Microvascular rarefaction in patients with cerebrovascular events.

Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n = 13 ischemic, n = 1 ischemic with hemorrhagic transformation and n = 2 hemorrhagic stroke) or transitory ischemic attacks (n = 5) within 24 h after hospital admission and compared to an age- and sex-matched control group. Repetitive measurements were performed on the third day and after one week. Functional and perfused total capillary density was rarefied in the overall patient group (3060 vs 3717 µm/mm2, p = 0.001 and 5263 vs 6550 µm/mm2, p = 0.002, respectively) and in patients with ischemic strokes (2897 vs. 3717 µm/mm2, p < 0.001 and 5263 vs. 6550 µm/mm2, p = 0.006, respectively) when compared to healthy controls. The perfused boundary region (PBR), which was measured as an inverse indicator of glycocalyx thickness, was markedly related to red blood cell (RBC) filling percentage (regarded as an estimate of microvessel perfusion) in the overall patient group (r = -0.843, p < 0.001), in patients with ischemic strokes (r = -0.82, p = 0.001) as well as in healthy volunteers (r = -0.845, p < 0.001). In addition, there were significant associations between platelet count or platelet aggregation values (as measured by whole blood impedance aggregometry) and microvascular parameters in the overall patient collective, as well as in patients with ischemic strokes. In conclusion, cerebrovascular events are associated with altered systemic microvascular perfusion.

Effects of a single aerobic exercise on perfused boundary region and microvascular perfusion: a field study.

The endothelium and the glycocalyx play a pivotal role in regulating microvascular function and perfusion in health and critical illness. It is unknown today, whether aerobic exercise immediately affects dimensions of the endothelial surface layer (ESL) in relation to microvascular perfusion as a physiologic adaption to increased nutritional demands. This monocentric observational study was designed to determine real-time ESL and perfusion measurements of the sublingual microcirculation using sidestream dark field imaging performed in 14 healthy subjects before and after completing a 10 km trial running distance. A novel image acquisition and analysis software automatically analysed the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration of the ESL, in vessels between 5 and 25 µm diameter. Microvascular perfusion was assessed by calculating RBC filling percentage. There was no significant immediate effect of exercise on PBR and RBC filling percentage. Linear regression analysis revealed a distinct association between change of PBR and change of RBC filling percentage (regression coefficient ß: - 0.026; 95% confidence interval - 0.043 to - 0.009; p = 0.006). A single aerobic exercise did not induce a change of PBR or RBC filling percentage. The endothelium of the microvasculature facilitates efficient perfusion in vessels reacting with an increased endothelial surface layer.

Endothelial glycocalyx damage in kidney disease correlates with uraemic toxins and endothelial dysfunction.

BACKGROUND: Damage to the endothelial glycocalyx is an early indicator of vascular damage and a potential marker of endothelial dysfunction. This study aimed to assess the relationship between markers of glycocalyx damage, endothelial dysfunction, and uraemic toxins in patients with chronic kidney disease. METHODS: Healthy controls, CKD patients, dialysis patients, and kidney transplant recipients had biochemical markers of glycocalyx damage (syndecan-1 and hyaluronan), endothelial dysfunction (von Willebrand factor; vWF and vascular cell adhesion molecule; VCAM-1), and uraemic toxins (indoxyl sulphate and p-cresyl sulphate) measured. In addition, Sidestream Darkfield imaging was performed using the novel GlycoCheck™ device to measure glycocalyx width by the perfused boundary region (PBR) in the sublingual microcirculation. RESULTS: Serum markers of glycocalyx damage were highest in the dialysis group (n = 33), followed by CKD patients (n = 32) and kidney transplant recipients (n = 30) compared to controls (n = 30): hyaluronan: 137 (16-1414), 79 (11-257), 57 (14-218) and 23 (8-116) ng/mL, respectively, p < 0.0001; syndecan-1: 81 (40-529), 46 (21-134), 39 (23-72), and 30 (12-138) ng/mL, respectively, p < 0.0001. Markers of endothelial dysfunction followed a similar pattern. No difference in the width of the PBR was detected between these groups (2.01 ± 0.35, 2.07 ± 0.27, 2.06 ± 0.28, and 2.05 ± 0.3 µm, respectively, p = 0.89). Glycocalyx damage correlated with markers of endothelial dysfunction (log-hyaluronan and log-VCAM-1: r = 0.64, p < 0.001) and levels of uraemic toxins (log-hyaluronan and log-indoxyl sulphate: r = 0.48, p < 0.001). CONCLUSIONS: Levels of biochemical markers of glycocalyx and endothelial cell damage are highest in patients receiving dialysis. Glycocalyx and endothelial damage markers correlated with each other, and with uraemic toxins. Although we could not demonstrate a change in PBR, the biochemical markers suggest that glycocalyx damage is most marked in patients with higher levels of uraemic toxins.

