Sidestream Dark Field Imaging Research Articles

Predictive value of microcirculation for pediatric extracorporeal membrane oxygenation weaning test: Amonocentric prospective observational study.

Extracorporeal membrane oxygenation (ECMO) is widely used for children treated for refractory respiratory failures or refractory cardiogenic shock. Its duration depends on organ functions recovery. Weaning is decided using macro-circulatory tools, but microcirculation is not well evaluated. Sidestream dark-field video imaging is used to assess the perfusion of the sublingual microvascular vessels. The aim of this study was to assess the predictive value of microcirculatory indices in ECMO weaning. This prospective monocentric study examined pediatric patients at Trousseau Hospital between March 2017 and December 2020. The study included all patients from 35 weeks of gestational age to 18 years old who were treated with ECMO. Children were divided into two groups: one with stability after weaning and the other with instability after weaning. We collected clinical and biological data, ventilation parameters, extracorporeal membrane oxygenation parameters, and drugs used at admission and after the weaning test. Microcirculations videos were taken after weaning trials with echocardiography and blood gas monitoring. The study included 30 patients with a median age of 29 days (range: 1-770 days) at admission, including 18 patients who received venoarterial ECMO (60%). There were 19 children in the stability group and 11 in the instability group. Macrocirculatory and microcirculatory indices showed no differences between groups. The microvascular flow index was subnormal in both groups (2.3 (1.8-2.4) and 2.3 (2.3-2.6), respectively; p = 0.24). The microvascular indices were similar between cases of venovenous and venoarterial ECMO and between age groups. Microcirculation monitoring at the weaning phase did not predict the failure of ECMO weaning.

A multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model

Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters.Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature – tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured.Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters.In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.

(415) - Microvascular Responses to Donor Specific HLA Antibodies in Heart Transplantation. Sidestream Dark Field Imaging Results

(415) - Microvascular Responses to Donor Specific HLA Antibodies in Heart Transplantation. Sidestream Dark Field Imaging Results

Intraoperative intravenous infusion of lidocaine increases total and small vessel densities of sublingual microcirculation: a randomized prospective pilot study

Objective Multiple organ failure can occur as a result of postoperative complications. Research has indicated that the underlying mechanism of organ dysfunction is a microcirculation disorder. Because of its antioxidant and anti-inflammatory properties, lidocaine has the potential to improve microvascular blood flow. This study was performed to assess the effect of intraoperative intravenous lidocaine infusion on the microcirculation and determine the incidence of postoperative complications. Methods In this prospective randomized double-blind pilot study, 12 patients scheduled for abdominal surgery were randomly allocated to receive an intraoperative infusion of either 1% lidocaine or the same volume of 0.9% sodium chloride solution. The microcirculation was monitored using sidestream dark-field imaging and the vascular occlusion test combined with near-infrared spectroscopy. Results Lidocaine significantly increased the total vascular density and small vessel density after 2 hours of infusion, with preservation of 99% to 100% of the capillary perfusion in both groups. No patients developed organ failure. Conclusions An increase in vessel density may be beneficial in major abdominal surgeries because it is associated with better tissue perfusion and oxygen delivery. However, this finding requires further investigation in patients with increased surgical risk. Overall, this study indicates that lidocaine has potential to improve microvascular perfusion. Research Registry number: 9549 ( https://www.researchregistry.com/browse-the-registry#home/registrationdetails/650ffd27b3f547002bd7635f/ )

Sublingual microcirculation in healthy pediatric population using the sidestream dark-field imaging method.

