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Pulmonary hypertension (PH) is a chronic, progressive condition in which respiratory muscle dysfunction is a primary contributor to exercise intolerance and dyspnea in patients. Contractile function, blood flow distribution, and the hyperemic response are altered in the diaphragm with PH, and we sought to determine whether this may be attributed, in part, to impaired vasoreactivity of the resistance vasculature. We hypothesized that there would be blunted endothelium-dependent vasodilation and impaired myogenic responsiveness in arterioles from the diaphragm of PH rats. Female Sprague-Dawley rats were randomized into healthy control (HC, n = 9) and monocrotaline-induced PH rats (MCT, n = 9). Endothelium-dependent and -independent vasodilation and myogenic responses were assessed in first-order arterioles (1As) from the medial costal diaphragm in vitro. There was a significant reduction in endothelium-dependent (via acetylcholine; HC, 78 ± 15% vs. MCT, 47 ± 17%; P < 0.05) and -independent (via sodium nitroprusside; HC, 89 ± 10% vs. MCT, 66 ± 10%; P < 0.05) vasodilation in 1As from MCT rats. MCT-induced PH also diminished myogenic constriction (P < 0.05) but did not alter passive pressure responses. The diaphragmatic weakness, impaired hyperemia, and blood flow redistribution associated with PH may be due, in part, to diaphragm vascular dysfunction and thus compromised oxygen delivery which occurs through both endothelium-dependent and -independent mechanisms. [Display omitted] • Pulmonary hypertension (PH) induces diaphragm dysfunction and blood flow redistribution. • Diaphragm arteriolar responsiveness is impaired in PH rats. • Both endothelial function and vascular smooth muscle function are blunted with PH. • Diaphragm vascular dysfunction may predicate respiratory muscle failure in PH. [ABSTRACT FROM AUTHOR]

Laser Doppler Flowmetry (LDF) is a non-invasive technique for the assessment of tissue blood flow, but increased reproducibility would facilitate longitudinal studies. The aim of the study was to assess the interday reproducibility of Laser Doppler Flowmetry (LDF) at rest, at elevated local temperatures, and with the use of the vasodilator Methyl Nicotinate (MN) in six interconnected protocols for the measurement of the blood supply to the microvascular bed of the gingiva. Ten healthy volunteers were included. Interweek LDF measurements with custom-made acrylic splints were performed. Six protocols were applied in separate regions of interest (ROI): 1; basal LDF, 2; LDF with thermoprobe 42 °C, 3; LDF with thermoprobe 45 °C, 4; LDF with thermoprobe 42 °C and MN, 5; LDF with thermoprobe 45 °C and MN and 6; LDF with MN. Intra-individual reproducibility was assessed by the within-subject coefficient of variation (wCV) and the intraclass correlation coefficient (ICC). Basal LDF measurements demonstrated high reproducibility with wCV 11.1 in 2 min and 10.3 in 5 min. ICC was 0.9 and 0.92. wCV after heat and MN was 4.9–10.3 and ICC 0.82–0.93. The topically applied MN yielded increased blood flow. This is the first study evaluating the reproducibility of basal LDF compared to single or multiple vasodilatory stimuli in gingiva. Multiple collector fibers probe and stabilizing acrylic splints are recommended. Vasodilatory stimulation showed a tendency toward higher reproducibility. Furthermore, MN yields vasodilation in gingiva. • This study provides feasible protocols for future longitudinal studies of gingival microcirculation. • A high intra-individual basal LDF reproducibility can be achieved with multiple collector fibers probe and acrylic splint. • A tendency of higher reproducibility was seen when vasodilatory stimulation was applied, • Methyl Nicotinate can be used as a simple method to achieve vasodilation on gingiva [ABSTRACT FROM AUTHOR]

Blood flow in the gingiva, comprising the interdental papilla as well as attached and marginal gingiva, is important for maintaining of gingival function and is modulated by risk factors such as stress that may lead to periodontal disease. Marked blood flow changes mediated by the autonomic (parasympathetic and sympathetic) nervous system may be essential for gingival hemodynamics. However, differences in autonomic vasomotor responses and their functional significance in different parts of the gingiva are unclear. We examined the differences in autonomic vasomotor responses and their interactions in the gingiva of anesthetized rats. Parasympathetic vasodilation evoked by the trigeminal (lingual nerve)-mediated reflex elicited frequency-dependent blood flow increases in gingivae, with the increases being greatest in the interdental papilla. Parasympathetic blood flow increases were significantly reduced by intravenous administration of the atropine and VIP antagonist. The blood flow increase evoked by acetylcholine administration was higher in the interdental papilla than in the attached gingiva, whereas that evoked by VIP agonist administration was greater in the attached gingiva than in the interdental papilla. Activation of the cervical sympathetic nerves decreased gingival blood flow and inhibited parasympathetically induced blood flow increases. Our results suggest that trigeminal-parasympathetic reflex vasodilation 1) is more involved in the regulation of blood flow in the interdental papilla than in the other parts of the gingiva, 2) is mediated by cholinergic (interdental papilla) and VIPergic systems (attached gingiva), and 3) is inhibited by excess sympathetic activity. These results suggest a role in the etiology of periodontal diseases during mental stress. • Prominent parasympathetic vasodilation exists in the interdental papilla. • Cholinergic and VIPergic system contributes to gingival parasympathetic vasodilation. • Excess sympathetic activity inhibits gingival parasympathetic vasodilation. [ABSTRACT FROM AUTHOR]

To measure non-invasively retinal venous blood flow (RBF) in healthy subjects and patients with retinal venous occlusion (RVO). The prototype named AO-LDV (Adaptive Optics Laser Doppler Velocimeter), which combines a new absolute laser Doppler velocimeter with an adaptive optics fundus camera (rtx1, Imagine Eyes®, Orsay, France), was studied for the measurement of absolute RBF as a function of retinal vessel diameters and simultaneous measurement of red blood cell velocity. RBF was measured in healthy subjects (n = 15) and patients with retinal venous occlusion (RVO, n = 6). We also evaluated two softwares for the measurement of retinal vessel diameters: software 1 (automatic vessel detection, profile analysis) and software 2 (based on the use of deep neural networks for semantic segmentation of vessels, using a M2u-Net architecture). Software 2 provided a higher rate of automatic retinal vessel measurement (99.5 % of 12,320 AO images) than software 1 (64.9 %) and wider measurements (75.5 ± 15.7 μm vs 70.9 ± 19.8 μm, p < 0.001). For healthy subjects (n = 15), all the retinal veins in one eye were measured to obtain the total RBF. In healthy subjects, the total RBF was 37.8 ± 6.8 μl/min. There was a significant linear correlation between retinal vessel diameter and maximal velocity (slope = 0.1016; p < 0.001; r 2 = 0.8597) and a significant power curve correlation between retinal vessel diameter and blood flow (3.63 × 10−5 × D2.54; p < 0.001; r 2 = 0.7287). No significant relationship was found between total RBF and systolic and diastolic blood pressure, ocular perfusion pressure, heart rate, or hematocrit. For RVO patients (n = 6), a significant decrease in RBF was noted in occluded veins (3.51 ± 2.25 μl/min) compared with the contralateral healthy eye (11.07 ± 4.53 μl/min). For occluded vessels, the slope between diameter and velocity was 0.0195 (p < 0.001; r 2 = 0.6068) and the relation between diameter and flow was Q = 9.91 × 10−6 × D2.41 (p < 0.01; r 2 = 0.2526). This AO-LDV prototype offers new opportunity to study RBF in humans and to evaluate treatment in retinal vein diseases. • There is no standard technique for the measurement of retinal blood flow • Values of retinal blood flow are significantly lowered in cases of retinal vein occlusion and the relationship between retinal vein diameters and flow of occluded vessels is modified when compared to normal eyes. • We developed a prototype named AOLDV which allows simultaneous measurements of retinal vessel diameters using AO technology and blood velocities with bidirectional laser Doppler velocimetry • This technique may be useful for the follow-up of eyes with retinal vascular disease [ABSTRACT FROM AUTHOR]