Can sidestream dark field (SDF) imaging identify subtle microvascular changes of the bowel during colorectal surgery?

BACKGROUND: Recognition of a non-viable bowel during colorectal surgery is a challenging task for surgeons. Identifying the turning point in serosal microcirculatory deterioration leading up to a non-viable bowel is crucial. The aim of the present study was to determine whether sidestream darkfield (SDF) imaging can detect subtle changes in serosal microcirculation of the sigmoid after vascular transection during colorectal surgery. METHODS: A prospective observational clinical study was performed at a single medical centre. All eligible participants underwent laparoscopic sigmoid resection and measurements were taken during the extra-abdominal phase. Microcirculation was measured at the transected bowel and 20 cm proximal to this point. Microcirculatory parameters such as Microvascular Flow Index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD), total vessel density (TVD) and the Heterogeneity Index were determined. Data are presented as median (interquartile range) or mean ± standard deviation. RESULTS: A total of 60 SDF images were acquired for 10 patients. Perfusion parameters and perfused vessel density were significantly lower at the transected bowel compared with the non-transected measurements [MFI 2.29 (1.96-2.63) vs 2.96 (2.73-3.00), p = 0.007; PPV 74% (55-83) vs 94% (86-97), p = 0.007; and PVD 7.61 ± 2.99 mm/mm2 versus 10.67 ± 1.48 mm/mm2, p = 0.009]. Total vessel density was similar between the measurement locations. CONCLUSIONS: SDF imaging can identify changes of the bowel serosal microcirculation. Significantly lower serosal microcirculatory parameters of the vascular transected bowel was seen compared with the non-transected bowel. The ability of SDF imaging to detect subtle differences holds promise for future research on microvascular cut-off values leading to a non-viable bowel.

Papaverine improves sublingual blood flow in patients with septic shock.

BACKGROUND: In recent years, microcirculatory blood flow alterations have been recognized to be stronger predictors of septic shock treatment outcomes than global hemodynamic variables. METHODS: In our self-controlled, interventional pilot clinical trial study, we investigated the effects of a single papaverine injection on the microcirculation in sepsis patients undergoing fluid resuscitation combined with vasopressor treatments. Fourteen septic shock patients admitted to the Peking University Third Hospital were included in the study, and each patient received 30 mg papaverine, which is the approximate dosage used to treat a conventional arterial spasm. Papaverine was administered as an intravenous bolus injection after systemic hemodynamic stabilization had been achieved by means of fluid resuscitation combined with dopamine and/or norepinephrine vasopressor medication. Baseline characteristics, as well as global hemodynamic and blood gas parameters, before and 60 min after papaverine injection were recorded and sublingual microcirculatory data at baseline and 15, 30, and 60 min after papaverine administration obtained using sidestream dark-field video microscopy. RESULTS: The perfused vessel density of small vessels was significantly increased 30 and 60 min after papaverine administration (P < 0.01), and the proportion of perfused small vessels (PPV), as well as the microvascular flow index, was significantly increased 30 min after papaverine (P < 0.05). There were no visible systemic effects, arrhythmia, or hypotension during the observation period in each patient. CONCLUSIONS: In our pilot study, papaverine transiently improved sublingual microcirculatory blood flow without influencing systemic hemodynamics in patients with septic shock, who required vasoconstrictors to maintain blood pressure during fluid resuscitation.