The sidestream dark-field imaging method is used to study microcirculation. Normal values of sublingual microcirculation parameters in healthy children of different age and gender categories are unknown. The study's main goal was to determine normal values of selected parameters of sublingual microcirculation in healthy children of different age and gender categories. 40 healthy children were measured, ten aged 3-5.9 years, ten aged 6-10.9 years, ten aged 11-14.9 years, and ten aged 15-18.9 years. After recording the basic anthropometric parameters and vital functions, each volunteer had their microcirculation measured using an SDF probe placed sublingually. Three video clips were recorded and processed offline, and the three best and most stable parts of each were analyzed. Total vascular density, small vessel density, proportion of perfused small vessels, perfused vessel density, perfused small vessel density, and DeBacker's score were significantly higher in females than in males. There were no differences between age groups in microcirculation parameters except MFI. Age does not influence normal values of microcirculatory parameters. Female gender was associated with higher vessel density, perfused vessel density, and DeBacker's score. A suggestion of the normal range of microcirculatory parameters in healthy children is provided.

Sidestream dark field imaging and biomarker evaluation reveal minimal significant changes to the microcirculation and glycocalyx in a canine hemorrhagic shock model.

To investigate the effects of hemorrhagic shock and fresh whole blood resuscitation on the microcirculation and endothelial glycocalyx using sidestream dark field (SDF) imaging and plasma biomarkers. 8 purpose-bred dogs. Pressure-targeted hemorrhagic shock was induced in anesthetized dogs. SDF measurement of perfused boundary region and microcirculatory variables (RBC flow, total vessel density, and relative and absolute capillary blood volume), biomarker measurement (heparan sulfate, hyaluronan, VE-cadherin, and syndecan-1), mean arterial blood pressure, and cardiac output measurement were performed before anesthesia (TP0), after induction (TP1), after hemorrhagic shock (TP2), and after 50% retransfusion (TP3) and 100% retransfusion (TP4). At TP1, TP2, TP3, and TP4, mean arterial blood pressure was 74.25 ± 7.17 mm Hg, 49.50 ± 13.74 mm Hg, 63.50 ± 13.29 mm Hg, and 71.38 ± 8.77 mm Hg, and cardiac output was 2.57 ± 1.01 L/min, 0.8 ± 0.36 L/min, 1.81 ± 0.57 L/min, and 2.93 ± 1.22 L/min, respectively. Heparan sulfate, hyaluronan, syndecan-1, and VE-cadherin ranges were 24.80 to 77.72 ng/mL, 5.77 to 105.06 ng/mL, below detection to 1,545.69 pg/mL, and 0 to 2.52 ng/mL, respectively. Perfused boundary region, RBC flow, total vessel density, and relative and absolute capillary blood volume ranges were 1.75 to 2.68 µm, 89.6 to 584.5 µm/s, 51.7 to 1,914.3 mm/m2, 0.94 to 1.53 103 μm3, and 1.50 to 94.30 103 μm3, respectively. Heparan sulfate decreased significantly over time (P = .016). No significant differences were found for microcirculatory variables, perfused boundary regions, or other biomarkers. This was the first study to assess microvascular dysfunction and endothelial shedding in a canine hemorrhagic shock model using SDF microscopy (Glycocheck) and plasma biomarkers. Further studies are needed to determine clinical relevance.

Liposomal nanocarriers of preassembled glycocalyx expeditiously restore endothelial glycocalyx in endotoxemia.

The endothelial glycocalyx (EG) is degraded early during sepsis, and currently available treatments are not effective in promptly restoring it. Here, we created liposomal nanocarriers of preassembled glycocalyx (LNPG) by synthesizing glycosylated syndecan-1 and inserting it into the lipid membrane of unilamellar liposomes. We hypothesized that LNPG would fuse with the endothelial cells where EG is degraded and restore EG in sepsis. We induced endotoxemia in C57BL/6J mice using lipopolysaccharides (LPS) and treated them with LNPG, saline, syndecan-1, or liposomes. LNPG significantly prolonged the survival time of LPS-treated mice compared with the other treatments. Immunostaining of en face mesenteric arteries of LPS-treated mice showed that syndecan-1 was fully restored after LNPG administration. In addition, EG height in microvasculature of mouse cremaster muscle was monitored using sidestream dark field imaging. LNPG restored the perfused boundary region (PBR), which is inversely related to EG dimensions, to the control level after LPS administration. Furthermore, flow-induced dilation in isolated mouse mesenteric arterioles was fully recovered after LNPG treatment in LPS-treated mice. In summary, our findings provide evidence of the therapeutic efficacy of LNPG in the LPS-induced mouse model of sepsis, achieved by expeditiously restoring EG through fusion of LNPG with the endothelial plasma membrane and recovery of endothelial function.NEW & NOTEWORTHY Vascular endothelial cells represent the first line of exposure to bacterial endotoxins. Here, we propose a novel therapeutic strategy using liposomes to deliver preassembled glycocalyx to vascular endothelial cell surface and consequently restore endothelial glycocalyx (EG). We tested liposomal nanocarriers of preassembled glycocalyx (LNPG) in vivo and ex vivo to establish for the first time their expeditious therapeutic efficacy in improving survival of lipopolysaccharides (LPS)-treated mice, as achieved by the restoration of EG and recovery of endothelial function.

Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity study

BackgroundMicrovascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. ObjectivesWe sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. MethodsUsing baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. ResultsThere was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). ConclusionWe revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.

Real-time semi-quantitative assessment of anastomotic blood perfusion in mini‑invasive rectal resections by Sidestream Dark Field (SDF) imaging technology: a prospective in vivo pilot study.

Anastomotic leakage (AL) is one of the severe complications after rectal surgery, and anastomotic ischemia is one of the main factors. This prospective in vivo pilot study aimed to evaluate the effectiveness of Sidestream Dark Field (SDF) imaging in quantitative assessment of anastomotic microcirculation and to analyze its correlation with AL. Thirty-three patients with rectal cancer who underwent laparoscopic low anterior resection from 2019 to 2020 were enrolled. Microcirculation was measured by SDF imaging at the descending colon, the mesocolon transection line (MTL), and 1cm and 2cm distal to the MTL. Anastomotic microcirculation was measured at the stapler anvil edge before anastomosis. Quantitative perfusion-related parameters were as follows: microcirculation flow index (MFI), perfused vessel density (PVD), proportion of perfused vessels (PPV), and total vessel density (TVD). All patients obtained stable microcirculation images. Functional microcirculation parameters (MFI, PPV, PVD) decreased successively from the descending colon, the colon at MTL, and 1cm and 2cm distal to the MTL (all P < 0.01). Extremely poor microcirculation was found at the intestinal segment 2cm distal to the MTL. Micro-perfusion was significantly lower at the colonic limb of the anastomosis compared with the descending colon (all P < 0.001). Anastomotic leakage occurred in 3 patients (9.1%) whose anastomotic microcirculation was significantly lower than those without AL (all P < 0.01). Blood perfusion at the colonic limb of the anastomosis was significantly higher in patients with left colic artery preservation than in controls. SDF imaging is a promising technique for evaluating anastomotic microcirculation and has potential clinical significance for risk stratification of AL.

Dl-3-n-butylphthalide improves intestinal microcirculation disorders in septic rats by regulating the PI3K/AKT signaling pathway and autophagy.

Sepsis has complex pathophysiological mechanisms that bring new challenges in the treatment of sepsis at a time when the intestinal microcirculation in sepsis is receiving increasing attention. Dl-3-n-butylphthalide (NBP), which is a drug that can improve multiorgan ischemic diseases, is also worth examining to improve the intestinal microcirculation in sepsis. In this study, male Sprague-Dawley rats were divided into the sham group (n=6), CLP group (n=6), NBP group (n=6) and NBP+LY294002 group (n=6). The rat model of severe sepsis was established by cecal ligation and puncture (CLP). Abdominal wall incisions and sutures were performed in the first group, and CLP was performed in the latter three groups. Normal saline/NBP/NBP+LY294002 solution was injected intraperitoneally 2h or 1h before modeling. Hemodynamic data (blood pressure and heart rate) were recorded at 0, 2, 4 and 6h. Sidestream dark field (SDF) imaging and the Medsoft System were used to observe the intestinal microcirculation of rats and obtain data at 0, 2, 4, and 6h. Six hours after the model was established, the serum levels of TNF-α and IL-6 were measured to evaluate the level of systemic inflammation. Pathological damage to the small intestine was evaluated by electron microscopy and histological analysis. The expression levels of P-PI3K, PI3K, P-AKT, AKT, LC3 and p62 in the small intestine were analyzed by Western blotting. The expressions of P-PI3K, P-AKT, LC3 and P62 in small intestine were detected by immunohistochemical staining. NBP improved intestinal microcirculation disturbances in septic rats, alleviated the systemic inflammatory response, reduced the destruction of the small intestinal mucosa and the disruption of microvascular endothelial cells, and alleviated autophagy in vascular endothelial cells. NBP increased the ratio of P-PI3K/total PI3K, P-AKT/total AKT, and P62/β-actin and decreased the ratio of LC3 II/LC3 I. NBP ameliorated intestinal microcirculation disturbances and the destruction of small intestinal vascular endothelial cells in septic rats by activating the PI3K/Akt signaling pathway and regulating autophagy.

