Sublingual microcirculatory assessment on admission independently predicts the outcome of old intensive care patients suffering from shock.

Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes.Trial registration NCT04169204.

The Usefulness of Microcirculatory Assessment After Cardiac Surgery: Illustrative Case Report.

Cardiac surgery causes a series of disturbances in human physiology. The correction of systemic hemodynamic variables is frequently ineffective in improving microcirculatory perfusion and delivering oxygen to the tissues. We present the case of a 52-year-old male submitted to mitral valve replacement (metallic valve) and subaortic membrane resection. Sublingual microcirculatory density and perfusion were evaluated using a handheld CytoCam camera before surgery and in the early postoperative period. In this case, systemic hemodynamic variables were compromised despite an actual improvement in the microcirculatory parameters in comparison to the preoperative evaluation, possibly due to the correction of the structural cardiac defects.

Sublingual microcirculatory alterations in Chagas disease: an observational study in an endemic rural population.

BACKGROUND: Chagas disease is a systemic illness with widespread microvascular involvement. Experimental and clinical studies suggest that functional and structural microcirculatory abnormalities might be relevant to the disease progression. OBJECTIVES: To show the presence of sublingual microcirculatory alterations in patients with chronic Chagas disease. METHODS: This was a cross-sectional study including adult patients with serologic diagnosis of Chagas disease (n = 41) and control volunteers with negative serology (n = 38), from an endemic rural population. Study participants underwent clinical, electrocardiographic, echocardiographic, and sublingual videomicroscopic assessment. Videos were acquired by a sidestream-dark-field (SDF) imaging device and evaluated by a software-assisted analysis (AVA 3.2 software). FINDINGS: Most of Chagas disease patients were in the indeterminate phase (n = 34) and had lower heart rate and more echocardiographic abnormalities than control group (50 vs. 26%, p = 0.03). They also exhibited higher small microvessels total and perfused vascular density (20.12 ± 2.33 vs. 19.05 ± 2.25 and 20.03 ± 2.28 vs. 19.01 ± 2.25 mm/mm2, p < 0.05 for both). Other microvascular variables did not differ between groups. MAIN CONCLUSIONS: Patients with chronic Chagas disease exhibited increases in sublingual total and perfused microvascular density. Angiogenesis might be the underlying mechanism. The videomicroscopic assessment of mucosal sublingual microcirculation might be an additional tool in the monitoring of Chagas disease.

Machine Learning-Assisted Analysis of Sublingual Microcirculatory Dysfunction for Early Cardiovascular Risk Evaluation and Cardiovascular-Kidney-Metabolic Syndrome Stage in Patients With Type 2 Diabetes Mellitus.

AIMS: To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points. RESULTS: Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA. CONCLUSIONS: Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.

Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.NEW & NOTEWORTHY To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation.

Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients.

BACKGROUND: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. METHODS: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. RESULTS: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 µm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). CONCLUSION: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.

Relationship between sublingual varices and hypertension: a systematic review and meta-analysis.

BACKGROUND: Previous research has investigated the connection between sublingual varices (SV) and cardiovascular disease, aging, and smoking. However, it is still unclear whether arterial hypertension affects the presence of SV. This meta-analysis aimed to investigate the relationship between hypertension and the presence of SV. METHODS: The literature search was performed using PubMed, Web of Science, Scopus, Google Scholar, and Embase for cross-sectional studies until July 2023. PRISMA guidelines were used for article selection. A meta-analysis using standardized mean differences by a random effects model was conducted to pool studies. RESULTS: A total of 568 articles were retrieved, of which twelve were included in the meta-analysis. Cumulatively, 2543 samples in the case group (1185 with hypertension) and 3897 samples (821 with hypertension) were studied in the control group. Using the random effects model, the pooled odds ratio (OR) revealed a significant association between hypertension and sublingual varices (OR = 2.66; 95% CI: 1.69-4.18). CONCLUSION: The meta-analysis showed a significant and positive association between sublingual varices and hypertension. SV's presence could be used by dentists as a non-invasive indicator of hypertension screening.

The microcirculation in perioperative medicine: a narrative review.