Laser doppler flowmetry (LDF) allows non-invasive assessment of microvascular functions. The combination of LDF with an occlusion functional test enables study of post-occlusive reactive hyperemia (PORH), providing additional information about vasomotor function, capillary blood flow reserve, and the overall reactivity of the microvascular system. To identify early alterations of PORH variables in the skin of a rat in hemorrhagic shock (HS). Male Wistar rats (n = 14) weighing 400–450 g were anesthetized with a combination of tiletamine/zolazepam (20 mg/kg) and xylazine (5 mg/kg). The animals breathed on their own, and were placed on a heated platform in the supine position. A PE-50 catheter was inserted into the carotid artery to measure the mean arterial pressure (MAP). The optical probe of the Laser Doppler device was installed on the plantar surface of the hind limb of a rat; a pneumatic cuff was applied proximal to the same limb. The occlusion time was 3 min. The following physiological variables were measured at baseline and 30 min after blood loss: MAP, mmHg; mean cutaneous blood flow (M, PU); cutaneous vascular conductance (CVC = M/MAP); peak hyperemia (M max , PU) and maximum cutaneous vascular conductance (CVC max) during PORH. In the HS group (n = 7), 30 % of the estimated blood volume was taken within 5 min. There was no blood loss in the group of sham-operated animals (Sham, n = 7). The results are presented as Me [25 %;75 %]. The U-Mann-Whitney criterion was used to evaluate intergroup differences. Differences were considered statistically significant at p < 0.05. The groups did not differ at baseline. Blood loss led to a significant decrease in MAP (43 [31;46] vs. 94 [84;104] mmHg), M (11.5 [16.9;7.8] vs 16.7 [20.2;13.9]) and M max (18.1 [16.4;21.8] vs. 25.0 [23.0;26.2]) in the HS group compared to the Sham group, respectively. At the same time, both CVC (0.25 [0.23;0.30] vs. 0.16 [0.14;0.21]) and CVC max (0.55 [0.38;0.49] vs 0.24 [0.23; 0.29]) increased after blood loss in the HS group compared to the Sham group. Arterial blood gas analysis revealed metabolic lactic acidosis in the HS group. In this rat model of HS, alterations in cutaneous blood flow are manifested by a decrease in perfusion (M) and the intensity of PORH (M max) with a simultaneous increase in vascular conductance (CVC and CVC max). • Experimental acute blood loss under general anesthesia causes severe hypotension and metabolic lactic acidosis. • Alterations in cutaneous blood flow are manifested by a decrease in resting perfusion and peak hyperemia with an increase in CVC. • PORH variables can be used as markers of vascular dysfunction in animal models of shock and other disease. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid – compared to crystalloid – therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2–860.1) vs. 595.6 (496.3–694.8) arbitrary units, p =.007). There were no important differences in renal (509.7 (427.2–592.1) vs. 442.1 (361.2–523.0) arbitrary units, p =.286) and hepatic (604.7 (507.7–701.8) vs. 548.7 (444.0–653.3) arbitrary units, p =.376) microcirculatory blood flow between groups. Pigs assigned to colloid – compared to crystalloid – therapy also had less small intestinal, but not renal and hepatic, histopathological damage. Goal-directed isooncotic hydroxyethyl-starch colloid – compared to balanced isotonic crystalloid – therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials. Legend to graphical abstract: Goal-directed colloid – compared to crystalloid – therapy improved small intestinal microcirculatory blood flow (Flux (a.u.)) in pigs with aortic-cross-clamping-induced ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials. a.u. = arbitrary units, HES = hydroxyethyl-starch. Adapted and modified with permission from: Behem et al., Microvasc Res 2022, DOI: https://doi.org/10.1016/j.mvr.2022.104383. [Display omitted] • Colloids improved small intestinal microcirculatory blood flow in ischemia/reperfusion. • Colloids also led to less small intestinal histopathological damage. • There were no important differences of renal and hepatic microcirculatory blood flow. [ABSTRACT FROM AUTHOR]

The complexity of microvascular circulation has led to the development of advanced imaging techniques and biomimetic models. This study developed a multifaceted microfluidic-based microdevice as an in vitro model of microvasculature to replicate important geometric and functional features of in vivo perfusion in mice. The microfluidic device consisted of a microchannel for blood perfusion, mirroring the natural hierarchical branching vascular structures found in mice. Additionally, the device incorporated a steady gradient of oxygen (O 2) which diffused through the polydimethylsiloxane (PDMS) layer, allowing for dynamic blood oxygenation. The assembled multi-layered microdevice was accompanied by a dual-modal imaging system that combined laser speckle contrast imaging (LSCI) and intrinsic signal optical imaging (ISOI) to visualize full-field blood flow distributions and blood O 2 profiles. By closely reproducing in vivo blood perfusion and oxygenation conditions, this microvasculature model, in conjunction with numerical simulation results, can provide quantitative information on physiologically relevant hemodynamics and key O 2 transport parameters that are not directly measurable in traditional animal studies. [Display omitted] • Microfluidic device was developed as an in vitro model of microvasculature. • Microchannel design was directly derived from realistic in vivo vascular geometries. • Oxygen gradient was coordinated with blood flow in the microdevice via gas diffusion. • Dual-modal system combines LSCI and ISOI for blood flow and oxygen profile imaging. • The replica can provide comparable hemodynamics and O 2 transport behavior as in vivo. [ABSTRACT FROM AUTHOR]

Vascular impairment is closely related to increased mortality in chronic kidney disease (CKD). The objective of this study was to assess impairments in the regulation of peripheral microvascular perfusion in patients with CKD based on time-frequency spectral analysis of resting near-infrared spectroscopy (NIRS) signals. Total hemoglobin (tHb) concentration and tissue saturation index (TSI) signals were collected using NIRS for a continuous 5 mins at 10 Hz from the forearm of 55 participants (34 CKD including 5 with end-stage renal disease, and 21 age-matched control). Continuous wavelet transform-based spectral analysis was used to quantify the spectral amplitude within five pre-defined frequency intervals (I, 0.0095–0.021 Hz; II, 0.021–0.052 Hz; III, 0.052–0.145 Hz; IV, 0.145–0.6 Hz and V, 0.6–2.0 Hz), representing endothelial, neurogenic, myogenic, respiratory and heartbeat activity, respectively. CKD patients showed lower tHb average spectral amplitude within the neurogenic frequency interval compared with controls (p = 0.014), consistent with an increased sympathetic outflow observed in CKD. CKD patients also showed lower TSI average spectral amplitude within the endothelial frequency interval compared with controls (p = 0.046), consistent with a reduced endothelial function in CKD. These findings demonstrate the potential of wavelet analysis of NIRS to provide complementary information on peripheral microvascular regulation in CKD. • Wavelet analysis of resting NIRS in skeletal muscle quantifies diminished peripheral microvascular regulation in CKD. • Reduced tHb neurogenic spectral amplitude reflects increased sympathetic outflow and reduced neurovascular control in CKD. • Reduced endothelial spectral amplitude of tissue saturation in CKD is suggestive of impaired endothelial function. [ABSTRACT FROM AUTHOR]

Abstract Present work concerns the pulsatile blood flow of two-fluid model through porous blood vessels under the effect of radially varying viscosity. Blood is modeled as two-phase fluid model consisting a core region by non-Newtonian (Herschel-Bulkley) fluid and a plasma region modeled as Newtonian fluid. No slip condition has been used on wall and pressure gradient is taken as periodic function of time. Up to first order approximate solutions of governing equations are obtained using perturbation approach. A comparative analysis for relative change in flow resistance between our model and previously studied single and two-fluid models without porous layer near wall has also been done. The wall of the blood vessel is composed by a thin Brinkman (porous) layer. The stress jump condition has been imposed on fluid-porous interface. Analytical expressions for the velocity profile, flow rate, wall shear stress and flow resistance have been obtained for different regions and the effect of plasma layer thickness, varying viscosity, yield stress, permeability and viscosity ratio parameter on the flow variables are pictorially discussed. It is perceived that values of flow rate for two-fluid model with porous region near wall is higher in comparison to two-fluid model without porous region near wall. Present study reveals a significant impact of glycocalyx layer on blood flow through blood vessels with a porous layer near wall. Highlights • In the present work, pulsatile nature of blood flow of two-fluid model through porous blood vessels under the effect of radially varying viscosity has been done. • The combined effect of plasma layer thickness (and hence porous layer thickness), varying viscosity parameters, permeability and viscosity ratio parameter on hemodynamical quantities have been pictorially analyzed and compared with constant viscosity model. • The viscosity ratio parameter (and hence porosity of arterial wall) affects the plug core radius (and hence the yield plane location). • Due to presence of porous region near wall, there is slight phase difference in flow rate and flow resistance between two-fluid model with and without porous region near wall which completely agrees with Tiwari and Deo [A. Tiwari, S. Deo, Pulsatile flow in a cylindrical tube with porous walls: Applications to blood flow, Journal of Porous Media 16(4) (2013) 335-340] approach. • The outcome of above work shows a significant impact of the viscosity ratio parameter and permeability arising due to existence of glycocalyx layer near wall on various hemodynamical quantities such as rate of flow and resistance offered against the flow. [ABSTRACT FROM AUTHOR]