Non-invasive techniques to access in vivo the skin microcirculation in patients.

The microcirculation is composed of blood vessels with mean internal diameter smaller than 100 μm. This structure is responsible for survival of cells and in the last 50 years its study has become increasingly interesting because it often participates in the pathophysiology of several diseases or can determine better or worse prognosis for them. Due to the growing importance of knowing more about the microcirculation, several techniques have been developed and now it is possible to study its structure or function. In the last 25 years, the cutaneous microcirculation has emerged as an accessible and representative portion of generalized vascular bed allowing the examination of mechanisms of microcirculatory function and dysfunction. This mini review presents several techniques used for non-invasive access to skin microcirculation, such as Nailfold Videocapillaroscopy, Orthogonal Polarization Spectral Imaging, Sidestream Dark Field Imaging, Incident Dark field Illumination, Laser Doppler Flowmetry, and Laser Speckle Contrast Imaging applied. The techniques presented will describe which types of variables (structural or functional) can be evaluated, their limitations and potential uses.

A new convolutional neural network-construct for sepsis enhances pattern identification of microcirculatory dysfunction

BackgroundTriggers of organ dysfunction have been associated with the worsening of microcirculatory dysfunction in sepsis, and because microcirculatory changes occur before macro-hemodynamic abnormalities, they can potentially detect disease progression early on. The difficulty in distinguishing altered microcirculatory characteristics corresponding to varying stages of sepsis severity has been a limiting factor for the use of microcirculatory imaging as a diagnostic and prognostic tool in sepsis. The aim of this study was to develop a convolutional neural network (CNN) based on progressive sublingual microcirculatory dysfunction images in sepsis, and test its diagnostic accuracy for these progressive stages. MethodsSepsis was induced in Wistar rats (2 mL of E. coli 108 CFU/mL inoculation into the jugular vein), and 2 mL saline injection in sham animals was the control. Sublingual microvessels of all animals with surrounding tissue images were captured by Sidestream dark field imaging (SDF) at T0 (basal) and T2, T4, and T6 h after sepsis induction. From a total of 137 videos, 37.930 frames were extracted; a part (29.341) was used for the training of Resnet-50 (CNN-construct), and the remaining (8.589) was used for validation of accuracy. ResultsThe CNN-construct successfully classified the various stages of sepsis with a high accuracy (97.07%). The average AUC value of the ROC curve was 0.9833, and the sensitivity and specificity ranged from 94.57% to 99.91%, respectively, at all time points. ConclusionsBy blind testing with new sublingual microscopy images captured at different periods of the acute phase of sepsis, the CNN-construct was able to accurately diagnose the four stages of sepsis severity. Thus, this new method presents the diagnostic potential for different stages of microcirculatory dysfunction and enables the prediction of clinical evolution and therapeutic efficacy. Automated simultaneous assessment of multiple characteristics, both microvessels and adjacent tissues, may account for this diagnostic skill. As such a task cannot be analyzed with human visual criteria only, CNN is a novel method to identify the different stages of sepsis by assessing the distinct features of each stage.

