Red Blood Cell Perfusion Research Articles

Workload and sex effects in comprehensive assessment of cutaneous microcirculation.

Workload and sex-related differences have been proposed as factors of importance when evaluating the microcirculation. Simultaneous assessments with diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) enable a comprehensive evaluation of the microcirculation. The aim of the study was to compare the response between sexes in the microcirculatory parameters red blood cell (RBC) tissue fraction, RBC oxygen saturation, average vessel diameter, and speed-resolved perfusion during baseline, cycling, and recovery, respectively. In 24 healthy participants (aged 20 to 30years, 12 females), cutaneous microcirculation was assessed by LDF and DRS at baseline, during a workload generated by cycling at 75 to 80% of maximal age-predicted heart rate, and recovery, respectively. Females had significantly lower RBC tissue fraction and total perfusion in forearm skin microcirculation at all phases (baseline, workload, and recovery). All microvascular parameters increased significantly during cycling, most evident in RBC oxygen saturation (34% increase on average) and perfusion (9-fold increase in total perfusion). For perfusion, the highest speeds (>10mm/s) increased by a factor of 31, whereas the lowest speeds (<1mm/s) increased by a factor of 2. Compared to a resting state, all studied microcirculation measures increased during cycling. For perfusion, this was mainly due to increased speed, and only to a minor extent due to increased RBC tissue fraction. Skin microcirculatory differences between sexes were seen in RBC concentration and total perfusion.

Microcirculatory tissue perfusion during general anaesthesia and noncardiac surgery: An observational study using incident dark field imaging with automated video analysis.

Handheld vital microscopy allows direct observation of red blood cells within the sublingual microcirculation. Automated analysis allows quantifying microcirculatory tissue perfusion variables - including tissue red blood cell perfusion (tRBCp), a functional variable integrating microcirculatory convection and diffusion capacities. We aimed to describe baseline microcirculatory tissue perfusion in patients presenting for elective noncardiac surgery and test that microcirculatory tissue perfusion is preserved during elective general anaesthesia for noncardiac surgery. Prospective observational study. University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 120 elective noncardiac surgery patients (major abdominal, orthopaedic or trauma and minor urologic surgery) and 40 young healthy volunteers. We measured sublingual microcirculation using incident dark field imaging with automated analysis at baseline before induction of general anaesthesia, under general anaesthesia before surgical incision and every 30 min during surgery. We used incident the dark field imaging technology with a validated automated analysis software. A total of 3687 microcirculation video sequences were analysed. Microcirculatory tissue perfusion variables varied substantially between individuals - but ranges were similar between patients and volunteers. Under general anaesthesia before surgical incision, there were no important changes in tRBCp, functional capillary density and capillary haematocrit compared with preinduction baseline. However, total vessel density was higher and red blood cell velocity and the proportion of perfused vessels were lower under general anaesthesia. There were no important changes in any microcirculatory tissue perfusion variables during surgery. In patients presenting for elective noncardiac surgery, baseline microcirculatory tissue perfusion variables vary substantially between individuals - but ranges are similar to those in young healthy volunteers. Microcirculatory tissue perfusion is preserved during general anaesthesia and noncardiac surgery - when macrocirculatory haemodynamics are maintained.

Laser Doppler Flowmetry Combined with Spectroscopy to Determine Peripheral Tissue Perfusion and Oxygen Saturation: A Pilot Study in Healthy Volunteers and Patients with Peripheral Arterial Disease.

Background: In this study, we assessed the ability of the EPOS system (Perimed AB, Järfälla, Stockholm, Sweden) to detect differences in tissue perfusion between healthy volunteers and patients with peripheral arterial disease (PAD) with different severity of disease. Methods: This single-center prospective pilot study included 10 healthy volunteers and 20 patients with PAD scheduled for endovascular therapy (EVT). EPOS measurements were performed at rest at 32 °C and 44 °C, followed by transcutaneous oxygen pressure (TcPo2) measurements. The measurements were performed on the dorsal and medial side of the foot, as well as the lateral side of the calf. EPOS parameters included hemoglobin oxygen saturation (HbSo2) and speed-resolved red blood cell (RBC) perfusion. Results: HbSo2 at 44 °C was significantly different between the three groups for all measurement locations. The overall speed-resolved RBC perfusion at 44 °C was statistically significant between the groups on the dorsal and medial side of the foot but not on the calf. TcPo2 values were not significantly different between the three groups. Conclusions: This study demonstrates that the EPOS system can depict differences in tissue perfusion between healthy volunteers, patients with Fontaine class IIb PAD, and those with Fontaine class III or IV PAD but only after heating to 44 °C.