The microcirculation describes the network of the smallest vessels in our cardiovascular system. On a microcirculatory level, oxygen delivery is determined by the flow of oxygen-carrying red blood cells in a given single capillary (capillary red blood cell flow) and the density of the capillary network in a given tissue volume (capillary vessel density). Handheld vital videomicroscopy enables visualisation of the capillary bed on the surface of organs and tissues but currently is only used for research. Measurements are generally possible on all organ surfaces but are most often performed in the sublingual area. In patients presenting for elective surgery, the sublingual microcirculation is usually intact and functional. Induction of general anaesthesia slightly decreases capillary red blood cell flow and increases capillary vessel density. During elective, even major, noncardiac surgery, the sublingual microcirculation is preserved and remains functional, presumably because elective noncardiac surgery is scheduled trauma and haemodynamic alterations are immediately treated by anaesthesiologists, usually restoring the macrocirculation before the microcirculation is substantially impaired. Additionally, surgery is regional trauma and thus likely causes regional, rather than systemic, impairment of the microcirculation. Whether or not the sublingual microcirculation is impaired after noncardiac surgery remains a subject of ongoing research. Similarly, it remains unclear if cardiac surgery, especially with cardiopulmonary bypass, impairs the sublingual microcirculation. The effects of therapeutic interventions specifically targeting the microcirculation remain to be elucidated and tested. Future research should focus on further improving microcirculation monitoring methods and investigating how regional microcirculation monitoring can inform clinical decision-making and treatment.

Cross-sectional study of sublingual varicosities: systemic exposures.

PURPOSE: Sublingual varicose veins are a common vascular lesion with different names, such as caviar tongue or vascular malformations. This study aimed to investigate whether there is an association between sublingual varicose veins and cardiovascular diseases by observing arterial hypertension, diabetes, thrombosis, and infarction. In addition, to evaluate a series of thrombi that affected the oral cavity and to analyze their clinical aspects and relate them to possible systemic alterations. METHODS: This is a cross-sectional study consisting of a sample of 134 varicosities, 23 vascular malformations, and 4 thrombosis. RESULTS: Lingual varicosities are more frequently observed in women aged 57.4 ± 16.4 years. Hypertension was present in lingual varicosities (n = 73), as well as diabetes (n = 107), reports of thrombosis (n = 41), and infarction (n = 45). Arterial hypertension was decompensated (n = 12). The most frequent underlying diseases were diabetes (p < 0.001), infarction (p = 0.012), and thrombosis (p = 0.004), and the most commonly used drug was losartan. CONCLUSION: It can be inferred from the present study that lingual varicosities are related to cardiovascular diseases and can serve as a parameter to measure their decompensation.

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.

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.

The sublingual microcirculation and frailty index in chronic kidney disease patients.

OBJECTIVE: To examine the relationship between sublingual microcirculatory measures and frailty index in those attending a kidney transplant assessment clinic. METHODS: Patients recruited had their sublingual microcirculation taken using sidestream dark field videomicroscopy (MicroScan, Micro Vision Medical, Amsterdam, the Netherlands) and their frailty index score using a validated short form via interview. RESULTS: A total of 44 patients were recruited with two being excluded due to microcirculatory image quality scores exceeding 10. The frailty index score indicated significant correlations with total vessel density (p < .0001, r = -.56), microvascular flow index (p = .004, r = -.43), portion of perfused vessels (p = .0004, r = -.52), heterogeneity index (p = .015, r = .32), and perfused vessel density (p < .0001, r = -.66). No correlation was shown between the frailty index and age (p = .08, r = .27). CONCLUSIONS: There is a relationship between the frailty index and microcirculatory health in those attending a kidney transplant assessment clinic, that is not confounded by age. These findings suggest that the impaired microcirculation may be an underlying cause of frailty.

Association of Sublingual Microcirculation Parameters and Capillary Refill Time in the Early Phase of ICU Admission.