Abstract The flow through curved microvessels has more realistic applications in physiological transport phenomena especially in blood flow through capillary and microvessels. Motivated by the biomicrofluidics applications, a mathematical model is developed to describe the blood flow inside a curved microvessel driven by electroosmosis. In addition to this flow, the channel experiences electric double layer phenomenon due to zeta potential about −25 mV. Lubrication theory and Debye-Hückel approximation are employed to obtain an analytical solution for electric potential function. Computations of stream function, axial velocity, volume flow rate, and pressure rise are computed through low zeta potentials. The electroosmotic flow behaviour is governed by two dimensionless parameters: Helmholtz-Smoluchowski velocity and Debye-Hückel parameter. It is also examined that, how curvature affects the blood flow driven by the electroosmosis. Furthermore, the salient features of flow characteristics and trapping phenomena are presented. The results indicate that pressure gradient and wall shear stress reduce with increasing the curvature effects however the trapping is more with high curvature of the microvessel. The observations also indicate promising features of micromixer, micro-peristaltic pumps, and organ-on-a-chip devices. They may further be exploited in diagnosis/mixing of samples, and haemodialysis respectively. Highlights • A mathematical model is developed to analyze the blood flow through micro curve channel. • The effects of zeta potential and electric double layer on flow mechanism are simulated. • The effect of curvature on flow characteristics and trapping phenomenon is computed. • Pressure gradient and wall shear stress are examined under the influence of physical parameters. • This model may also be applicable to design the organ-on-a-chip devices for more precise diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary alveolar septal capillaries receive their perfusion from a web of larger surrounding acinar vessels. Using 4 μm diam. Latex particles, we showed that positive pressure ventilation narrowed the acinar vessels as evidenced by venous 4 μm particle concentrations and perfusate flows <50% of particle concentrations in negative pressure ventilated lungs. We aimed to understand the effects of positive and negative pressure ventilation on flows of larger particles through the lung. Isolated, ventilated rat lungs (air, transpulmonary pressures of 15/5 cm H2O, 25 breaths/min) were perfused with a hetastarch solution at Ppulm art/PLA pressures of 10/0 cm H2O. Red latex 7 μm (2.5 mg, 4.8 × 106) or 15 μm (2.5 mg, 5.5 × 105) particles were infused into each lung during positive or negative pressure ventilation. An equal number of green particles was infused 20 min later. Flows through lungs infused with 7 μm and 15 μm particles were not different from flows through lungs infused with 4 μm particles (p = 0.811). Venous particle concentrations of 7 μm particles relative to infused particles were lower in positive pressure lungs (0.03 ± 0.03%) compared to negative pressure lungs (0.17 ± 0.12%) (p = 0.041). Venous particle concentrations of 15 μm particles were not different between positive (2.3 ± 1.9%) and negative (3.3 ± 1.8%) pressure ventilation (p = 0.406). Together with our previous study, we conclude that 4 μm and 7 μm particles both enter acinar vessels but that the 7 μm particles are too large to flow through those vessels. In contrast, we conclude that 15 μm particles bypass the acinar vessels, flowing instead through larger intrapulmonary vessels to enter the venous outflow. These findings suggest that intrapulmonary vessels are organized as a web that allows bypass of the acinar vessels by large particles and, that these bypass vessels are not compressed by positive pressure ventilation. Highlights • The acinar circulation is organized as a web around the alveoli and allows bypass. • The acinar circulation is compressed by positive pressure ventilation. • The circulation that supplies it is a web not compressed by positive pressure ventilation. [ABSTRACT FROM AUTHOR]

Abstract Previous studies have suggested a possible relationship between age-related changes to human gingival hemodynamics and periodontal disease. However, firmly establishing this has been difficult because of a lack of suitable tools. Our study investigated whether a non-invasive laser speckle flowgraphy (LSFG)-based 2-dimensional technique could be used to assess maxillary anterior gingival blood flow under resting conditions. In total, 124 healthy male volunteers aged between 22 and 69 years were included in the study and delineated into young (Y; 22–37 years, n = 45), middle-aged (M; 38–53 years, n = 43), and elderly groups (E; 54–69 years, n = 36). The differences in gingival hemodynamics were compared among age groups and pulse waveform analysis performed to calculate blood flow indices, mean blur rate (MBR), gingival vascular conductance (MBR/mean blood pressure [MBP]), and three pulse waveform parameters (acceleration time index [ATI], falling rate, and blowout time [BOT]). Although no statistically significant differences were observed in the MBR of the three age groups, vascular conductance (MBR/MBP) was lower in groups M and E compared to group Y and correlated negatively with age. ATI and falling rates were also significantly higher in group E relative to group Y, whereas average BOT was significantly lower. All of the assessed parameters correlated with age. These data suggest that there are age-related decreases in the ability to maintain blood flow in the human maxillary anterior gingiva under resting conditions which may impact the likelihood of periodontal disease. Highlights • There is a suggested link between gingival blood flow, age, and periodontal disease. • Laser speckle flowgraphy was used to assess gingival blood flow in volunteers. • Vascular conductance and blowout time were lower in older than in young groups. • Acceleration time indices and falling rates were higher in older individuals. • Our study confirms age-related differences in resting gingival blood flow. [ABSTRACT FROM AUTHOR]

Abstract We report the development of a 1300 nm swept-source optical coherence tomography (SS-OCT) system specifically designed to perform OCT imaging and optical microangiography (OMAG) in rat eyes in vivo and its use in evaluating the effects of intraocular pressure (IOP) elevation on ocular circulation. The swept laser is operated in single longitude mode with a 90 nm bandwidth centered at 1300 nm and 200 kHz A-line rate, providing remarkable sensitivity fall-off performance along the imaging depth, a larger field of view of 2.5 × 2.5 mm2 (approximately 35°), and more time-efficient imaging acquisition. The advantage of the SS-OCT/OMAG is highlighted by an increased imaging depth of the entire posterior thickness of optic nerve head (ONH) and its surrounding vascular anatomy, to include, for the first time in vivo , the vasculature at the scleral opening, allowing visualization of the circle of Zinn-Haller and posterior ciliary arteries (PCAs). Furthermore, the capillary-level resolution angiograms achieved at the retinal and choroidal layers over a larger field of view enable a significantly improved quantification of the response of vascular area density (VAD) to elevated IOP. The results indicate that reduction in perfusion of the choroid in response to elevated IOP is delayed compared to that seen in the retina; while choroidal VAD doesn't reach 50% of baseline until ~70 mmHg, the same effect is seen for the retinal VAD at ~60 mmHg. The superior image quality offered by SS-OCT may allow more comprehensive investigation of IOP-related ocular perfusion changes and their pathological roles in glaucomatous optic nerve damage. Highlights • 1300nm swept-source OCT (SS-OCT) offers superb ability to image rodent eyes with enhanced imaging depth beyond sclera. • SS-OCT is useful in evaluating the effects of intraocular pressure (IOP) elevation on ocular circulation. • SS-OCT provides structural and blood flow imaging of the retina, choroid, and outer choroid. • At higher IOP, previously unattainable in vivo imaging of the circle of Zinn-Haller and PCAs are feasible. [ABSTRACT FROM AUTHOR]

Abstract Timely diagnostics of microcirculatory system abnormalities, which are the most severe diabetic complications, is one of the major problems facing modern health care. Functional abnormalities manifest themselves earlier than the structural ones, and therefore their assessment is the issue of primary importance. In this study Laser Doppler flowmetry, a noninvasive technique for the cutaneous blood flow monitoring, was utilized together with local temperature tests and wavelet analysis. The study of the blood flow in the microvascular bed of toes was carried out in the control group of 40 healthy subjects and in two groups of 17 type 1 and 23 type 2 diabetic patients. The local temperature tests demonstrated that the diabetic patients have impaired vasodilation in response to local heating. The tendency for impaired low frequency pulsations of the blood flow associated with endothelial and neurogenic activities in both diabetes groups was observed. Local thermal tests induced variations in perfusion and its spectral characteristics, which were different in the groups under study. In our opinion, the obtained preliminary results can be a basis for further research and provide a deeper understanding of pathological processes that drive microvascular abnormalities caused by diabetes mellitus. Highlights • Local thermal test affects averaged and spectral components of cutaneous blood flow. • Spectral pattern of blood flow oscillation caused by local heating differs in controls and DM. • DM is accompanied by impaired vasodilation and lower response of myogenic vascular tone. • The results give deeper insight into the development of vascular abnormalities in diabetes. [ABSTRACT FROM AUTHOR]

Purpose To investigate cutaneous sensory nerve contribution to hyperaemia following chronic shear stress training. Methods Eleven males underwent a shear stress intervention (forearm occlusion 5 s, rest 10 s) for 30 min, 5 times·week −1 for 6 weeks on one arm, the other was an untreated control. Skin blood flow was measured using laser-Doppler flowmetry, and sensory nerve function was assessed with and without blockade with EMLA cream in response to 3 levels of local heating (39, 42, and 44 °C) and post-occlusive reactive hyperaemia (PORH). Results In response to local heating, EMLA treatment significantly delayed the onset of vasodilatation ( p  < 0.001), time-to-peak ( p  < 0.001), time to 39 °C ( p  < 0.02), time to 42 °C ( p  < 0.006), but not time to 44 °C ( p  > 0.2). EMLA treatment also increased time-to-peak for PORH ( p  ≤ 0.01). In the experimental limb after 6 weeks, both onset time and time to peak were shorter in response to local heating at the untreated and EMLA-treated sites (all p  < 0.001). There were no changes in time-to-peak for PORH at the untreated and EMLA-treated sites ( p  ≥ 0.4); however, the peak PORH response was reduced with EMLA treatment ( p  ≤ 0.03). The 6-week intervention increased the peak PORH at the untreated sites ( p  < 0.001) but not at EMLA-treated ( p  > 0.05) sites. Comparing the control limb before and after 6 weeks, no differences in responses occurred at either the untreated skin sites ( p  ≥ 0.9) or the EMLA-treated sites ( p  ≥ 0.9). Conclusions Sensory nerve blockade attenuated the improvements in cutaneous vascular responses to thermal hyperaemia and PORH following chronic exposure to shear stress. These data demonstrate an important role for sensory nerve function in the initiation of vasodilatation to both PORH and thermal hyperaemia, in both the time to onset and the magnitude of vasodilatation. [ABSTRACT FROM AUTHOR]