Microcirculation changes during liver resection--a clinical study.

BACKGROUND: In this study we aimed to evaluate effects of liver resection on hepatic microcirculation. In addition we wanted to study if histological liver damage could be detected intra-operatively. PATIENTS AND METHODS: 40 patients undergoing hepatic resection were included and grouped according to if they were operated with a major or minor resection. Hepatic microcirculation measurements were made intra-operatively before and after liver resection with sidestream dark-field (SDF) imaging. Red blood cell velocity (RBCV), sinusoidal diameter and functional sinusoidal density were determined. RESULTS: After hepatic resection RBCV increased in both the minor and major groups (44 µm/s, P=0.016 and 121 µm/s, P=0.002). RBCV in patients with histological damages was 225 (148-464) µm/s vs. 161 (118-329) µm/s in patients with no damage (P=0.016). CONCLUSION: A hepatic resection leads to an increase of sinusoidal RBCV. SDF imaging could potentially be used to intraoperatively identify histological damages.

Increased arginase levels contribute to impaired perfusion after cardiopulmonary resuscitation.

OBJECTIVES: The postcardiac arrest syndrome occurs after global hypoxia leading to microcirculatory impairment. Nitric oxide (NO) is a key molecule regulating microvascular function. The enzyme arginase has been suggested to modulate microvascular function by regulating NO metabolism. Therefore, we investigated whether arginase increases following global hypoxia and resuscitation and tested whether arginase inhibition influences altered microcirculation in resuscitated patients. METHODS: To determine the effect of global hypoxia on circulating arginase levels, fourteen healthy subjects were exposed to hypoxia in a normobaric hypoxia chamber (FiO² = 9·9%). In addition, 31 resuscitated patients were characterized clinically, and arginase 1 was measured on days 1 and 3. In eight resuscitated patients, a microcirculatory analysis was performed using a sidestream darkfield microcirculation camera. Perfused capillary density (PCD) was recorded before and after sublingual incubation of N-omega-hydroxy-nor-l-arginine (nor-NOHA) alone or together with the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA). RESULTS: Circulating arginase 1 levels increased in healthy volunteers following global hypoxia in the hypoxic chamber (P < 0·01). In addition, arginase 1 levels were higher on day 1 (69·1 ± 83·3 ng/mL) and on day 3 (44·2 ± 65·6 ng/mL) after resuscitation than in control subjects (P < 0·001). Incubation of the sublingual mucosa with nor-NOHA increased microcirculatory perfusion (P < 0·001). This effect was inhibited by co-incubation with K-NMMA. CONCLUSIONS: Circulating arginase 1 levels are increased following exposure to global hypoxia and in patients who have been successfully resuscitated after cardiac arrest. Topical arginase inhibition improves microcirculatory perfusion following resuscitation. This is of potential therapeutic importance for the postcardiac arrest syndrome.

Microcirculation in women with severe pre-eclampsia and HELLP syndrome: a case-control study.

OBJECTIVE: To compare microcirculatory perfusion in women with severe pre-eclampsia against that in healthy pregnant women, and secondly in women with severe pre-eclampsia with or without HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets). DESIGN: Case-control study. SETTING: University Hospital Rotterdam, the Netherlands. POPULATION: Twenty-three women with severe pre-eclampsia and 23 healthy pregnant controls, matched for maternal and gestational age. Out of the 23 women with severe pre-eclampsia, ten presented with HELLP syndrome. METHODS: Microcirculation was analysed sublingually by a non-invasive sidestream dark-field imaging device (SDF). MAIN OUTCOME MEASURES: Perfused vessel density (PVD), microcirculatory flow index (MFI), and heterogeneity index (HI) were calculated for both small vessels (∅ < 20 µm; capillaries) and non-small vessels (∅ > 20 µm; venules and arterioles). RESULTS: There were no significant differences between women with severe pre-eclampsia and healthy controls. Women with pre-eclampsia and HELLP syndrome showed a reduced PVD (P = 0.045), MFI (P = 0.008), and increased HI (P = 0.002) for small vessels, as compared with women with pre-eclampsia but without HELLP syndrome. CONCLUSIONS: Sidestream dark-field is a novel, promising technique in obstetrics that permits the non-invasive evaluation of microcirculation. We did not observe major differences in sublingual microcirculatory perfusion between women with severe pre-eclampsia and healthy pregnant controls. In women with severe pre-eclampsia, the presence of HELLP syndrome is characterised by impaired capillary perfusion.