Fluid resuscitation, but not inhaled nitric oxide, improves microcirculation in septic pigs.

Prolonged deterioration of microvascular flow during sepsis leads to organ dysfunction. Capillary flow restoration may prevent this complication. The main aim of this study was to investigate the microcirculatory effects of inhaled nitric oxide (iNO) combined with intravenous hydrocortisone in a porcine model of sepsis. The 2nd aim was to evaluate the influence of hemodynamic resuscitation with noradrenaline and crystalloids on capillary flow. Eleven piglets of Polish breed underwent surgical colon perforation to develop sepsis. They were randomly allocated to one of 3 treatment groups. Group 1 received iNO and hydrocortisone, whereas group 2 did not. Both groups were resuscitated with crystalloids and noradrenaline if hypotensive. Group 3 received no treatment at all. During a 30-hour observation, we assessed the microcirculation using sidestream dark field imaging (SDF). We found no effect of iNO with hydrocortisone on the microcirculation. Fluid and vasopressor treatment led to a higher microcirculatory flow index after 20 h of observation (3 and 2.75 in groups 1 and 2 compared to 1.9 in group 3), a greater proportion of perfused vessels (94% and 87% compared to 63% in groups 1, 2 and 3, respectively) and a greater perfused vessel density (15.2 mm/mm2, 15.09 mm/mm2 and 10.1 mm/mm2 in groups 1, 2 and 3, respectively). Crystalloid and vasopressor treatment postponed microvascular flow derangements, whereas iNO combined with intravenous hydrocortisone did not improve microvascular perfusion.

Endothelial Damage and the Microcirculation in Critical Illness.

Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.

Multimodal measurement of glycocalyx degradation during coronary artery bypass grafting.

Glycocalyx shedding and subsequent endothelial dysfunction occur in many conditions, such as in sepsis, in critical illness, and during major surgery such as in coronary artery bypass grafting (CABG) where it has been shown to associate with organ dysfunction. Hitherto, there is no consensus about the golden standard in measuring glycocalyx properties in humans. The objective of this study was to compare different indices of glycocalyx shedding and dysfunction. To this end, we studied patients undergoing elective CABG surgery, which is a known cause of glycocalyx shedding. Sublingual glycocalyx thickness was measured in 23 patients by: 1) determining the perfused boundary region (PBR)-an inverse measure of glycocalyx thickness-by means of sidestream dark field imaging technique. This is stated double, 2) measuring plasma levels of the glycocalyx shedding products syndecan-1, hyaluronan, and heparan sulfate and 3) measuring plasma markers of impaired glycocalyx function and endothelial activation (Ang-2, Tie-2, E-selectin, and thrombomodulin). Measurements were performed directly after induction, directly after onset of cardiopulmonary bypass (CPB), and directly after cessation of CPB. We assessed changes over time as well as correlations between the various markers. The PBR increased from 1.81 ± 0.21 μm after induction of anesthesia to 2.27 ± 0.25 μm (p < 0.0001) directly after CPB was initiated and did not change further during CPB. A similar pattern was seen for syndecan-1, hyaluronan, heparan sulfate, Ang-2, Tie-2, and thrombomodulin. E-selectin levels also increased between induction and the start of CPB and increased further during CPB. The PBR correlated moderately with heparan sulfate, E-selectin, and thrombomodulin and weakly with Syndecan-1, hyaluronan, and Tie-2. Shedding markers syndecan-1 and hyaluronan correlated with all functional markers. Shedding marker heparan sulfate only correlated with Tie-2, thrombomodulin, and E-selectin. Thrombomodulin correlated with all shedding markers. Our results show that glycocalyx thinning, illustrated by increased sublingual PBR and increased levels of shedding markers, is paralleled with impaired glycocalyx function and increased endothelial activation in CABG surgery with CPB. As correlations between different markers were limited, no single marker could be identified to represent the glycocalyx in its full complexity.