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

BackgroundDescribe the outcome of adenovirus pneumonia in a pediatric intensive care unit (PICU) over a 3-year period, to identify the risk factors that may be associated with worse outcome.MethodsA retrospective observational study was performed in the PICU of children’s hospital in Shanghai from July 2016 to June 2019. Sixty-seven children over 29 days to 14 years old with adenovirus pneumonia who were admitted to PICU with acute hypoxemic respiratory failure were included in this study. The primary outcome was hospital mortality, and secondary outcomes were hospital and PICU length of stay (LOS), and risk factors of worse outcome.ResultsOf 67 children with severe adenovirus pneumonia, the hospital mortality was 16.42% (11/67) and 28-day mortality was 14.93% (10/67). Median Pediatric Risk of Mortality III (PRISM III) score at admission was 13 (interquartile range [IQR], 10–15). Median PICU LOS stay was 11 days (8-18d) and hospital LOS was 22 days (16-31d). Among children with extracorporeal membrane oxygenation (n = 9), 6 cases survived and 3 cases died. The patients who need renal replacement therapy, neuromuscular blockade, parenteral nutrition, and packed red blood cell perfusion had higher hospital mortality (p < 0.001, p = 0.041, p = < 0.001, p = 0.012, respectively). Multivariate logistic analysis indicated that liver dysfunction and nosocomial infection were associated with high risk of mortality.ConclusionsThe hospital mortality of adenovirus pneumonia in our PICU was 16.42%. Patients complicated liver dysfunction and co-infection & nosocomial infection were associated with poor outcome.

Automated quantification of tissue red blood cell perfusion as a new resuscitation target.

Identification of insufficient tissue perfusion is fundamental to recognizing circulatory shock in critically ill patients, and the primary target to restore adequate oxygen delivery. However, the concept of tissue perfusion remains ill-defined and out-of-reach for clinicians as point-of-care resuscitation target. Even though handheld vital microscopy (HVM) provides the technical prerequisites to collect information on tissue perfusion in the sublingual microcirculation, challenges in image analysis prevent quantification of tissue perfusion and manual analysis steps prohibit point-of-care application. The present review aims to discuss recent advances in algorithm-based HVM analysis and the physiological basis of tissue perfusion-based resuscitation parameters. Advanced computer vision algorithm such as MicroTools independently quantify microcirculatory diffusion and convection capacity by HVM and provide direct insight into tissue perfusion, leading to our formulation a functional parameter, tissue red blood cell (RBC) perfusion (tRBCp). Its definition is discussed in terms of the physiology of oxygen transport to the tissue and its expected effect as a point-of-care resuscitation target. Further refinements to microcirculatory monitoring include multiwavelength HVM techniques and maximal recruitable microcirculatory diffusion and convection capacity. tRBCp as measured using algorithm-based HVM analysis with an automated software called MicroTools, represents a promising candidate to assess microcirculatory delivery of oxygen for microcirculation-based resuscitation in critically ill patients at the point-of-care.

Monitoring tumor progression by mapping skin microcirculation with laser Doppler flowmetry.

Laser Doppler flow meter is a safe, useful, and noninvasive tool to monitor microvascular blood flow. It measures the changes in flow either over time or differences in flow over an area of skin or other exposed tissue. The primary function of LDF is to produce blood perfusion output signal that is proportional to the red blood cell perfusion (or flux). A simple analog-based laser Doppler flow meter is used to record the biosignals arising from the microvascular network of a surface lesion in the face of a human being. An innovative technique is developed to overcome one of the major technical limitations that involved removing the continuous artifacts or noise generated by the movement of the cable, the probe as well as the operator or the patient. A color heat map in MATLAB is created to facilitate its easy analysis, interpretation, and understanding of the blood flow changes over a period of time across a cross-sectional area in an image format processed after acquiring the biosignals (flux) using LDF by the clinicians or by the technician who is performing the vascular assessment of the lesion.