This article describes the interaction between solid particles and blood propagating through a capillary. A slip condition is considered on the walls of the capillary. The rheological features of the blood are discussed by considering as a two-phase Newtonian fluid model, i.e., the suspension of cells in plasma. A perturbation method is successfully applied to obtain the series solution of the governing coupled differential equations. The series solution for both fluid and particle phase are presented up to second order approximation. The expressions for the velocity and pressure distributions under slip effects are determined within a tube. Furthermore, the current results are beneficial to understand the rheological features of blood which will be helpful to interpret and analyze more complex blood flow models. [ABSTRACT FROM AUTHOR]

Objectives Despite increasing interest in nailfold capillaroscopy, objective measures of capillary structure and blood flow have been little studied. We aimed to test the hypothesis that structural measurements, capillary flow, and a combined measure have the predictive power to separate patients with systemic sclerosis (SSc) from those with primary Raynaud's phenomenon (PRP) and healthy controls (HC). Methods 50 patients with SSc, 12 with PRP, and 50 HC were imaged using a novel capillaroscopy system that generates high-quality nailfold images and provides fully-automated measurements of capillary structure and blood flow (capillary density, mean width, maximum width, shape score, derangement and mean flow velocity). Population statistics summarise the differences between the three groups. Areas under ROC curves (A Z ) were used to measure classification accuracy when assigning individuals to SSc and HC/PRP groups. Results Statistically significant differences in group means were found between patients with SSc and both HC and patients with PRP, for all measurements, e.g. mean width (μm) ± SE: 15.0 ± 0.71, 12.7 ± 0.74 and 11.8 ± 0.23 for SSc, PRP and HC respectively. Combining the five structural measurements gave better classification (A Z  = 0.919 ± 0.026) than the best single measurement (mean width, A Z  = 0.874 ± 0.043), whilst adding flow further improved classification (A Z  = 0.930 ± 0.024). Conclusions Structural and blood flow measurements are both able to distinguish patients with SSc from those with PRP/HC. Importantly, these hold promise as clinical trial outcome measures for treatments aimed at improving finger blood flow or microvascular remodelling. [ABSTRACT FROM AUTHOR]

A numerical simulation is presented to study the heat and flow characteristics of blood flow altered by electroosmosis through the tapered micro-vessels. Blood is assumed as non-Newtonian (micropolar) nanofluids. The flow regime is considered as asymmetric diverging (tapered) microchannel for more realistic micro-vessels which is produced by choosing the peristaltic wave train on the walls to have different amplitudes and phase. The Rosseland approximation is employed to model the radiation heat transfer and temperatures of the walls are presumed constants. The mathematical formulation of the present problem is simplified under the long-wavelength, low-Reynolds number and Debye-Hückel linearization approximations. The influence of various dominant physical parameters are discussed for axial velocity, microrotation distribution, thermal temperature distribution and nanoparticle volume fraction field. However, our foremost emphasis is to determine the effects of thermal radiation and coupling number on the axial velocity and microrotation distribution beneath electroosmotic environment. This analysis places a significant observation on the thermal radiation and coupling number which plays an influential role in hearten fluid velocity. This study is encouraged by exploring the nanofluid-dynamics in peristaltic transport as symbolized by heat transport in biological flows and also in novel pharmacodynamics pumps and gastro-intestinal motility enhancement. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate conjunctival blood flow velocities and microvascular network density in patients with dry eye disease (DED). Twenty-five patients with DED and 25 healthy controls were recruited. The microvasculature and microcirculation of the temporal bulbar conjunctiva of the right eyes were assessed using a functional slit-lamp biomicroscope. Vascular variables included blood flow velocity (BFV), blood flow rate (BFR), microvascular network density and vessel diameter. A fractal analysis was performed using the box counting method to measure the fractal dimension (Dbox) representing the vessel density. The bulbar BFV was 0.59 ± 0.09 mm/s in the DED group and 0.47 ± 0.12 in the control group ( P  < 0.001). BFR was 169.5 ± 1.8 in the DED group compared to the control group (107.2 ± 49.6) (P < 0.001). Dbox was higher in DED patients (1.65 ± 0.04) than controls (1.60 ± 0.07, P  < 0.05). Moreover, the vessel diameter was larger in the DED group (21.8 ± 1.8 μm) compared with controls (17.9 ± 2.2 μm, P  < 0.001). Dbox was positively related with ocular surface disease index (OSDI) in patients with DED ( r  = 0.54, P  = 0.008). Microvascular alterations were found in the bulbar conjunctiva of DED patients, including increased blood flow velocity, higher vessel density and larger vessel diameter. [ABSTRACT FROM AUTHOR]

It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l -arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer's solution as a control site; 2) 20 mM NG-nitro- l -arginine ( l -NAME) to inhibit NO synthase activity; 3) 10 mM l -arginine to local supplement l -arginine; or 4) a combination of 5.0 mM (S)-(2‑boronoethyl)- l -cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor- l -arginine (nor-NOHA) at a rate of 2.0 μl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ± 12 vs. AA: 62 ± 6 vs. %CVCmax; P  < 0.001). This response was improved in AA at the l -arginine site (Control: 62 ± 6 vs. l -arginine: 70 ± 18%CVCmax; P  < 0.05) but not in the arginase inhibited site (Control: 62 ± 6 vs. Arginase inhibited: 62 ± 13%CVCmax; P  = 0.91). In addition, the AA group had an attenuated NO contribution to the plateau phase during 42 °C local heating relative to the CA group (CA: 56 ± 14 vs. AA: 44 ± 6 Δ %CVCmax; P  < 0.001). These findings suggest that 1) cutaneous microvascular function in response to local heating is blunted in young AA when compared to age-matched young CA; 2) this attenuated response is partly related to decrease in NO bioavailability in young AA; and 3) a local infusion of l -arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA. [ABSTRACT FROM AUTHOR]

An analytical study of microvascular non-Newtonian blood flow is conducted incorporating the electro-osmosis phenomenon. Blood is considered as a Bingham rheological aqueous ionic solution. An externally applied static axial electrical field is imposed on the system. The Poisson-Boltzmann equation for electrical potential distribution is implemented to accommodate the electrical double layer in the microvascular regime. With long wavelength, lubrication and Debye-Hückel approximations, the boundary value problem is rendered non-dimensional. Analytical solutions are derived for the axial velocity, volumetric flow rate, pressure gradient, volumetric flow rate, averaged volumetric flow rate along one time period, pressure rise along one wavelength and stream function. A plug swidth is featured in the solutions. Via symbolic software (Mathematica), graphical plots are generated for the influence of Bingham plug flow width parameter, electrical Debye length and Helmholtz-Smoluchowski velocity (maximum electro-osmotic velocity) on the key hydrodynamic variables. This study reveals that blood flow rate accelerates with decreasing the plug width (i.e. viscoplastic nature of fluids) and also with increasing the Debye length parameter. [ABSTRACT FROM AUTHOR]

In most of the medical therapies, electromagnetic field plays important role to modulate the blood flow and to reduce the pain of human body. With this fact, this paper presents a mathematical model to study the peristaltic blood flow through porous microvessels in the presence of electrohydrodynamics. The effects of Joule heating and different zeta potential are also considered. Darcy law is employed for porous medium. The mathematical analysis is carried out in the form of electroosmosis, flow analysis and heat transfer analysis. Velocity slip conditions are imposed to solve momentum equation and thermal energy equation. Time dependent volumetric flow rate is considered which varies exponentially. Closed form solutions for potential function is obtained under Debye-H ü ckel approximation and velocity and temperature fields are obtained under low Reynolds number and large wavelength approximations. The influence of Hartmann number, electroosmotic parameter, slip parameters, Zeta potential, and couple stress parameter on flow characteristics, pumping characteristics and trapping phenomenon is computed. The effects of thermal slip parameters, Joule heating parameter, and Brinkman number on heat transfer characteristics are also presented graphically. Finally, the effect of Brinkman number on a graph between Nusselt number and Joule heating parameter is examined. [ABSTRACT FROM AUTHOR]

Objectives To explore the feasibility of a new quantitative method for microvascular function: non-invasive retinal function imaging (RFI). in sickle cell disease (SCD) patients and healthy controls and have it benchmarked against Laser Speckle Contrast Imaging (LSCI) measurements. Methods The variability of Microvascular measurements was assessed in 8 SCD patients and 8 healthy matched controls. Measurements were conducted twice on two different study days. RFI was performed for assessment of arterial and venous retinal blood flow. LSCI measurements included post occlusive reactive hyperemia and IBH challenges. Measured variables included basal flow, flow upon occlusion-reperfusion and flow during an IBH. Results RFI arterial flow and venous flow and LSCI basal flow and peak flow showed excellent intra subject repeatability between days (CVC of 8.5% 9.5%, 7.6% and 7.7% respectively) and between measurements on one day (CVC of 7.0%, 7.7%, 7.6% and 4.7% respectively). RFI arterial flow ( p < 0.002), and RFI venous flow ( p = 0.007) differed significantly between SCD patients and controls in as did LSCI basal flow, maximal flow and delta flow during IBH ( p < 0.0001). Conclusions RFI showed low variability for all readout measures, comparable with most microvascular measures from LSCI. The discriminating power of the RFI between SCD patients and controls demonstrate the feasibility of this device for quantitative assessment of the microcirculation in clinical research. [ABSTRACT FROM AUTHOR]