OBJECTIVES: This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow alteration and outcome in critically ill patients. DESIGN: Prospective, observational, pilot study. SETTING: ICU in a university hospital. PATIENTS: Two hundred eighty-two critically ill adult patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent simultaneous measurements by CRT and sidestream dark field imaging within 24 hours of ICU admission. Other clinical data such as demographic characteristics, hemodynamics, laboratory values, treatment, and physiologic parameters were also included simultaneously. Microcirculatory measurements were performed at 10.2 ± 5.7 hours after ICU admission. Of the 282 included patients, 106 (37.6%) were female, the median (interquartile range) age was 63 years (53-74 yr), and the median Sequential Organ Failure Assessment (SOFA) score was 5 (2-7). The primary finding was the association between CRT and simultaneous the condition of peripheral circulation (microvascular flow index [MFI]: r = -0.4430, p < 0.001; proportion of perfused vessels: r = -0.3708, p < 0.001; heterogeneity index: r = 0.4378, p < 0.001; perfused vessel density: r = -0.1835, p = 0.0020; except total vessel density: p = 0.9641; and De Backer score: p = 0.5202) in critically ill patients. In addition, this relationship was also maintained in subgroups. Microcirculatory flow abnormalities, 28-day mortality, and SOFA score appeared to be more severe for increasing CRT. In a multivariable analysis, prolonged CRT was independently associated with microvascular flow abnormalities (MFI < 2.6; odds ratio [OR], 1.608; 95% CI, 2.1-10.2; p < 0.001). Similarly, multivariable analysis identified CRT as an independent predictor of 28-day mortality (OR, 1.296; 95% CI, 1.078-1.558; p = 0.006). CONCLUSIONS: In our ICU population, a single-spot prolonged CRT was independently associated with abnormal microcirculation and increased mortality.

Identifying a sublingual triangle as the ideal site for assessment of sublingual microcirculation.

The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm2 (p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm2 (p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm2 (p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters.

EFFECTS OF SHENFU INJECTION ON SUBLINGUAL MICROCIRCULATION IN SEPTIC SHOCK PATIENTS: A RANDOMIZED CONTROLLED TRIAL.

ABSTRACT: Background and Objective: The optimization of macrocirculatory hemodynamics is recommended by current sepsis guidelines. However, microcirculatory dysfunction is considered the cause of severe sepsis. In the present study, we designed to verify whether the application of Shenfu injection (SFI) restores microcirculation, thereby improving tissue perfusion and inhibiting organ dysfunction, resulting in improved outcomes. Design: We conducted a prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Intervention: Patients were randomly assigned to group receiving SFI (n = 20) or placebo (n = 20) for 5 days. We administered SFI or glucose injection for 5 days and blinded the investigators and clinical staff by applying light-proof infusion equipment that concealed therapy allocation. Measurements and Results: We measured the systemic dynamics and lactate levels, biomarkers of endothelial dysfunction, and inflammatory cytokines in the plasma. The parameters of sublingual microcirculation were assessed using side-stream dark-field imaging. Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) score, total dose, and duration of vasopressor use, emergency intensive care unit (EICU) stay, and 28-day mortality were evaluated. After treatment with SFI, the disturbance of the sublingual microcirculation was considerably alleviated, as indicated by the significant increase in total vessel density, perfused vessel density, and microvascular flow index. Moreover, the plasma biomarker levels of endothelial dysfunction, including Ang-2, Syn-1, and ET-1, were reversed after SFI treatment. Importantly, the SFI group had a more favorable prognosis than the control group in terms of the APACHE-II score, SOFA score, duration of vasopressor administration, and length of EICU stay. However, the difference in mortality at day 28 was not statistically different between the SFI (15%, 3/20) and placebo (25%, 5/20) groups ( P = 0.693). Conclusions : Shenfu injection provided apparent effects in improving sublingual microcirculatory perfusion in patients with septic shock, and this protection may be related with the inhibition of endothelial dysfunction and vasodilatory effects.

Evaluation of pimobendan effect on sublingual microcirculation in an experimental pharmacology induced hypotension porcine model.

New therapeutic approaches are needed to simultaneously resuscitate macro- and microcirculation during circulatory shock. The aims of this study were to explore the microcirculatory and macrocirculatory effects of pimobendan, an inodilator with dual phosphodiesterase 3 inhibitor and calcium-sensitizing effects, in an experimental porcine model of pharmacologically induced hypotension associating vasoplegia and decreased cardiac output. Eight piglets were anesthetized and monitored for their hemodynamic parameters. Hypotension was induced by sevoflurane overdose until a mean arterial pressure between 40 and 45 mmHg was reached. A bolus of pimobendan (0.25 mg/kg) was administered intravenously thereafter. Sublingual microcirculation was evaluated using a Sidestream Dark Field imaging device. Hemodynamic and microcirculatory parameters were recorded at the baseline period (A), immediately before pimobendan administration (B) and after pimobendan administration (C). Induction of hypotension was associated with a decreased cardiac index and microcirculation alterations. Pimobendan administration was associated with a significant increase in heart rate, cardiac index and decrease in systemic vascular resistance index. A significant increase in proportion of perfused vessels for all vessels (+8%, [2; 14], P = 0.01) and small vessels (+8% [1; 14], P = 0.03), in microvascular flow index (+0.31 AU, [0.04; 0,58], P = 0.03) were noticed, as well as a decrease in heterogeneity index (-0.34 [-0.66; -0.03], P = 0.04) and De Backer score for all vessels (-1.04, [-1.82; -0.25], P = 0.02). In conclusion, in a simple model of pharmacologically induced hypotension, pimobendan was associated with an improvement in several microcirculatory parameters.