Quantitative comparisons between optical coherence tomography angiography and matched histology in the human eye

The aim was to quantitatively compare retinal vascular detail as seen on optical coherence tomography angiography (OCTA) and matched histology in the human eye. 13 normal human donor eyes were used. The central retinal artery was cannulated after which human packed red blood cells were perfused through the retinal vasculature. Retinal vessels were imaged using a custom-built OCTA device during red blood cell perfusion. The eye was subsequently perfused with endothelial cell antibodies and the flat-mounted retina studied histologically using a confocal scanning laser microscope. Qualitative and quantitative comparisons of retinal vascular information as seen on OCTA and histology from the same region of interest were performed. Gradable OCTA images were acquired from 4 of 13 eyes with mean postmortem-to-OCTA imaging time of 4.5 ± 1.3 h 23 pairs of OCTA-histology matched images were evaluated. The retinal arteries and veins had similar pixel intensity on OCTA images. The diameter of retinal veins was significantly greater than its paired artery on OCTA (P < 0.001). The density of vascular structures on OCTA (40.2% ± 10.1%) was significantly less than matched histology (52.1% ± 9.3%, P < 0.001). Mean capillary diameter on OCTA (10.2 ± 2.4 μm) was significantly greater than histology (8.2 ± 2.4 μm; P < 0.001). This is the first study to directly compare OCTA against histology from the same human eye. OCTA visualizes many of the vascular structures in the human retinal circulation but does not exactly match what is seen on histologic examination.

Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment

We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0–1mm/s, 1–10mm/s and above 10mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20–28years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.

Red blood cells induce necroptosis of lung endothelial cells and increase susceptibility to lung inflammation.

Red blood cell (RBC) transfusions are associated with increased risk of acute respiratory distress syndrome (ARDS) in the critically ill, yet the mechanisms for enhanced susceptibility to ARDS conferred by RBC transfusions remain unknown. To determine the mechanisms of lung endothelial cell (EC) High Mobility Group Box 1 (HMGB1) release following exposure to RBCs and to determine whether RBC transfusion increases susceptibility to lung inflammation in vivo through release of the danger signal HMGB1. In vitro studies examining human lung EC viability and HMGB1 release following exposure to allogenic RBCs were conducted under static conditions and using a microengineered model of RBC perfusion. The plasma from transfused and nontransfused patients with severe sepsis was examined for markers of cellular injury. A murine model of RBC transfusion followed by LPS administration was used to determine the effects of RBC transfusion and HMGB1 release on LPS-induced lung inflammation. After incubation with RBCs, lung ECs underwent regulated necrotic cell death (necroptosis) and released the essential mediator of necroptosis, receptor-interacting serine/threonine-protein kinase 3 (RIP3), and HMGB1. RIP3 was detectable in the plasma of patients with severe sepsis, and was increased with blood transfusion and among nonsurvivors of sepsis. RBC transfusion sensitized mice to LPS-induced lung inflammation through release of the danger signal HMGB1. RBC transfusion enhances susceptibility to lung inflammation through release of HMGB1 and induces necroptosis of lung EC. Necroptosis and subsequent danger signal release is a novel mechanism of injury following transfusion that may account for the increased risk of ARDS in critically ill transfused patients.