Objective To study blood flow, vascular volume and arterio-venous passages in induced mammary tumours of the rat to characterize parameters possibly responsible for tumour hyponutrition. Method Dimethylbenzanthracene-induced mammary tumours in Sprague-Dawley rats were studied. Regional blood flow was studied by use of the radioactive microsphere tracer technique using 141 Cerium-labelled 15 μm spheres coinjected into the left cardiac ventricle with 125 Iodine-labelled 25 μm spheres. Blood volume was studied by use of 125 Iodine- or 99m Technetium-labelled human serum albumin, the latter allowing autoradiography of tumour sections for visualization of flow and volume. Results Twenty-seven rats with 170 tumours had a mean tumour blood flow of 48 and 67 mL × min − 1 × 100 g − 1 using 15 and 25 μm sphere data, respectively, indicating a significant passage through vessels between 15 and 25 μm. The lungs showed a “nominal bronchial” blood flow of 260 and 135 mL × min − 1 × 100 g − 1 for the 15 and 25 μm spheres, respectively, indicating pulmonary trapping, particularly of small spheres passing the systemic circulation in vessels larger than 15 μm. There was a positive correlation between the total tumour blood flow within individual rats and trapped spheres of both dimensions in the lungs, indicating shunts also larger than 25 μm. Normal tissues disclosed only small differences in regional blood flow as measured by the two spheres. Blood volume was studied in 20 rats with 120 tumours, with a vascular volume of 3.6 mL × 100 g − 1 representing a blood turnover > 15 times/min. Blood volume co-localized with perfusion as seen in autoradiographs. Conclusion In induced rat mammary tumours, a high fraction of blood, 28%, passes arterio-venous vessels between 15 and 25 μm and there also exist passages > 25 μm. These findings indicate that the functional capacity of the tumour vascular bed might be impaired, adding to the abnormal microenvironment of tumours. [ABSTRACT FROM AUTHOR]

Background A single insulin injection was shown to improve microcirculatory blood flow. Our aim was to examine the effects of 4 weeks of insulin therapy by three randomly assigned insulin analog regimens (Detemir, Aspart, and their combination) on cutaneous blood flow (CBF) and microcirculatory endothelial function as an add-on to metformin in type 2 diabetic patients poorly controlled on oral antidiabetic treatment. Methods Fourty-two type 2 diabetic patients with no history of cardiovascular disease in secondary failure to oral antidiabetic agents had CBF measurements before and after acetylcholine (Ach) iontophoretic administration. CBF measurements were performed at fasting and after a standardized breakfast during the post-prandial period. Before randomization (Visit 1, V1) during the tests, participants took only metformin. The same tests were repeated after 4 weeks of insulin treatment (Visit 2, V2). Results Thirty-four patients had good quality recordings for both visits. During V1, CBF and CBF response to Ach increased in the post-prandial period. After 4 weeks of insulin treatment, metabolic parameters improved. Compared to V1, CBF at fasting did not increase at V2 but there was an improvement in endothelial function at fasting after Ach iontophoresis, without difference across insulin regimens. Oxidative stress markers were not modified, and E -selectin and vascular cell adhesion molecule 1 levels decreased after insulin treatment, without differences between insulin groups. Conclusions A strategy of improving glycemic control for 4 weeks with insulin analogs improves microcirculatory endothelial reactivity and reduces endothelial biomarkers at fasting, whatever the insulin regimen used. Insulin therapy associated to metformin is able to improve fasting microvascular endothelial function even before complete metabolic control. [ABSTRACT FROM AUTHOR]

Nanoparticle-based drug targeting is an important platform for the treatment of cardiovascular disorders. Magnetic drug targeting is more significant as it is a noninvasive procedure and biocompatible. The present problem aims to understand magnetic drug delivery to a specific location in a permeable blood vessel under the vibration and magnetic environment. Caputo fractional-order time derivatives are used in the governing equations. The momentum equations are solved analytically and presented in the form of Lorenzo-Hartley and Robotonov-Hartley functions and convolution of the Laplace transform. Convolution integrations are solved by using the numerical integration technique. The Fourth order Runge-Kutta method (RK4) is used to solve the force balance equation. The influence of pertinent parameters such as Reynolds number, pulsatile frequency, magnetic field strength, Darcy number and fractional-order parameters are presented through graphs. It is observed that increasing Reynolds number results in decreasing the tendency of the drug to capture near the tumor site, whereas the pulsatile frequency presents an opposite phenomenon. Increasing the magnetic field strength and Darcy number boosts the capture efficiency of drug particles near the tumor site. The short memory effect efficiently captures the magnetic drug carriers to a specific location under the action of suitable magnetic field strength. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of laser speckle contrast imaging (LSCI) for monitoring urethral blood flow (UBF). In this study, 18 healthy, virgin female Sprague–Dawley rats aged 8-week-old were used. The animals were divided into the sham group (n = 9) and the vaginal distension (VD) group (n = 9). The sham group underwent one catheterization of the vagina without distension and the VD group underwent one VD. Following the VD or sham treatment for one week, LSCI assessment of urethral blood flow was performed during bladder filling and leak point pressure (LPP) process. During the LPP process, in the VD group, the mean LPP was significantly lower than in the sham group (p < 0.05) and the mean UBF level was also significantly lower than in the sham group (p < 0.05) in the LPP condition. The mean relative change of UBF (Δ Flow) was significantly different between the sham group and VD group. The value was 0.646 ± 0.229 and 0.295 ± 0.19, respectively (p < 0.05). During the bladder filling process, the VD group had a significant lower mean UBF level than the sham group under full bladder conditions (p = 0.008). The mean ΔFlow was also significantly lower than in the sham group. The value was 0.115 ± 0.121 and 0.375 ± 0.127, respectively (p = 0.016). The results confirmed that LSCI was able to determine UBF in female rats. The VD group had lower baseline UBF and lower increases in UBF during bladder filling and LPP process compared with the sham group. [ABSTRACT FROM AUTHOR]

To determine age-related alterations in the retinal capillary function (RCF, the ability to transport blood flow) in healthy subjects. A total of 148 healthy subjects (aged 18 to 83 years) were enrolled, and one eye of each subject was imaged. Retinal blood flow (RBF) was measured using a Retinal Function Imager, and retinal capillary density (RCD, expressed as fractal dimension Dbox) was measured using optical coherence tomography angiography. RCF was defined as the ratio of RBF to RCD, representing the ability to transport blood flow. The relationship between RCF and age was analyzed. In addition, the cohort was divided into four groups (G1, <35 years, G2, 35–49 years, G3, 50–64 years, and G4, ≥65 years) for further analysis. With all data, the relation between the RCF and age had a trend of a quadratic model (G1–4: r = 0.16, P = 0.14). After 35 years (i.e., G2–4), the relation had a trend between the RCF and age fitted into a negative linear model (r = −0.23, P = 0.05). Moreover, after 50 years (i.e., G3–4), the negative linear model became stronger (r = −0.37, P = 0.03). The average RCF was 2.24 ± 0.22 μl/s/Dbox in G4, significantly lower than that in G2 (2.65 ± 0.56 μl/s/Dbox, P = 0.018) and G3 (2.64 ± 0.70 μl/s/Dbox, P = 0.034), but did not reach a significant level compared to that in G1 (2.55 + 0.51 μl/s/Dbox, P = 0.056). This is the first study to determine age-related alterations in the RCF in a healthy population. Decreased RCF in the older group may represent a characteristic pattern of normal aging. • Age-related alterations of retinal capillary function in a healthy population • Retinal functional imager used to measure blood flow velocities • Significantly lower retinal capillary function in older age groups [ABSTRACT FROM AUTHOR]

Objective This study compares the effectiveness of a neuromuscular electrical stimulation (NMES) device and an intermittent pneumatic compression (IPC) device on enhancing microcirculatory blood flow in the thigh of healthy individuals, when stimulation is carried out peripherally at the calf. Materials and methods Blood microcirculation of ten healthy individuals was recorded using laser speckle contrast imaging (LSCI) technique. A region of interest (ROI) was marked on each participant thigh. The mean flux within the ROI was calculated at four states: rest, NMES device with visible muscle actuation (VMA), NMES device with no visible muscle actuation (NVMA) and IPC device. Results Both NMES and IPC devices increased blood flow in the thigh when stimulation was carried out peripherally at the calf. The NMES device increased mean blood perfusion from baseline by 399.8% at the VMA state and 150.6% at the NVMA state, IPC device increased the mean blood perfusion by 117.3% from baseline. Conclusion The NMES device at VMA state increased microcirculation by more than a factor of 3 in contrast to the IPC device. Even at the NVMA state, the NMES device increased blood flow by 23% more than the IPC device. Given the association between increased microcirculation and reduced oedema, NMES may be a more effective modality than IPC at reducing oedema, therefore further research is needed to explore this. [ABSTRACT FROM AUTHOR]