Comparison of sublingual microcirculatory parameters measured by sidestream darkfield videomicroscopy in anesthetized pigs and adult humans.

BACKGROUND: This study aimed to compare sublingual microcirculatory parameters between anesthetized pigs and conscious adult humans using sidestream darkfield videomicroscopy. The overarching aim of the work was to validate the pig as an experimental model of changes in microcirculatory function following traumatic haemorrhagic shock and resuscitation. METHODS: Fourteen large white pigs and 14 humans were recruited for the study. Sublingual sidestream darkfield videomicroscopy clips were captured in anesthetized pigs and conscious humans. Clips underwent manual analysis in Automated Vascular Analysis 3.2 software. The total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPVs) and microvascular flow index (MFI) were quantified. An independent samples t test was used for between species comparison of microcirculatory parameters. RESULTS AND CONCLUSIONS: Conscious humans had a significantly lower TVD, PVD and MFI than anesthetized pigs. No significant difference in PPVs was observed between the species. Perfusion of the microcirculation is a critical determinant of tissue metabolic function and viability. Whilst it may not be surprising that some interspecies differences in the sublingual microcirculatory anatomy were identified between pig and human subjects, it is interesting to report the insignificant difference in PPVs. This direct microcirculatory measure represents a relative change which should hold translatable value across species. We therefore conclude the pig is a suitable model for microcirculatory research and may be a suitable species to investigate changes in microcirculatory perfusion following perturbations in cardiovascular homeostasis, for example during traumatic haemorrhagic shock and resuscitation.

Assessment of the microvascular perfusion using sidestream dark-field imaging in healthy newborn foals.

BACKGROUND: Different methods to measure tissue perfusion are available in equine neonatology, but they are not representative of microvascular derangements. OBJECTIVE: To evaluate the feasibility of the sidestream dark-field (SDF) capillaroscopy to visualize the capillary microvasculature in conscious newborn foals, the differences between two imaging sites and times of measurements, and the measurements' reproducibility. METHODS: Seventeen healthy newborn foals were enrolled. Three sites at the upper and lower lip mucosa were assessed by SDF, using a hand-held capiscope, at 24 h and at 4-5 days after birth. Videos were assessed independently by two observers for quality and for semiquantitative calculation of microvascular parameters, including vascular density (VD), microvascular flow index (MFI), proportion of perfused vessels (PPV), and functional capillary density (FCD). Data were analyzed using unpaired and paired Student's T-tests to assess differences between sites and time-points. Bland-Altman plots and intraclass correlation coefficient (ICC) were used to assess measurement reproducibility. RESULTS: Differences were found between the upper and the lower lip for VD at both 24 h and 4-5 days, and for FCD at 24 h, and between the two time-points for PPV at the lower lip. ICC for measurement reproducibility was good for all parameters (0.64-0.79) for the lower lip, and was good for VD and FCD (0,76-0,79) and fair to moderate for MFI and PPV (0.31-0.41) for the upper lip. CONCLUSIONS: Measurement of the capillary microvasculature is feasible in the conscious newborn foal. The lower lip has the best measurement reproducibility. Further investigations are warranted in cardiovascularly compromised cases, particularly in septic foals.

Interobserver reliability for manual analysis of sidestream darkfield videomicroscopy clips after resizing in ImageJ.