Variability of microcirculatory measurements in healthy volunteers

Reliable assessment of the microcirculation is important to investigate microcirculatory properties in various disease states. The GlycoCheck system automatically analyzes sublingual sidestream dark field images to determine the perfused boundary region (PBR; a measure of glycocalyx thickness), red blood cell filling percentage, and microvascular vessel density. Although GlycoCheck has been used to study the microcirculation in patients, little is known about the reproducibility of measurements in healthy volunteers. We assessed intra- and interobserver agreement by having two experienced observers perform three consecutive microcirculation measurements with the GlycoCheck system in 49 healthy volunteers. Intraobserver agreement of single measurements were poor (intraclass correlation coefficients (ICCs) < 0.4) for PBR, red blood cell filling percentage and microvascular vessel density. ICCs increased to values > 0.6 (indicating good reproducibility) for all parameters when performing and averaging three consecutive measurements. No systematic differences were observed between observers for any parameter. Interobserver variability was fair for PBR (ICC = 0.53) and red blood cell filling percentage (ICC = 0.58) and poor for perfused vessel density (ICC = 0.20). In conclusion, GlycoCheck software can be used with acceptable reliability and reproducibility for microcirculation measurements on a population level when averaging three consecutive measurements. Repeated measurements are preferably performed by the same observer.

Microvascular perfusion, perfused boundary region and glycocalyx shedding in patients with autosomal dominant polycystic kidney disease: results from the GlycoScore III study.

Vascular abnormalities and endothelial dysfunction are part of the spectrum of autosomal dominant polycystic kidney disease (ADPKD). The mechanisms behind these manifestations, including potential effects on the endothelial surface layer (ESL) and glycocalyx integrity, remain unknown. Forty-five ambulatory adult patients with ADPKD were enrolled in this prospective, observational, cross-sectional, single-centre study. Fifty-one healthy volunteers served as a control group. All participants underwent real-time microvascular perfusion measurements of the sublingual microcirculation using sidestream dark field imaging. After image acquisition, the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration into the ESL, was automatically calculated. Microvascular perfusion was assessed by RBC filling and capillary density. Concentrations of circulating glycocalyx components were determined by enzyme-linked immunosorbent assay. ADPKD patients showed a significantly larger PBR compared with healthy controls (2.09±0.23µm versus 1.79±0.25µm; P<.001). This was accompanied by significantly lower RBC filling (70.4±5.0% versus 77.9±5.4%; P<.001) as well as a higher valid capillary density {318/mm2 [interquartile range (IQR) 269-380] versus 273/mm2 [230-327]; P=.007}. Significantly higher plasma concentrations of heparan sulphate (1625±807ng/ml versus 1329±316ng/ml; P=.034), hyaluronan (111ng/ml [IQR 79-132] versus 92ng/ml [82-98]; P=.042) and syndecan-1 were noted in ADPKD patients compared with healthy controls (35ng/ml [IQR 27-57] versus 29ng/ml [23-42]; P=.035). Dimensions and integrity of the ESL are impaired in ADPKD patients. Increased capillary density may be a compensatory mechanism for vascular dysfunction to ensure sufficient tissue perfusion and oxygenation.

Ephedrine vs. phenylephrine effect on sublingual microcirculation in elderly patients undergoing laparoscopic rectal cancer surgery.

BackgroundThe effects of anesthesia administration on sublingual microcirculation are unknown. It is unclear how sublingual microcirculation responds to ephedrine or phenylephrine administration. We hypothesized that microvascular perfusion is impaired under anesthesia.Materials and methodsWe randomly divided 100 elderly patients undergoing laparoscopic rectal cancer surgery into phenylephrine and ephedrine groups in a 1:1 ratio. Ephedrine or phenylephrine was administered when MAP was < 80% for > 1 min. The heart rate (HR) and mean arterial pressure (MAP) were recorded every 5 min. Lactic acid was tested both pre- and postoperatively. The sublingual microcirculation characteristics of the microvascular flow index, the percentage of perfused vessels, the density of perfused vessels, and the heterogeneity index were monitored using a sidestream dark field imaging device.ResultsTheir MAP showed an evident decrease of > 20%. At this point, the HR, microvascular flow index, perfused vessel density, and proportion of perfused vessels decreased similarly in ephedrine and phenylephrine groups. Conversely, the heterogeneity index increased in both groups. After phenylephrine and ephedrine administration, ephedrine treatment significantly increased the proportion of perfused vessels, microvascular flow index, and HR compared with phenylephrine treatment.ConclusionGeneral anesthesia was associated with reduced MAP, HR, and sublingual microcirculation in elderly patients undergoing laparoscopic rectal cancer surgery. The results of ephedrine treatment were better than those of phenylephrine treatment in terms of HR, increased the proportion of perfused vessels, and microvascular flow index of sublingual microcirculation.Clinical trial registration[www.ClinicalTrials.gov], identifier [ChiCTR-2000035959].