In this study, three-dimensional (3D) blood flow of the feto-placental vasculature system of the mouse placenta was investigated using computational fluid dynamics (CFD) methods and finite element analysis. Micro-computerized tomography (micro-CT) images were used to acquire the 3D geometry of the feto-placental vasculature system, and image-processing software has been used to calculate the 3D morphology of the placenta. The flow was analyzed numerically and compared to the experimental data received from the same model. The numerical and experimental results agree well. Experimentally measured time dependent blood velocity data, available in the literature, was used as the inlet boundary condition to represent the fetal blood pulsatile flow. Velocity profiles and pressure distributions are investigated during different phases of the unsteady flow. The results clearly illustrate the important role of the vasculature structure (e.g., diameter and curvature) in the fetal hemodynamics, which to our knowledge has not been examined previously. The data also show that, at each bifurcation, the blood flow velocity decreases significantly in the transition from the parent vessel (i.e., umbilical artery) to the daughter vessels because of the higher total cross-sectional area of the daughter vessels compared to the parent vessel. It can also be observed that pressure drop at the umbilical artery and pressure drop across the arterial trees obtained in this study agree well with the physiological data reported in the literature. Moreover, the velocity profiles after each bifurcation are symmetric. Finally, from the results no secondary flow has been observed in the vasculature system. This study provides a foundation in understanding and modeling the complex structure of the feto-placental vasculature system and serves as a first step towards developing new concepts for computational analysis of the feto-placental vasculature systems of both human and mouse to better understand how the placenta functions and how gas and nutrient exchange between the mother and fetus. [ABSTRACT FROM AUTHOR]

Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation. The skin of healthy subjects' hand dorsum ( n = 8) was heated to 42 °C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03 °C/s, 0.02 °C/s and 0.01 °C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively. The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03 °C/s and 0.02 °C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01 °C/s) (p-value < 0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01 °C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact. [ABSTRACT FROM AUTHOR]

Previous work has demonstrated that spectral analysis is a useful tool to non-invasively ascertain the mechanisms of control of the cutaneous circulation. The majority of work using spectral analysis has focused on local control mechanisms, with none examining reflex control. Skin blood flow was analysed using spectral analysis on the dorsal aspect of the forearm of 7 males and 7 females during passive heat stress, with mean forearm and local temperature at the site of measurement maintained at thermoneutral (33 °C) to minimize the effect of local control mechanisms. Participants were passively heated to ~ 1.2 ± 0.1 °C above baseline rectal temperature ( d = 4.0, P < 0.001) using a water-perfused, tube lined suit, with skin blood flow assessed using a laser-Doppler probe with an integrated temperature monitor. Spectral analysis was performed using a Morlet wavelet on the entire data set, with median power extracted during 20 min of data during baseline (normothermia) and hyperthermia. Passive heat stress significantly increased laser-Doppler flux above baseline ( d = 4.7, P < 0.001). Spectral power of the endothelial nitric oxide-independent (0.005–0.01 Hz; d = 1.1, P = 0.004), neurogenic (0.2–0.05 Hz; d = 0.6, P = 0.025), myogenic (0.05–0.15 Hz; d = 1.5, P = 0.002), respiratory (0.15–0.4 Hz; d = 1.4 P = 0.002), and cardiac (0.4–2.0 Hz; d = 1.1, P = 0.012) frequency intervals increased with passive heat stress. In contrast, the endothelial nitric oxide-dependent frequency interval did not change (0.01–0.02 Hz; d = 0.3, P = 0.09) with passive heat stress. These data suggest that cutaneous reflex vasodilatation is neurogenic in origin and not mediated by endothelial-nitric oxide synthase, and are congruent with invasive examinations of reflex cutaneous vasodilatation. [ABSTRACT FROM AUTHOR]

In this article, simultaneous effects of coagulation (blood clot) and variable magnetic field on peristaltically induced motion of non-Newtonian Jeffrey nanofluid containing gyrotactic microorganism through an annulus have been studied. The effects of an endoscope also taken into consideration in our study as a special case. The governing flow problem is simplified by taking the approximation of long wavelength and creeping flow regime. The resulting highly coupled differential equations are solved analytically with the help of perturbation method and series solution have been presented up to second order approximation. The impact of all the sundry parameters is discussed for velocity profile, temperature profile, nanoparticle concentration profile, motile microorganism density profile, pressure rise and friction forces. Moreover, numerical integration is also used to evaluate the expressions for pressure rise and friction forces for outer tube and inner tube. It is found that velocity of a fluid diminishes near the walls due to the increment in the height of clot. However, the influence of magnetic field depicts opposite behavior near the walls. [ABSTRACT FROM AUTHOR]

Menthol is a vasoactive compound that is widely used in topical analgesic agents. Menthol induces cutaneous vasodilation, however the underlying mechanisms are unknown. Determining the rates of appearance and clearance of menthol in the skin is important for optimizing topical treatment formulation and dosing. The purpose of this study was to determine the mechanisms contributing to menthol-mediated cutaneous vasodilation and to establish a time course for menthol appearance/clearance in the skin. Ten young (23 ± 1 years, 5 males 5 females) subjects participated in two protocols. In study 1, four intradermal microdialysis fibers were perfused with increasing doses of menthol (0.1–500 mM) and inhibitors for nitric oxide (NO), endothelium derived hyperpolarizing factors (EDHFs), and sensory nerves. Skin blood flow was measured with laser Doppler flowmetry and normalized to %CVC max . In study 2, two intradermal microdialysis fibers were perfused with lactated Ringer's solution. 0.017 mL·cm − 2 of a 4% menthol gel was placed over each fiber. 5 μL samples of dialysate from the microdialysis fibers were collected every 30 min and analyzed for the presence of menthol with high performance gas chromatography/mass spectrometry. Skin blood flow (laser speckle contrast imaging) and subjective ratings of menthol sensation were simultaneously obtained with dialysate samples. In study 1, menthol induced cutaneous vasodilation at all doses ≥ 100 mM (all p < 0.05). However, inhibition of either NO, EDHFs, or sensory nerves fully inhibited menthol-mediated vasodilation (all p > 0.05). In study 2, significant menthol was detected in dialysate 30 min post menthol application (0.89 ng, p = 0.0002). Relative to baseline, cutaneous vasodilation was elevated from minutes 15–45 and ratings of menthol sensation were elevated from minute 5–60 post menthol application (all p < 0.05). Menthol induces cutaneous vasodilation in the skin through multiple vasodilator pathways, including NO, EDHF, and sensory nerves. Topical menthol is detectable in the skin within 30 min and is cleared by 60 min. Skin blood flow and perceptual measures follow a similar time course as menthol appearance/clearance. [ABSTRACT FROM AUTHOR]

Objective Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. This study was designed to monitor and characterize the hepatic microcirculatory perfusion following different volumes of hepatectomy in rats by using laser speckle contrast image (LSCI) and Oxygen to See (O2C), a spectrometric device. Methods The microcirculatory liver blood flow of the rats that underwent 68%, 85% and 90% hepatectomy (68PH, 85PH and 90PH) was monitored with LSCI and O2C before and following the hepatectomy. The portal venous flow (PVF) and hepatic arterial flow (HAF) were measured with an ultrasonic flowmeter. Liver regeneration, liver injury, histologic evaluation and gene expression were also assessed at 12 h, 24 h, 3 d and 7 d post hepatectomy. Results All the 68PH and 85PH rats survived, and 57% of the 90PH rats survived. After hepatectomy, both PVF and HAF decreased transiently, with the PVF of the 85PH and 90PH rats significantly lower than that of the 68PH rats. In contrast, the PVF and HAF per gram of liver weight were greatly increased after liver resection and were proportional to the volume of resected liver. Correspondingly, the microcirculatory liver blood flow of the 68PH, 85PH and 90PH rats, as assessed by both LSCI and O2C, were increased after hepatectomy, and the 90PH group was significantly higher than the 68PH and 85PH groups. The hyperperfusion continued for approximately 3 days and returned to baseline following the completion of liver regeneration. The liver venous oxygen saturation of the three groups decreased immediately after hepatectomy and returned to baseline from 24 h after hepatectomy. The 90PH rats also showed delayed liver regeneration and the most severe liver injury, as reflected by increased serum ALT, AST and TBIL levels, hepatocellular vacuolization, and inflammatory and endothelial constriction gene expressions (TNF-α, IL-1β, MIP-1α, ET-1 and TM-1). Conclusion Hepatic microcirculation hyperperfusion resulting from major and extended liver resection could be assessed by LSCI and O2C methods. The 90PH in rats led to extraordinary sinusoidal hyperperfusion, severe endothelial injury and liver failure. Monitoring the changes of hepatic microcirculation perfusion following extended hepatectomy or small-for-size liver transplantation may help to analyze the extent of hyperperfusion. [ABSTRACT FROM AUTHOR]