EPO reverses defective wound repair in hypercholesterolaemic mice by increasing functional angiogenesis

This study aims to elucidate the effect of erythropoietin (EPO) on the microcirculation during wound healing in mice genetically depleted of apolipoprotein E (ApoE(-/-)). The skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. Animals received Recormon(®) 1000 U kg(-1) body weight (BW) intra-peritoneally (i.p.) at day 1, 3, 5, 7, 9 and 11 post-wounding at a concentration of 100 Uml(-1) (n=42). Normal healing and vehicle-treated wild type animals (WT) served as controls. The microcirculation of the wound was analysed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Microtomography (micro-CT) analysis of casted wound microvessels was performed allowing three-dimensional (3D) histomorphometric analysis. Tissue samples were examined ex vivo for wound scoring and for expression analysis of EPO-Receptor (Epo-R) and endothelial nitric oxide synthase (eNOS). Upon EPO treatment, the total wound score in ApoE(-/-) mice was increased by 23% on day 3, by 26% on day 7 and by 18% on day 13 when compared to untreated ApoE(-/-) mice (all P<0.05 vs. vehicle). Improved wound healing was accompanied with a significant increase of functional angiogenetic density and angiogenetic red blood cell perfusion on days 5, 7, 9 and 11 post-wounding. 3D histomorphometric analysis revealed an increase of vessel thickness (1.7-fold), vessel volume (2.4-fold) and vessel surface (1.7-fold) (all P<0.05 vs. vehicle). In addition, improved wound healing was associated with enhanced Epo-R expression (4.6-fold on day 3 and 13.5-fold on day 7) and eNOS expression (2.4-fold on day 7) (all P<0.05 vs. vehicle). Our data demonstrate that repetitive systemic EPO treatment reverses microvascular dysfunction during wound healing in hypercholesterolaemic mice by inducing new vessel formation and by providing the wound with more oxygen.

Erythrocytes: surveyors as well as purveyors of oxygen?

for more than a century a large body of evidence has accumulated in the physiological and pathophysiological literature to support the close relationship between the demand of oxygen by the tissues and the supply of oxygen by the cardiorespiratory system. When the demand for oxygen changes, how is

Erythropoietin improves wound healing by increasing red blood cell perfusion in hypercholesteremic mice

Inadequate blood supply is the most common cause of altered wound healing representing a considerable source of morbidity in daily plastic surgery practice. Erythropoietin (EPO) is intensively investigated for its nonhematopoietic vasculoprotective effects. The present study demonstrates the potential of repetitive systemical EPO treatment to accelerate angiogenesis in hypercholesteremic and microangiopathic murine ischemic wounds.

Percutaneous Window Chamber Method for Chronic Intravital Microscopy of Sensor—Tissue Interactions

A dorsal, two-sided skin-fold window chamber model was employed previously by Gough in glucose sensor research to characterize poorly understood physiological factors affecting sensor performance. We have extended this work by developing a percutaneous one-sided window chamber model for the rodent dorsum that offers both a larger subcutaneous area and a less restrictive tissue space than previous animal models. A surgical procedure for implanting a sensor into the subcutis beneath an acrylic window (15 mm diameter) is presented. Methods to quantify changes in the microvascular network and red blood cell perfusion around the sensors using noninvasive intravital microscopy and laser Doppler flowmetry are described. The feasibility of combining interstitial glucose monitoring from an implanted sensor with intravital fluorescence microscopy was explored using a bolus injection of fluorescein and dextrose to observe real-time mass transport of a small molecule at the sensor-tissue interface. The percutaneous window chamber provides an excellent model for assessing the influence of different sensor modifications, such as surface morphologies, on neovascularization using real-time monitoring of the microvascular network and tissue perfusion. However, the tissue response to an implanted sensor was variable, and some sensors migrated entirely out of the field of view and could not be observed adequately. A percutaneous optical window provides direct, real-time images of the development and dynamics of microvascular networks, microvessel patency, and fibrotic encapsulation at the tissue-sensor interface. Additionally, observing microvessels following combined bolus injections of a fluorescent dye and glucose in the local sensor environment demonstrated a valuable technique to visualize mass transport at the sensor surface.

The Effect of Sickle Red Blood Cell Adhesion on Gene Expression in a PAF-Pre-Treated Microcirculatory Bed.