Perfused boundary region as biomarker for endothelial integrity in former preterms in adolescence.

Extremely low birth weight (ELBW) survivors have microvascular structural differences already described in kidney and retina, suggesting changes in endothelial integrity. A biomarker of endothelial integrity is perfused boundary region (PBR), which measures glycocalycal thickness. The endothelial glycocalyx is a complex, highly versatile structure with essential roles in vascular integrity and function. We explored PBR patterns together with other microvascular markers in healthy controls and former ELBW children. In the PREMATCH cohort (87 healthy controls, 93 ELBW survivors), we assessed endothelial integrity by calculating PBR (sidestream dark-field imaging), several microvascular markers (blood pressure, estimated glomerular filtration rate (eGFRcysC)), and retinal imaging in early adolescence. We explored differences between both groups, and searched for perinatal determinants of PBR and correlations between different microvascular markers. We provided reference values for PBR (average 1.90 µm, SD 0.30) in children. PBR was not different from ELBW survivors during early adolescence, despite their higher blood pressure, lower eGFRcysC, and different retinal vessel width and tortuosity. We generated reference values for PBR in early adolescence. Despite some correlations between microvascular parameters, there seem to be numerous confounders to propose PBR as a marker for endothelial integrity in ELBW survivors. The endothelial glycocalyx is a complex and versatile structure. Changes in blood pressure and retinal and renal vascularization suggest a disturbance of its integrity in extremely low birth weight (ELBW) survivors. Its thickness can be measured by calculating perfused boundary region (PBR) using sidestream dark-field imaging, with a higher PBR indicating a thinner glycocalyx. We generated reference values for PBR in healthy adolescents. These values were not different in former ELBW children. Despite some correlations of PBR with other microvascular biomarkers, these are not strong enough to describe endothelial integrity and its covariates in former ELBW children.

Evaluation of the impact of blood donation on tissue perfusion and sublingual microcirculation in dogs: A pilot study

The objective was to assess the feasibility of the sublingual microcirculation evaluation in dogs by using Sidestream Dark Field (SDF) imaging device and to evaluate the impact of blood donation on sublingual microcirculation and tissue perfusion. Before and after blood sampling, macrocirculatory parameters and tissue perfusion parameters were collected. After quality assessment, four videos per individual and per period were retained for analysis. Data were presented as median (1st quartile – 3rd quartile).The evaluation of the sublingual microcirculation with SDF was feasible in sedated dogs: good quality videos could be recorded in 10/12 dogs (83%). The median blood donation volume was 14 mL/kg (13–15). A significant association between the volume of blood collected and the increase in heart rate was observed: for each milliliter of blood drawn, heart rate increased by 1 bpm (CI95% = [0.2, 2], P = 0.03). Blood collection was associated with a significant increase of shock index (estimate = 0.17, CI95% = [0.02, 0.32], P = 0.04). After blood donation, lactate concentration significantly decreased (before: 2.1 (1.7–2.8), after: 1.1 (0.8–1.7) mmol/l, P = 0.009). No significant variation of the microcirculatory parameters was observed.In conclusion, sublingual evaluation of the microcirculation with SDF technology is feasible in dogs. In the present condition, blood donation did not significantly alter microcirculation. These results need to be confirmed in a larger population.