Cerebrovascular diseases continue to be one of the leading causes of morbidity and mortality in humans. Abnormalities in dynamic cerebral autoregulation (dCA) have been implicated in many of these disease conditions. Accurate models are therefore needed to better understand the complex pathophysiology behind impaired dCA. We thus present here a simple framework for modelling a vessel-driven network model of dCA in the microvasculature, as opposed to the conventional compartmental modelling approach. Network models incorporate the actual connectivity and anatomy of the vasculature, thereby allowing us to include and trace changes in the calibre and morphology of individual vessels, investigate the spatial specificity and heterogeneity of the various control mechanisms to help disentangle their contributions, and link the model parameters to the actual network physiology. The proposed control feedback mechanisms are incorporated at the level of the individual vessel, and the dynamic pressure and flow fields are solved for here within a simple vessel network. In response to an upstream pressure drop, the network is found to be able to recover cerebral blood flow (CBF) while exhibiting the characteristic autoregulatory behaviour in terms of changes in vessel calibre and the biphasic flow response. We assess the feasibility of our formulation in larger networks by comparing the simulation results to those obtained using a one-dimensional (1D) model of CBF applied to the same microvasculature network and find that our model results are in very good agreement with the 1D solution, while significantly reducing the computational cost, thus enabling more detailed models of network behaviour to be adopted in the future. Accurate and computationally feasible models of dCA that are more representative of the vasculature can help increase the translatability of haemodynamic models into the clinical environment, which would help develop more informed treatment guidelines for patients with cerebrovascular diseases. • Present a novel approach for modelling autoregulation in the brain microvasculature • Dynamic behaviour due to the fluid-wall interactions affects blood flow. • Different vessel generations respond differently to blood pressure disturbances. [ABSTRACT FROM AUTHOR]

Subclinical damage to both the small and large vessels may contribute to the development and progression of cardiovascular disease. Scanning laser Doppler flowmetry (SLDF), an established method used to measure retinal microcirculation, has been successfully applied in hypertensive and post-stroke patients. Retinal microcirculation was assessed in 158 patients with type 1 diabetes and 38 age-matched healthy controls. The diabetics were divided into 3 groups: group A with diabetes duration <12 months, group B with diabetes with 1–10 years, and group C >10 years of diabetes. Retinal capillary structure and perfusion were evaluated using a Heidelberg retina flowmeter and automatically analyzed with full-field perfusion imaging. Age and BMI were comparable in all the diabetic patients and the controls (mean age 24.8 ± 4.7 years, mean BMI 22.9 ± 4.1). In the univariate analyses, RCF (retinal capillary flow) was significantly higher in group A (297 ± 121 arbitrary units [AU]) vs group B (236 ± 52 AU; p = 0.007) and group C (236 ± 70 AU; p = 0.008) and comparable to that of the controls (p = 0.46). Additionally, the WLR (Wall-to-Lumen Ratio) was highest in group C compared to the other diabetic subgroups and controls (p = 0.001). Multivariate regression analyses including age, BMI, sex, HbA1c, smoking, systolic blood pressure, and diabetes duration as covariates, showed, that only diabetes duration was significantly associated with WLR variations, whereas HbA1c was significantly linked to retinal capillary flow levels. New-onset diabetes is associated with an increase in RCF, which then gradually decreased with the duration of the disease. Structural changes of the retinal arterioles estimated via WLR are evident later in the course of diabetes, especially when the disease duration exceeded 10 years. [Display omitted] • New-onset of diabetes is associated with an increase in RCF. • RCF decreases with the duration of diabetes. • Structural changes of the retinal arterioles estimated via WLR are evident after >10 years of disease's duration. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction (CMD) is a cause of ischaemia with non-obstructive coronary arteries (INOCA). It is notoriously underdiagnosed due to the need for invasive microvascular function testing. We hypothesized that systemic microvascular dysfunction could be demonstrated non-invasively in the microcirculation of the bulbar conjunctiva in patients with CMD. Patients undergoing coronary angiography for the investigation of chest pain or dyspnoea, with physiologically insignificant epicardial disease (fractional flow reserve ≥0.80) were recruited. All patients underwent invasive coronary microvascular function testing. We compared a cohort of patients with evidence of CMD (IMR ≥25 or CFR <2.0); to a group of controls (IMR <25 and CFR ≥2.0). Conjunctival imaging was performed using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allows measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. A total of 111 patients were included (43 CMD and 68 controls). There were no differences in baseline demographics, co-morbidities or epicardial coronary disease severity. The mean number of vessel segments analysed per patient was 21.0 ± 12.8 (3.2 ± 3.5 arterioles and 14.8 ± 10.8 venules). In the CMD cohort, significant reductions were observed in axial/cross-sectional velocity, blood flow, wall shear rate and stress. The changes in microvascular function linked to CMD can be observed non-invasively in the bulbar conjunctiva. Conjunctival vascular imaging may have utility as a non-invasive tool to both diagnose CMD and augment conventional cardiovascular risk assessment. [Display omitted] • Coronary microvascular dysfunction is prevalent and associated with an adverse cardiovascular prognosis. • This is the first study to demonstrate alterations in systemic microvascular function in patients with coronary microvascular disease. • Demonstration of microvascular disease may have utility in cardiovascular risk assessment. [ABSTRACT FROM AUTHOR]

• Flowmotion imaging displays significant spatiotemporal variations in forearm skin blood flow. • Flowmotion imaging has potential to be more accurate than single-point techniques. • A simple and effective method for motion artifact removal is presented. [ABSTRACT FROM AUTHOR]

Little is known about the acute changes in cutaneous microvascular function that occur in response to exercise, the accumulation of which may provide the basis for beneficial chronic cutaneous vascular adaptations. Therefore, we examined the effects of acute exercise on cutaneous thermal hyperaemia. Twelve healthy, recreationally active participants (11 male, 1 female) performed 30-minute cycling at 50 % (low-intensity exercise, LOW) or 75 % (high-intensity exercise, HIGH) maximum heart rate. Laser Doppler flowmetry (LDF) and rapid local skin heating were used to quantify cutaneous thermal hyperaemia before (PRE), immediately following (IMM) and 1-h (1HR) after exercise. Baseline, axon reflex peak, axon reflex nadir, plateau, maximum skin blood flow responses to rapid local heating (42 °C for 30-min followed by 44 °C for 15-min) at each stage were assessed and indexed as cutaneous vascular conductance [CVC = flux / mean arterial blood pressure (MAP), PU·mm Hg−1], and expressed as a percentage of maximum (%CVC max). Exercise increased heart rate (HR), MAP and skin blood flow (all P < 0.001), and to a greater extent during HIGH (all P < 0.001). The axon reflex peak and nadir were increased immediately and 1-h after exercise (all comparisons P < 0.01 vs. PRE), which did not differ between intensities (peak: P = 0.34, axon reflex nadir: P = 0.91). The endothelium-dependent plateau response was slightly elevated after exercise (P = 0.06), with no effect of intensity (P = 0.58) nor any interaction effect (P = 0.55). CONCLUSION: Exercise increases cutaneous microvascular axonal responses to local heating for up to 1-h, suggesting an augmented sensory afferent function post-exercise. Acute exercise may only modestly affect endothelial function in cutaneous microcirculation. • The changes in skin microvascular function that might occur after exercise are unclear. • Rapid local skin heating was used to quantify cutaneous microvascular function. • The axon reflex peak and nadir were increased after exercise independent of intensity. • The endothelium-dependent plateau was elevated after exercise independent of intensity. • Exercise augments cutaneous sensory afferent and endothelial function. [ABSTRACT FROM AUTHOR]

Young non-Hispanic black (BL) males have displayed lower blood flow (BF) and vascular conductance (VC), but intact functional sympatholysis, during upper limb exercise when compared to non-Hispanic white (WH) males. This study sought to explore if similar differences were also present in the lower limbs. Thirteen young BL males and thirteen WH males completed one visit comprised of rhythmic lower limb (plantar flexion) exercise as well as upper limb (handgrip) exercise for a limb-specific comparison. Limb BF, mean arterial pressure (MAP), and VC were evaluated at three submaximal workloads (8, 16, and 24 kg). To determine potential limb differences in functional sympatholysis, the impact of sympathetic nervous system activation (via cold-pressor test (CPT)) was evaluated at rest and during steady state exercise (30 % of maximal voluntary contraction) on a subsequent visit. MAP responses to lower and upper limb exercise were elevated in young BL males (vs WH males), resulting in significantly lower VC responses in the upper limb, but not the lower limb. Further, BL males, when compared to WH males, revealed no differences in functional sympatholysis, evident by similar responses in both the exercising leg and arm VC during CPT. The findings of the current study indicate that although elevated MAP responses were observed during both lower and upper limb exercise in young BL males, vascular conductance was only hindered in the upper limbs. This may potentially highlight enhanced compensatory mechanisms in the lower limb (vs upper limb) to maintain perfusion in young BL males. • Black males exhibited greater pressor responses to lower and upper limb exercise. • Vascular conductance was lower in the upper limbs only (vs lower limbs). • Blood flow responses were better maintained in the lower limbs (vs upper limbs). • Functional sympatholysis was not impaired in either the upper or lower limbs. [ABSTRACT FROM AUTHOR]