The expression profile of a number of genes in the rat mesocecum linked to sickle (SS) red blood cell (RBC) adhesion was examined by microarray analysis. The abnormal adherence of SS RBC to the vascular endothelium has been proposed to play an important role in vaso-occlusion in a double capacity; first, by actual physical blockage of the post capillary venules and, second, by inducing the expression of pleiotropic genes that could lead to further modification of the SS phenotype. The goals of these experiments were to identify these pleiotropic genes expressed upon adhesion of SS RBC, to understand how they contribute to the SS phenotype and, to identify potential targets for therapy. The rat mesocecum preparation was prepared as described (Kaul et al, Blood 95:368, 2000) and platelet activating factor (PAF) was used to induce endothelial adhesion receptors to accentuate human SS RBC binding. Rat cecum/ mesocecum RNA was prepared by Qiagen RNeasy mini-kit and fluorescent labeled cDNA hybridized to 32K oligonucleotide microarrays followed by analysis using Gene Pix Pro 4.1. The effect of SS RBC perfusion on PAF-treated tissues vs untreated tissues was compared to PAF-only tissues vs untreated tissues using hierarchical clustering. SS RBC adhesion was analyzed as a function of venular diameter and was significantly different (p<0.00001) in the PAF treated tissues as revealed by a significantly higher Y-intercept (work quoted above). Of the 533 transcripts that were up-regulated and 353 transcripts that were down-regulated more than 2 fold, 68 were up-regulated and 32 were down-regulated more than 4-fold; of this subset, 91 transcripts were compared by Cluster analysis. Many of the up-regulated genes detected in the PAF treated SS RBC adherent tissues were associated with inflammation such as phospholipase A2, group IIA; glutathione peroxidase 2; sialyltransferase 4C; and integrin beta 4. Interestingly, a number of proteasome subunits and ubiquitin D were also highly up-regulated; these genes were only present in the SS RBC perfused PAF treated mesocecum and could then be considered potential targets for specific therapies e.g. proteasome inhibitors. Recent studies also indicate that the ubiquitin system controls NF-kappaB pathways that, in turn, control integrin expression that can increase cell adhesion. The genes that were down-regulated included apolipoprotein B; cytochrome P450 Cyp4b1; cyclin G associated kinase; and metallothionein 2 (MT2). The down-regulation of MT2 is interesting because it is known to be highly regulated in response to the plasma zinc concentration; due to the chronic inflammatory/oxidative condition present in SS disease, zinc may be depleted and feedback negatively on MT2 synthesis. SS RBC adhesion however, not just PAF treatment, is necessary for MT2 downregulation and may, paradoxically, increase zinc availability since MT expression and zinc depletion are inversely correlated. Overall, the results suggest that SS RBC adhesion regulates a number of mesocecum genes involved in the inflammatory response, regulation of oxidative damage, increased intracellular protein degradation, decreased vesicular transport and regulation of zinc ion concentration. These pleiotropic genes are candidates for epistatic (modifier) genes if found to be polymorphic in different individuals and ethnicities. Enhancing or interfering with these specific genes or metabolic pathways may open up new therapeutic strategies for SS disease.

Mapping of the functional microcirculation in vital organs using contrast-enhanced in vivo video microscopy.

A functional microcirculation is vital to the survival of mammalian tissues. In vivo video microscopy is often used in animal models to assess microvascular function, providing real-time observation of blood flow in normal and diseased tissues. To extend the capabilities of in vivo video microscopy, we have developed a contrast-enhanced system with postprocessing video analysis tools that permit quantitative assessment of microvascular geometry and function in vital organs and tissues. FITC-labeled dextran (250 kDa) was injected intravenously into anesthetized mice to provide intravascular fluorescence contrast with darker red blood cell (RBC) motion. Digitized video images of microcirculation in a variety of internal organs (e.g., lung, liver, ovary, and kidney) were processed using computer-based motion correction to remove background respiratory and cardiac movement. Stabilized videos were analyzed to generate a series of functional images revealing microhemodynamic parameters, such as plasma perfusion, RBC perfusion, and RBC supply rate. Fluorescence contrast revealed characteristic microvascular arrangements within different organs, and images generated from video sequences of liver metastases showed a marked reduction in the proportion of tumor vessels that were functional. Analysis of processed video sequences showed large reductions in vessel volume, length, and branch-point density, with a near doubling in vessel segment length. This study demonstrates that postprocessing of fluorescence contrast video sequences of the microcirculation can provide quantitative images useful for studies in a wide range of model systems.

