence microscope, was exposed to SMF (0.3, 1 and 10 mT) or 50-Hz EMF (0.3 and 1 mT) for 10 min using a specially devised electromagnet. For sham exposure, the electromagnet was not energized. During exposure and post-exposure to SMF of 10 mT, the peak blood velocity significantly increased as compared to sham exposure. After the withdrawal of SMF and 50-Hz EMF of 1 mT, significant similar effects on the blood velocity were present or enhanced. These findings suggest that field intensity of 1 mT might be considered as a threshold level for enhancing muscle microcirculation under pentobarbital-induced hypnosis.

Animals↗

PubMed2002

Ventral burn in rats: an experimental model for intravital microscopic study of microcirculation.

A novel technique of application of controlled ventral scald burn to rodent, whose back is inaccessible because of preburn preparation, is described. Boiling water is applied across a polyethylene membrane that partially envelops the subject. The technique is simple, economical, reproducible and allows intravital microscopic study of microcirculation in a remote muscular bed before and after burn injury.

Abdominal Injuries↗

PubMed1998

Microcirculation of the distal humeral epiphyseal cartilage: implications for post-traumatic growth deformities.

The purpose of this study was to determine if there is an anatomic basis for development of the avascular necrosis infrequently seen after elbow trauma. The microcirculation to the distal humeral epiphyseal cartilage was studied in 38 elbow joints from 19 skeletally immature individuals. The findings of this study were as follows: (1) Vascularity is centripetal within the epiphyseal cartilages of the capitellum, trochlea, and medial and lateral epicondyles. Because of this vascularity pattern, it is not easy for avascular necrosis to develop after trauma within these epiphyses. (2) Vascularity is longitudinal in the epiphyseal cartilage between the capitellum and trochlea. The longitudinal vessels appear susceptible to fractures around the elbow in childhood. (3) A rich vascular network exists in the olecranon fat pad, and a vascular arch forms from the vascular network adjacent to the distal humeral epiphyseal cartilage. The vascular arch sends several large branches into the epiphyseal cartilage in a vertical fashion. Disruption of either the longitudinal intraosseous vasculature (vertical extraosseous blood supply) or the vascular arch in more than 2 places may lead to selective avascular necrosis of the epiphyseal cartilage between the capitellum and trochlea. These findings suggest vascular compromise as a possible explanation for "fish-tail" deformities seen as sequellae of different fracture patterns.

Female↗

PubMed2001

Tetrahydrobiopterin improves endothelial dysfunction in coronary microcirculation in patients without epicardial coronary artery disease.

OBJECTIVES: We aimed to determine whether intracoronary supplementation with nitric oxide (NO) synthase co-factor tetrahydrobiopterin (BH4) improves NO-dependent coronary microvascular dilation in patients with coronary risk factors but no significant organic stenosis. BACKGROUND: Impaired coronary microvascular dilator reserve attributable to endothelial dysfunction plays an important role in the regulation of coronary blood flow (CBF). METHODS: Fifteen patients were measured for CBF (Doppler-wire and quantitative coronary angiography). Stimulated release of NO in the coronary microcirculation was evaluated by percent increase in CBF (%ACBF) at graded doses of intracoronary acetylcholine (1, 3, 10 and 30 microg/min). Measurements were repeated after intracoronary co-infusion of BH4 (4 mg/min) and acetylcholine. RESULTS: The patients were divided into two groups on the basis of CBF responses to acetylcholine: those with "diminished" (%deltaCBF <300%, n = 8) and "normal" (%deltaCBF >300%, n = 7) flow responses. Tetrahydrobiopterin significantly (p < 0.0001) improved acetylcholine-induced increases in CBF in patients with diminished flow responses, but exerted no effect in those with normal flow responses. Among the 15 studied patients, the magnitude of flow improvement by BH4 was inversely correlated with baseline flow responses (p < 0.02). Microvascular dilator response to direct NO donor (isosorbide dinitrate) was not affected by BH4. CONCLUSIONS: We demonstrated for the first time that intracoronary BH4 improved acetylcholine-induced microvascular dilator responses in patients with endothelial dysfunction in vivo. Thus, supplementation with BH4 may be a novel therapeutic means to increase NO availability for patients with coronary microvascular disease.

Acetylcholine↗

PubMed1999

Flow dynamics of QW7437, a new dodecafluoropentane ultrasound contrast agent, in the microcirculation: microvascular mechanisms for persistent tissue echo enhancement.