Since blood viscosity is a basic parameter for understanding hemodynamics in human physiology, great amount of research has been done in order to accurately predict this highly non-Newtonian flow property. However, previous works lacked in consideration of hemodynamic changes induced by heterogeneous vessel networks. In this paper, the effect of bifurcation on hemodynamics in a microvasculature is quantitatively predicted. The flow resistance in a single bifurcation microvessel was calculated by combining a new simple mathematical model with 3-dimensional flow simulation for varying bifurcation angles under physiological flow conditions. Interestingly, the results indicate that flow resistance induced by vessel bifurcation holds a constant value of approximately 0.44 over the whole single bifurcation model below diameter of 60 μm regardless of geometric parameters including bifurcation angle. Flow solutions computed from this new model showed substantial decrement in flow velocity relative to other mathematical models, which do not include vessel bifurcation effects, while pressure remained the same. Furthermore, when applying the bifurcation angle effect to the entire microvascular network, the simulation results gave better agreements with recent in vivo experimental measurements. This finding suggests a new paradigm in microvascular blood flow properties, that vessel bifurcation itself, regardless of its angle, holds considerable influence on blood viscosity, and this phenomenon will help to develop new predictive tools in microvascular research. [ABSTRACT FROM AUTHOR]

Objectives Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools. Methods 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images. Results The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs = 0.494; 95% CI [0.357, 0.615]; p < 0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r = 0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. Conclusion This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin. [ABSTRACT FROM AUTHOR]

In this paper, an adaptive model for tumor induced angiogenesis is developed that integrates generation and diffusion of a growth factor originated from hypoxic cells, adaptive sprouting from a parent vessel, blood flow and structural adaptation. The proposed adaptive sprout spacing model (ASS) determines position, time and number of sprouts which are activated from a parent vessel and also the developed vascular network is modified by a novel sprout branching prediction algorithm. This algorithm couples local vascular endothelial growth factor (VEGF) concentrations, stresses due to the blood flow and stochastic branching to the structural reactions of each vessel segment in response to mechanical and biochemical stimuli. The results provide predictions for the time-dependent development of the network structure, including the position and diameters of each segment and the resulting distributions of blood flow and VEGF. Considering time delays between sprout progressions and number of sprouts activated at different time durations provides information about micro-vessel density in the network. Resulting insights could be useful for motivating experimental investigations of vascular pattern in tumor induced angiogenesis and development of therapies targeting angiogenesis. [ABSTRACT FROM AUTHOR]

Menthol, the active ingredient in several topically applied analgesics, activates transient receptor potential melastatin 8 (TRPM8) receptors on sensory nerves and on the vasculature inducing a cooling sensation on the skin. Ilex paraguariensis is also a common ingredient in topical analgesics that has potential vasoactive properties and may alter the mechanisms of action of menthol. We sought to characterize the microvascular effects of topical menthol and ilex application and to determine the mechanism(s) through which these compounds may independently and combined alter cutaneous blood flow. We hypothesized that menthol would induce vasoconstriction and that ilex would not alter skin blood flow (SkBF). Three separate protocols were conducted to examine menthol and ilex-mediated changes in SkBF. In protocol 1, placebo, 4% menthol, 0.7% ilex, and combination menthol + ilex gels were applied separately to the skin and red cell flux was continuously measured utilizing laser speckle contrast imaging (LSCI). In protocol 2, seven concentrations of menthol gel (0.04%, 0.4%, 1%, 2%, 4%, 7%, 8%) were applied to the skin to model the dose–response curve. In protocol 3, placebo, menthol, ilex, and menthol + ilex gels were applied to skin under local thermal control (34 °C) both with and without sensory nerve blockage (topical lidocaine 4%). Post-occlusive reactive hyperemia (PORH) and local heating (42 °C) protocols were conducted to determine the relative contribution of endothelium derived hyperpolarizing factors (EDHFs)/sensory nerves and nitric oxide (NO), respectively. Red cell flux was normalized to mean arterial pressure expressed as cutaneous vascular conductance (CVC: flux·mm Hg − 1 ) in all protocols. Topical menthol application increased SkBF compared to placebo (3.41 ± 0.33 vs 1.1 ± 0.19 CVC: p < 0.001). During the dose–response, SkBF increased with increasing doses of menthol (main effect, p < 0.05) with an ED 50 of 1.0%. Similarly, SkBF was increased after menthol application during PORH (3.62 ± 0.29 vs. 2.50 ± 0.21 flux·mm Hg − 1 ; p < 0.001), but not local heating (2.98 ± 0.24 vs 2.86 ± 0.32 flux·mm Hg − 1 ; p = 0.44). Concurrent sensory nerve inhibition attenuated menthol-mediated vasodilation at thermoneutral baseline (1.29 ± 0.19 flux·mm Hg − 1 ; p < 0.001) and during PORH (2.79 ± 0.28 flux·mm Hg − 1 ; p < 0.001), but not during local heating (3.45 ± 0.21 flux·mm Hg − 1 ; p = 0.1). Topically applied menthol, but not ilex, dose-dependently increases blood flow in the cutaneous microvasculature. This increase in blood flow is mediated, in-part by sensory nerves and EDHFs. [ABSTRACT FROM AUTHOR]

Laser speckle contrast imaging (LSCI) provides a noninvasive and cost effective solution for in vivo monitoring of blood flow. So far, most of the researches consider changes in speckle pattern ( i.e. correlation time of speckle intensity fluctuation), account for relative change in blood flow during abnormal conditions. This paper introduces an application of LSCI for monitoring wound progression and characterization of cutaneous wound regions on mice model. Speckle images are captured on a tumor wound region at mice leg in periodic interval. Initially, raw speckle images are converted to their corresponding contrast images. Functional characterization begins with first segmenting the affected area using k -means clustering, taking wavelet energies in a local region as feature set. In the next stage, different regions in wound bed are clustered based on progressive and non-progressive nature of tissue properties. Changes in contrast due to heterogeneity in tissue structure and functionality are modeled using LSCI speckle statistics. Final characterization is achieved through supervised learning of these speckle statistics using support vector machine. On cross evaluation with mice model experiment, the proposed approach classifies the progressive and non-progressive wound regions with an average sensitivity of 96.18%, 97.62% and average specificity of 97.24%, 96.42% respectively. The clinical information yield with this approach is validated with the conventional immunohistochemistry result of wound to justify the ability of LSCI for in vivo , noninvasive and periodic assessment of wounds. [ABSTRACT FROM AUTHOR]

The constant inflow and variable outflow (CIVO) theory correctly predicts that spontaneous pulsation of the retinal veins will be visible close to the point where the vein exits the eye at the lamina cribrosa but will decrease rapidly in amplitude and become too small to see only a short distance upstream. However, the phase of vein oscillation relative to the oscillation of the intraocular pressure (IOP) predicted by CIVO has been unclear and controversial. We show that the CIVO model is indeterminate in predicting such phase relations. We propose a simple extension of the CIVO model that retains its basic equations but applies them to a larger domain that includes not only the intraocular (pre-laminar) portion of the vein but also the retrobulbar (post-laminar) portion of the vein behind the eye. We show that this extended CIVO model makes definite predictions about the phase of vein oscillation relative to the oscillation of IOP. This phase relationship is determined by the relative amplitude and phase of pulsations of the IOP and of the cerebrospinal fluid pressure (CSFP). If IOP and CSFP oscillate in phase, then the pre-laminar vein oscillates in phase with IOP when the amplitude of CSFP exceeds the amplitude of IOP but oscillates in counter phase with IOP when the amplitude of IOP exceeds that of CSFP. These relationships are modified when there is a phase difference between the oscillations of IOP and CSFP. When CSFP leads IOP, the phase of vein oscillation is advanced if the amplitude of CSFP exceeds that of IOP and is delayed if the amplitude of IOP exceeds that of CSFP. The result in each case is that maximum vein size occurs during the rising phase of IOP (ocular systole). We conclude that the driving force of vein oscillation is the difference between the oscillations of IOP and CSFP. The phase of this difference determines the phase relationships above. We show that additional delays in the phase of venous pulsation relative to that of IOP are induced by constriction of the vein within the lamina cribrosa and by recording the vein pulsations upstream from the lamina cribrosa. The amplitude of vein oscillation is proportional to the amplitude of the driving force and to the venous capacitance. Loss of spontaneous retinal vein pulsation with increase in mean CSFP is determined primarily by reduced venous capacitance. Increased amplitude of pulsation may occur when IOP is increased. It is the result of increased venous capacitance and possibly increased driving force of the pulsation. However, in chronic glaucoma the increase in capacitance may be counteracted by venous outflow obstruction, and the increase in driving force may be counteracted by reduced ocular blood flow. As a result retinal vein oscillation may be reduced in amplitude. [ABSTRACT FROM AUTHOR]

Intense pulsed light (IPL) with low energy insufficient to completely destroy a vasculature was applied to rabbit ears to investigate vasculature alteration. Glycerol was combined with IPL to enhance the transfer efficacy of IPL energy. Both trans-illumination and laser speckle contrast images were obtained and analyzed after treatment. The application of IPL and glycerol combination induced vasodilation and improvement in blood flow. Moreover, such phenomenon was maintained over time. IPL may be applied to treat blood circulatory diseases by inducing vasodilation and to improve blood flow. [ABSTRACT FROM AUTHOR]