BACKGROUND: Direct assessment of microcirculatory function remains a critical care research tool but approaches for analysis of microcirculatory videomicroscopy clips are shifting from manual to automated algorithms, with a view to clinical application in the intensive care unit. Automated analysis software associated with current sidestream darkfield videomicroscopy systems is demonstrably unreliable; therefore, semi-automated analysis of captured clips should be undertaken in older generations of software. We present a method for capture of microcirculatory clips using current version videomicroscope hardware and resizing of clips to allow compatibility with legacy analysis software. The interobserver reliability of this novel approach is examined, in addition to a comparison of this approach with the current generation of automated analysis software. RESULTS: Resizing microcirculatory clips did not significantly change image quality. Assessment of bias between observers for manual analysis of resized clips; and between manually analysed clips and automated software analysis was undertaken by Bland-Altman analysis. Bias was demonstrated for all parameters for manual analysis of resized clips (total vessel density = 6.8, perfused vessel density = 6.3, proportion of perfused vessels = - 8.79, microvascular flow index = - 0.08). Marked bias between manual analysis and automated analysis was also evident (total vessel density = 16.6, perfused vessel density = 16.0, proportion of perfused vessels = 1.8). The difference between manual and automated analysis was linearly related to the magnitude of the measured parameter. CONCLUSIONS: Poor reliability of automated analysis is a significant hurdle for clinical translation of microcirculatory monitoring. The method presented here allows capture of microcirculatory clips using current hardware that are backwards compatible with older versions of manual analysis software. We conclude that this approach is appropriate for research applications in the intensive care unit, however the time delay to results limits utility for clinical translation.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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/).

The endothelial glycocalyx in critical illness: A pediatric perspective.

The vascular endothelium is the interface between circulating blood and end organs and thus has a critical role in preserving organ function. The endothelium is lined by a glycan-rich glycocalyx that uniquely contributes to endothelial function through its regulation of leukocyte and platelet interactions with the vessel wall, vascular permeability, coagulation, and vasoreactivity. Degradation of the endothelial glycocalyx can thus promote vascular dysfunction, inflammation propagation, and organ injury. The endothelial glycocalyx and its role in vascular pathophysiology has gained increasing attention over the last decade. While studies characterizing vascular glycocalyx injury and its downstream consequences in a host of adult human diseases and in animal models has burgeoned, studies evaluating glycocalyx damage in pediatric diseases are relatively few. As children have unique physiology that differs from adults, significant knowledge gaps remain in our understanding of the causes and effects of endothelial glycocalyx disintegrity in pediatric critical illness. In this narrative literature overview, we offer a unique perspective on the role of the endothelial glycocalyx in pediatric critical illness, drawing from adult and preclinical data in addition to pediatric clinical experience to elucidate how marked derangement of the endothelial surface layer may contribute to aberrant vascular biology in children. By calling attention to this nascent field, we hope to increase research efforts to address important knowledge gaps in pediatric vascular biology that may inform the development of novel therapeutic strategies.

Quantitative change of perfusion in gastric tube reconstruction by sidestream dark field microscopy (SDF) after esophagectomy, a prospective in-vivo cohort study.

BACKGROUND: Anastomotic leakage is one of the most severe complications in patients undergoing esophagectomy with gastric tube reconstruction. Transection of the left gastric and gastro-epiploic artery and vein results in compromised perfusion which is seen as the major contributing factor for anastomotic dehiscence. The main objective of this prospective, observational, in-vivo pilot study is to microscopically evaluate gastric tube perfusion with Sidestream Darkfield Microscopy (SDF). METHODS: Intra-operative microscopic images of gastric-microcirculation were obtained with SDF directly after reconstruction in 22 patients. Quantitative perfusion related parameters were: velocity, Microvascular Flow Index(MFI), Total Vessel Density(TVD), Perfusion Vessel Density(PVD), Proportion of Perfused Vessels(PPV) and De Backer Score(DBS). Dedicated software was used to assess parameters predictive for compromised perfusion. RESULTS: SDF was feasible to accurately visualize and evaluate microcirculation in all patients. Velocity(µm/sec) was significantly decreased towards the fundus (p = 0.001). MFI, PVD and PVD were decreased distal of the watershed - between the right and left gastro-epiploic artery and vein - and in the fundus, compared to the base of the gastric tube(p = 0.0002). No differences in TVD and DBS were observed; because of vessel-dilation in the fundus-area. This suggests that venous congestion results in comprised inflow of oxygen rich blood and plays a role in the development of ischaemia. CONCLUSION: We present quantitative perfusion imaging with SDF of the gastric tube. Velocity, MFI, TVD and PPV are accurate parameters to observe perfusion decrease. Also, venous congestion is visible in the fundus, suggesting an important role in the development of ischaemia. These parameters could allow early risk stratification, and, potentially, can accomplish a reduction in anastomotic leakage.