OBJECTIVES: The purpose of this study was to test the hypothesis that a subgroup of QW7437 microbubbles, dodecafluoropentane-based ultrasound contrast microspheres, resides for prolonged periods in the microvasculature. BACKGROUND: QW7437 produces echo enhancement in myocardium which may persist relatively longer than opacification in the left ventricular cavity. The mechanism for this persistent enhancement remains unknown. METHODS: The transit of fluorescently labeled erythrocytes was examined by fluorescence intravital microscopy in the microvessels in five rat mesenteries. Ten rats were used to observe the behavior of fluorescently labeled QW7437 microbubbles in the mesenteric microcirculation. RESULTS: There was no significant change in erythrocyte velocity in the arterioles and venules after the administration of QW7437 microbubbles (0.05 ml/kg) preactivated by negative hydrodynamic pressure. Of 552 microbubbles observed in four arterioles and five capillaries, 549 (99.5%) passed without stoppage (> or = 0.1 s stoppage); only one stopped transiently in arteriole and two in capillaries, each for <0.5 s. Sixty-five of 478 microbubbles (13.6%) observed in six postcapillary venules 11 to 30 microm in diameter and 24 of 408 microbubbles (5.9%) in four venules 31 to 50 microm in diameter stopped transiently (0.1 to 180 s) with an attachment to venular endothelium; the remaining microbubbles passed through the venules without stoppage. CONCLUSIONS: Prolonged survival as microbubbles in the circulation and transient stoppage of a subgroup of microbubbles in the microvasculature, particularly in venules, are potential mechanisms for the persistent tissue echo enhancement by QW7437 microbubbles during contrast echocardiography.

Animals↗

PubMed1994

Effect of leg elevation on the skin microcirculation in chronic venous insufficiency.

PURPOSE: Leg elevation is advised in the treatment of venous disease associated with edema. We have used laser Doppler fluxmetry to assess the effects of leg elevation on the skin microcirculation. METHODS: Fifteen patients with lipodermatosclerosis caused by chronic venous insufficiency and 15 control subjects were studied. Measurements were made from the liposclerotic skin of patients and 8 cm above the medial malleolus in control subjects. Laser Doppler flux, blood cell velocity, and concentration of moving blood cells were recorded with the subject lying in the supine position and after elevating the foot 30 cm above the heart level. RESULTS: In subjects in the horizontal position, the resting laser Doppler flux was significantly higher in patients with lipodermatosclerosis than in control subjects (median difference 63 arbitrary units; 95% confidence interval: 36, 108). This difference was due to a higher concentration of moving blood cells in the patient group (median difference 6.5 arbitrary units; 95% confidence interval: 3.4, 9). The blood cell velocity was not statistically significant between the two groups. On leg elevation, there was a substantial increase in the laser Doppler flux in the patient group; the median percentage increase in flux was 45% (p < 0.01). This was due to an increase in blood cell velocity; the median percentage increase was 41% (p < 0.01). There was no corresponding change in the concentration of moving blood cells. The results in the control group showed a similar trend but have not reached statistical significance. CONCLUSION: We conclude that limb elevation enhanced the microcirculatory flow velocity in liposclerotic skin of patients with chronic venous insufficiency.

Aged↗

PubMed1997

Morphometric assessment of the dermal microcirculation in patients with chronic venous insufficiency.

PURPOSE: Ultrastructural assessments of the dermal microcirculation in patients with chronic venous insufficiency have been limited to qualitative morphologic descriptions of venous ulcer edges or venous stasis dermatitis. The purpose of this investigation was to quantify differences in endothelial cell structure and local cell type with emphasis on leukocytes and their relationship to arterioles, capillaries, and postcapillary venules (PCVs). METHODS: Two 4.0 mm punch biopsies were obtained from areas of dermal stasis skin changes in the gaiter region of the leg, as well as from noninvolved areas of skin in the ipsilateral thigh, from 35 patients: CEAP class 4 (11 patients), class 5 (9 patients), class 6 (10 patients), and five normal skin biopsies from patients without chronic venous insufficiency. Electron microscopy was performed on sections at 6700x and 23,800x magnification. At 6700x endothelial cell thickness was determined, and the number of fibroblasts, leukocytes, and mast cells were recorded relative to their proximity to arterioles, capillaries, and PCVs. Similarly, at 23,800x endothelial cell vesicle density, interendothelial junctional widths, and basal lamina thickness (cuff width) were measured. Preliminary evaluation for the presence of transforming growth factor-beta 1 (TGF-beta 1) was performed on three patients using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Quantitative measurements demonstrated increased mast cell content for class 4 and 5 patients around arterioles and PCVs and increased macrophage numbers for class 6 patients around PCVs (p < 0.05). Fibroblasts were the most common cells observed; however, no differences were demonstrated between groups. No differences were observed in interendothelial junctional widths or vesicle densities in arterioles, capillaries, or PCVs. Basal lamina thickness was increased only at the capillary level (p < 0.05). The results of RT-PCR for TGF-beta 1 messenger RNA were positive in the three patients studied. CONCLUSIONS: Our data suggest that (1) mast cells play a role in the pathogenesis of chronic venous insufficiency; (2) the effects of mast cells, macrophages, or both may be mediated in part by TGF-beta 1; and (3) capillary cuff formation is not associated with widened interendothelial gap junctions, but may be a result of enhanced vesicular transport rate or conformational changes in the interendothelial glycocalyx.

Aged↗

PubMedDate not supplied

Gastric mucosal integrity: gastric mucosal blood flow and microcirculation. An overview.