Morphologic Mapping of the Sublingual Microcirculation in Healthy Volunteers.

PURPOSE: Monitoring the sublingual and oral microcirculation (SM-OM) using hand-held vital microscopes (HVMs) has provided valuable insight into the (patho)physiology of diseases. However, the microvascular anatomy in a healthy population has not been adequately described yet. METHODS: Incident dark field-based HVM imaging was used to visualize the SM-OM. First, the SM was divided into four different fields; Field-a (between incisors-lingua), Field-b (between the canine-first premolar-lingua), Field-c (between the first-second premolar-lingua), Field-d (between the second molar-wisdom teeth-lingua). Second, we investigated the buccal area, lower and upper lip. Total/functional vessel density (TVD/FCD), focus depth (FD), small vessel mean diameters (SVMDs), and capillary tortuosity score (CTS) were compared between the areas. RESULTS: Fifteen volunteers with a mean age of 29 ± 6 years were enrolled. No statistical difference was found between the sublingual fields in terms of TVD (p = 0.30), FCD (p = 0.38), and FD (p = 0.09). SVMD was similar in Field-a, Field-b, and Field-c (p = 0.20-0.30), and larger in Field-d (p < 0.01, p = 0.015). The CTS of the buccal area was higher than in the lips. CONCLUSION: The sublingual area has a homogenous distribution in TVD, FCD, FD, and SVMD. This study can be a description of the normal microvascular anatomy for future researches regarding microcirculatory assessment.

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.

Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study.

BACKGROUND: The availability of handheld, noninvasive sublingual video-microscopes allows for visualization of the microcirculation in critically ill patients. Recent studies demonstrate that reduced numbers of blood-perfused microvessels and increased penetration of erythrocytes into the endothelial glycocalyx are essential components of microvascular dysfunction. The aim of this study was to identify novel microvascular variables to determine the level of microvascular dysfunction in sepsis and its relationship with clinical variables. METHODS: This observational, prospective, cross-sectional study included 51 participants, of which 34 critically ill sepsis patients were recruited from intensive care units of a university hospital. Seventeen healthy volunteers served as controls. All participants underwent sublingual videomicroscopy by sidestream darkfield imaging. A new developed version of the Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell (RBC) velocity, RBC content, and blood flow in sublingual microvessels with diameters between 4 and 25 µm. RESULTS: A detailed analysis of adjacent diameter classes (1 µm each) of vessels between 4 and 25 µm revealed a severe reduction of vascular density in very small capillaries (5-7 µm), which correlated with markers of sepsis severity. Analysis of RBC velocity (VRBC) revealed a strong dependency between capillary and feed vessel VRBC in sepsis patients (R2 = 0.63, p < 0.0001) but not in healthy controls (R2 = 0.04, p = 0.43), indicating impaired capillary (de-)recruitment in sepsis. This finding enabled the calculation of capillary recruitment and dynamic capillary blood volume (CBVdynamic). Moreover, adjustment of PBR to feed vessel VRBC further improved discrimination between sepsis patients and controls by about 50%. By combining these dynamic microvascular and glycocalyx variables, we developed the microvascular health score (MVHSdynamic™), which decreased from 7.4 [4.6-8.7] in controls to 1.8 [1.4-2.7] in sepsis patients (p < 0.0001) and correlated with sepsis severity. CONCLUSION: We introduce new important diameter-specific quantification and differentiated analysis of RBC kinetics, a key to understand microvascular dysfunction in sepsis. MVHSdynamic, which has a broad bandwidth to detect microvascular (dys-) function, might serve as a valuable tool to detect microvascular impairment in critically ill patients.