Improved Myoglobin Saturation Measurement Made by Partial Least-Squares Analysis of Optical Reflectance Spectra

Accurate myoglobin oxygen saturation determination from tissue using optical spectral analysis has been limited by overlap in spectral features between myoglobin and hemoglobin. Partial least-squares analysis of reflectance spectra has been successfully used to predict myoglobin oxygen saturation from blood perfused hearts, although uncertainty remains as to how much error in the myoglobin saturation estimate occurs due to hemoglobin contamination. This study was undertaken to quantify the error due to hemoglobin in the partial least-squares estimate of myoglobin saturation. Calibration spectra were developed by mathematical addition of individually acquired in vitro reflectance spectra from various absorbing species in scattering media. The isolated perfused guinea pig heart model was used to allow for switching between crystalloid and red blood cell perfusion in a beating heart. Inclusion of cytochrome c and cytochrome oxidase in a calibration set containing hemoglobin and myoglobin improved the accuracy of the partial least-squares analysis of myoglobin saturation. Both the Mahalanobis distance test and the residual ratio test demonstrated improved representation of spectra obtained from the heart using a calibration set that included both cytochromes. A 4.3% error in myoglobin oxygen saturation measurements was determined.

Effects of venous pressure and posture on skin capillary perfusion.

Various vasoconstriction mechanisms after a change in posture are involved in controlling skin blood flow and capillary transmural pressure to maintain adequate transcapillary exchange. The role of venous orthostatic pressure in the regulation of capillary nutritive perfusion, however, is less clear. We investigated capillary perfusion in 30 healthy subjects using intravital capillary microscopy of the big toenail-fold. Measurements were made in the supine and the sitting positions before and after incremental elevation of venous resistance, and thus the pre- to post-capillary pressure difference, by inflating a cuff around the ankle. On dependency, median capillary density rose (P < 0.0001), whereas red blood cell perfusion decreased (P < 0.0001). Cuff inflation of 30-60 mmHg in the supine position induced similar phenomena. Repeatedly, the same capillaries were found to be recruited after an increase in transmural pressure. We conclude that post-capillary pressure appears to be an important factor in the regulation of capillary perfusion, because an increase in venous resistance mimics the effects of dependency. The findings in this study support the theory of 'minimum perfusion pressure' for each capillary to be perfused with erythrocytes.

Heterogeneity of red blood cell perfusion in capillary networks supplied by a single arteriole in resting skeletal muscle.

Flow heterogeneity within capillary beds may have two sources: (1) unequal distribution of red blood cell (RBC) supply among arterioles and (2) unique properties of RBC flow in branching networks of capillaries. Our aim was to investigate the capillary network as a source of both spatial and temporal heterogeneity of RBC flow. Five networks, each supplied by a single arteriole, were studied in frog sartorius muscle (one network per frog) by intravital video microscopy. Simultaneous data on RBC velocity (millimeters per second), lineal density (RBCs per millimeter), and supply rate (RBCs per second) were measured continuously (10 samples per second) from video recordings in 5 to 10 capillary segments per network for 10 minutes by use of automated computer analysis. To quantify heterogeneity, mean values from successive 10-second intervals were tabulated for each flow parameter in each capillary segment (ie, portion of capillary between successive bifurcations), and percent coefficient of variation (SD/mean.100%) was calculated for (1) spatial heterogeneity among vessels (CVs) every 10 seconds and for the entire 10-minute sample and (2) temporal heterogeneity within vessels for every capillary segment and for the mean flow parameter. Analysis of these data indicates that (1) capillary networks are a significant source of both spatial and temporal flow heterogeneity, and (2) continuous redistributions of flow occur within networks, resulting in substantial temporal changes in CVs, although a persistent spatial heterogeneity of perfusion still exists on a 10-minute basis. In most networks, CVs decreased as supply rate within the network increased, thus indicating that rheology plays a significant role in determining the perfusion heterogeneity.