Real-time visualization of renal microperfusion using laser speckle contrast imaging.

SIGNIFICANCE: Intraoperative parameters of renal cortical microperfusion (RCM) have been associated with postoperative ischemia/reperfusion injury. Laser speckle contrast imaging (LSCI) could provide valuable information in this regard with the advantage over the current standard of care of being a non-contact and full-field imaging technique. AIM: Our study aims to validate the use of LSCI for the visualization of RCM on ex vivo perfused human-sized porcine kidneys in various models of hemodynamic changes. APPROACH: A comparison was made between three renal perfusion measures: LSCI, the total arterial renal blood flow (RBF), and sidestream dark-field (SDF) imaging in different settings of ischemia/reperfusion. RESULTS: LSCI showed a good correlation with RBF for the reperfusion experiment (0.94 ± 0.02; p < 0.0001) and short- and long-lasting local ischemia (0.90 ± 0.03; p < 0.0001 and 0.81 ± 0.08; p < 0.0001, respectively). The correlation decreased for low flow situations due to RBF redistribution. The correlation between LSCI and SDF (0.81 ± 0.10; p < 0.0001) showed superiority over RBF (0.54 ± 0.22; p < 0.0001). CONCLUSIONS: LSCI is capable of imaging RCM with high spatial and temporal resolutions. It can instantaneously detect local perfusion deficits, which is not possible with the current standard of care. Further development of LSCI in transplant surgery could help with clinical decision making.

Alterations of cerebral microcirculation in peritumoral edema: feasibility of in vivo sidestream dark-field imaging in intracranial meningiomas.

BACKGROUND: Intracranial meningiomas display a variable amount of peritumoral brain edema (PTBE), which can significantly impact perioperative morbidity. The role of microcirculatory disturbances in the pathogenesis of PTBE is still debated. The aim of this study was to microscopically demonstrate and intraoperatively quantify, for the first time, the alterations to microcirculation in PTBE using sidestream dark-field (SDF) imaging. METHODS: Adult patients with WHO grade I meningiomas were recruited over a 9-month period and divided into 2 groups depending on the absence (NE group) or the presence (E group) of PTBE. In vivo intraoperative microcirculation imaging was performed in the peritumoral area before and after microsurgical resection. RESULTS: Six patients were included in the NE group and 6 in the E group. At the baseline in the NE group, there was a minor decrease in microcirculatory parameters compared to normal reference values, which was probably due to the mass effect. In contrast, microcirculatory parameters in the E group were significantly altered, affecting both vessel density and blood flow values, with a drop of approximately 50% of normal values. Surgical resection resulted in a quasi-normalization of microcirculation parameters in the NE group, whereas in the E group, even if all parameters statistically significantly improved, post-resection values remained considerably inferior to those of the normal reference pattern. CONCLUSION: Our study confirmed significant alterations of microcirculatory parameters in PTBE in meningiomas. Further in vivo SDF imaging studies may explore the possible correlation between the severity of these microcirculatory alterations and the postoperative neurological outcome.

Outcome of a rabbit model for late irradiation effects in mandibular oral mucosa and bone: A pilot study.