The stomach is in a state of continuous exposure to potentially hazardous agents. Hydrochloric acid together with pepsin constitutes a major and serious threat to the gastric mucosa. Reflux of alkaline duodenal contents containing bile and pancreatic enzymes are additional important injurious factors of endogenous origin. Alcohol, cigarette smoking, drugs and particularly aspirin and aspirin-like drugs, and steroids are among exogenous mucosal irritants that can inflict mucosal injury. The ability of the stomach to defend itself against these noxious agents has been ascribed to a number of factors constituting the gastric mucosal defense. These include mucus and bicarbonate secreted by surface epithelial cells, prostaglandins, sulfhydryl compounds and gastric mucosal blood flow. The latter is considered by several researchers to be of paramount importance in maintaining gastric mucosal integrity. The aim of this paper is to review the experimental and clinical data dealing with the role of mucosal blood flow and in particular the microcirculation in both damage and protection of the gastric mucosa.

Acids↗

PubMed1997

Targeting of the tumor microcirculation by photodynamic therapy with a synthetic porphycene.

9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a chemically pure substance with fast pharmacokinetics and superior photodynamic properties in vitro as compared to Photofrin. In this study the pharmacokinetics, photodynamic efficacy and tissue localization of ATMPn were investigated in vivo. Amelanotic melanomas (A-Mel-3) were implanted in dorsal skin fold chambers fitted to Syrian Golden hamsters. Fluorescence kinetics of ATMPn (1.4 mumol kg-1 b.w.i.v.; n = 8) were monitored by intravital microscopy. Quantitative measurements of fluorescence intensity were carried out by digital image analysis. For tumor growth studies 1.4 mumol kg-1 was injected 24 h (n = 3), 3 h (n = 3), 1 min (n = 6) and 2.8 mumol kg-1 1 min (n = 6) before PDT (Laser (630 nm) or lamp (600-750 nm), 100 mW cm-2, 100 J cm-2). Tumor volume was measured for 28 d. Solid tumors (n = 3) were excised 1 min after injection of ATMPn (2.8 mumol kg-1) and cryostat sections (20 mm) were analyzed by confocal laser scanning microscopy (CLSM) for tissue localization of the dye. Maximal fluorescence (mean +/- S.E.) arose in the tumor (94 +/- 7%) and surrounding host tissue (67 +/- 5%) 30 s post injection followed by a rapid decrease. Hardly any fluorescence was detectable 12 h after administration. Only PDT 1 min after injection of ATMPn was effective yielding 3/6 complete remissions (2.8 mmol kg-1, laser) and 6/6 complete remissions (2.8 mumol kg-1, lamp), respectively. One minute after injection the dye is primarily localized in the vascular wall of normal and tumor vessels as shown by CLSM. PDT at a time, when the dye is localized primarily in the tumor microcirculation, exhibits the best tumor killing effects showing that vascular targeting is effective in treating solid malignant tumors. ATMPn in liposomes makes administration and light irradiation in one session possible due to its fast pharmacokinetics. Thus, using ATMPn as a photosensitizer may provide more flexibility to perform PDT after surgical exploration and debulking as adjuvant therapy.

Animals↗

PubMedDate not supplied

Intravital microscopy for the study of mouse microcirculation in anti-inflammatory drug research: focus on the mesentery and cremaster preparations.

Intravital microscopy is an extremely useful tool used as a qualitative and quantitative way of observing leukocyte-endothelial cell interactions in-vivo. This present article reviews the methods of the technique of intravital microscopy, in particular focussing on the mesentery and cremaster preparations. It focuses on how to actually carry out the experiments required to directly observe and localize the changes in the function of the microcirculation. Where necessary the reader is asked to refer to a selection of highly acclaimed publications, which should enable the reader to truly appreciate, and if necessary perform, the technique of intravital microscopy.

Animals↗

PubMed2003

Microcirculation in insulin resistance and diabetes: more than just a complication.

The microvascular bed is an anatomical entity which is governed by specific, highly regulated mechanisms which are closely adapted to the specific function of each vascular segment. Among those, small arteriolar vasomotion and capacity of small vessels to constrict in response to physical and humoral stimuli play a major role. Other processes of importance for the adequacy of nutritive perfusion are haemorheological properties of whole blood and red cells, adhesiveness of leukocytes and capillary permeability. This review provides some description of these phenomena, how they impact on organ function and how they appear in diabetes. Metformin, as a unique example among the drug arsenal, exerts various effects preferentially at the level of smallest vessels (arterioles, capillaries, venules). This review summarises our actual knowledge and includes several new data showing its high potential for reducing microvascular dysfunction. Most of these unique properties have also been demonstrated in non-diabetic animals or humans, suggesting they are intrinsic to the drug and not secondary to diabetic metabolic improvement. A particular focus is put on the relevance of metformin's capacity to stimulate slow wave arteriolar vasomotion and improve functional capillary density, whereby nutritive flow can be re-established. Finally, the implication of microcirculation in other aspects of insulin resistance and diabetes, such as macroangiopathy and metabolic control, is discussed and strengthens the concept of a broad involvement of microvascular dysfunction in these diseases as well as the potential interest of introducing adapted treatment early in the history of a patient's diabetes.

Arterioles↗