BACKGROUND/AIM/OBJECTIVE: Late side effects of radiotherapy (RT) in the treatment for head and neck (HN) malignancies involve an inadequate healing response of the distressed tissue due to RT-induced hypovascularity. The aim of this study was to develop a pilot model in which vascular alterations associated with the onset of late irradiation (IR) injury could be measured in rabbit oral mucosa and mandibular bone. MATERIALS AND METHODS: Eight male New Zealand white rabbits were divided over four treatment groups. Group I-III received four fractions of RT (5.6 Gy, 6.5 Gy, and 8 Gy, respectively) and Group IV received 1 fraction of 30 Gy. Oral microcirculatory measurements were performed at baseline (before RT) and once a week during 11 consecutive weeks after RT assessing perfusion parameters, that is, total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI). Post-mortem histopathology specimens were analyzed. RESULTS: Five weeks after RT, TVD, and PVD in all groups showed a decrease of >10% compared to baseline, a significant difference was observed for Groups I, II, and IV (P<0.05). At T11, no lasting effect of decreased vessel density was observed. PPV and MFI remained unaltered at all-time points. Group IV showed a marked difference in scattered telangiectasia such as microangiopathies, histological necrosis, and loss of vasculature. CONCLUSION: No significant lasting effect in mucosal microcirculation density due to IR damage was detected. Observed changes in microcirculation vasculature and histology may align preliminary tissue transition towards clinical pathology in a very early state associated with late IR injury in the oral compartment. RELEVANCE FOR PATIENTS: Enhancing knowledge on the onset of late vascular IR injury in the HN region could help the development, monitoring, and timing of therapies that act on prevention, discontinuation, or repair of radiation pathology.

Possible Impact of Spinal Anesthesia and Phenylephrine on Sublingual Microcirculation of Cesarean Delivery Patients.

BACKGROUND: This study was a proof of concept of a novel means to evaluate microcirculatory changes during spinal anesthesia for cesarean delivery. It sought to examine the distributive circulatory effects of spinal anesthesia and evaluate the impact of phenylephrine administration on the microcirculation of these women. METHODS: After Research Ethics Board approval, healthy, non-laboring pregnant women with singleton, term pregnancies scheduled for elective cesarean delivery were recruited. Participants were randomly assigned to receive either phenylephrine infusion or phenylephrine bolus. Spinal anesthesia was standardized. A sidestream dark-field (SDF) MicroScan® video microscope was applied to the sublingual mucosa to obtain microcirculation videos in five different visual fields. Videos were made before and after spinal anesthesia. The resultant videos were analyzed randomly and blindly. The mean microvascular flow index (MFI) values were compared before and after spinal anesthesia. The difference in MFI following spinal anesthesia was compared between phenylephrine infusion and bolus groups. RESULTS: Thirty-two patients were recruited for the study; 22 patients had complete video sets for analysis. Baseline characteristics were similar between the two groups, including preoperative hemodynamics. There were no significant differences between pre- and post-spinal MFI. The post-spinal MFI within the infusion group (mean ± standard deviation: 2.74 ± 0.21) was not significantly different from the bolus group (2.56 ± 0.42, P = 0.22). CONCLUSION: Despite theoretical physiological implications of spinal anesthesia and phenylephrine on the microcirculation, significant alteration of the MFI was not observed between pre- and post-spinal anesthesia (within group). Additionally, despite an eight-fold larger phenylephrine dose for continuous infusion prophylaxis used in this group of women, this did not result in a significant alteration of the microcirculation compared to those who received phenylephrine treatment for hypotension (between groups).

Two-wavelength oximetry of tissue microcirculation based on sidestream dark-field imaging.

Monitoring oxygen saturation (SO2) in microcirculation is effective for understanding disease dynamics. We have developed an SO2 estimation method, sidestream dark-field (SDF) oximetry, based on SDF imaging. SDF imaging is a noninvasive and clinically applicable technique to observe microcirculation. We report the first in vivo experiment observing the changes in SO2 of microcirculation using SDF oximetry. First, heat from the light-emitting diodes used for the SDF imaging might affect hemodynamics in microcirculation, hence, we performed an experiment to evaluate the influence of that on the SDF oximetry. The result suggested that SDF oximetry had enough stability for long-term experiments. Then, to evaluate the sensitivity of SDF oximetry to alterations in the hemodynamics of the microcirculation, we observed the time-lapsed SO2 changes in the dermis microcirculation of rats under hypoxic stimulation. We confirmed that the SO2 estimated by SDF oximetry was in accordance with changes in the fraction of inspired oxygen (FiO2). Thus, SDF oximetry is considered to be able to observe SO2 changes that occur in accordance with alteration of the microcirculation.