Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications.

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p=0.044) and heart (p=0.001) components at the M1 and M5 regions (p=0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p=0.049) and myogenic (p=0.032) components at the M1 region, as well as in the endothelial (p<0.001) component at the M5 region and in the myogenic component at the dorsal foot (p=0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region (p=0.050) and heel area (p=0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p=0.017) and heel area (p=0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

[Optical coherence tomography angiography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike rasseyannogo skleroza.

PURPOSE: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course. MATERIAL AND METHODS: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA). RESULTS: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm2, wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05). CONCLUSION: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

Myofascial release induces declines in heart rate and changes to microvascular reactivity in young healthy adults.

OBJECTIVES: The purpose of this study was to compare physiological responses to myofascial release (MFR) and passive limb movement (PLM). DESIGN: Nineteen (23 ± 2.6yrs) adults (10 men and 9 women) completed two experiments on separate days: MFR and PLM. Participation included collecting ultrasound images, blood pressure, and heart rate (HR) as well as performing a vascular occlusion test (VOT). The VOT assessed muscle tissue oxygenation (StO2) with near-infrared spectroscopy. Experiments consisted of moving the upper limb to release subtle barriers of resistance in the muscle/fascia (MFR) and passive, assisted range of motion (PLM). RESULTS: There was a significantly (p = 0.012) greater decrease in HR following MFR (-7.3 ± 5.2 BPM) than PLM (-1.3 ± 0.9 BPM). There was an equivalent change in brachial blood flow (-17.3 ± 23.0 vs. -11.9 ± 14.9 mL min-1; p = 0.37) and vascular conductance (-19.3 ± 31.1 vs. -12.4 ± 15.3 mL min-1 mmHg-1; p = 0.38). Microvascular responses differed between the experiments such that MFR exhibited greater area under the curve (AUC, 1503 ± 499.1%∙s-1 vs. 1203 ± 411.1%∙s-1; p = 0.021) and time to maximum StO2 (40.0 ± 8.4s vs. 35.8 ± 7.3s; p = 0.009). CONCLUSIONS: As evidenced by HR, MFR induced greater parasympathetic activity than PLM. The greater AUC and time to StO2max following MFR suggested a spillover effect to induce prolonged hyper-saturation. These results may be of interest to those investigating possible MFR-related rehabilitative benefits.

Coronary microvascular dysfunction and atrial reservoir function.

BACKGROUND: Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr. METHODS: Consecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively. RESULTS: Forty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78-0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD. CONCLUSION: Patients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.

[Laser Doppler flowmetry in the diagnosis of chronic mixed blepharitis]. / Lazernaya dopplerovskaya floumetriya v diagnostike khronicheskogo smeshannogo blefarita.

Chronic mixed blepharitis accounts for 51.7% of all ophthalmic diseases. The use of laser Doppler flowmetry (LDF) in the diagnosis of this disease can help establish the initial manifestations of the inflammatory process in the eyelids, which is important for the prevention of possible complications - dry eye disease. PURPOSE: This study was conducted to determine the sensitivity and specificity of the LDF method in the diagnosis of chronic mixed blepharitis based on the study of microcirculatory changes in the eyelid skin. MATERIAL AND METHODS: The study included 23 patients with chronic mixed blepharitis (mean age 67±5.8 years) and 18 healthy volunteers (mean age 63±1.1 years). LDF was performed using the LAZMA MC-1 device. ROC analysis was used to determine sensitivity and specificity. RESULTS: A typical disturbance of the eyelid skin microcirculation was revealed in chronic mixed blepharitis - ischemia - with inhibition of the intensity of the functioning of blood flow regulatory systems and moderate activation of the lymph flow. The sensitivity and specificity of the coefficient of variation (reflecting the vasomotor activity of microvessels) of blood flow was 71.43 and 71.43%, lymph flow - 65.71 and 80.00%; myogenic rhythms of blood flow - 83.33 and 85.71%, lymph flow - 66.67 and 71.43%; neurogenic rhythms of blood flow - 75.00 and 78.57%, lymph flow - 91.67 and 78.57%, respectively. CONCLUSION: Laser Doppler flowmetry of the eyelid skin in combination with clinical, functional and instrumental research methods helped reveal with high sensitivity and specificity the eyelid damage in chronic mixed blepharitis. This method allows assessment of the condition of the eyelids in individuals without diseases of the anterior segment of the eye.

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

Retinal microcirculation: A window into systemic circulation and metabolic disease.

The retinal microcirculation system constitutes a unique terminal vessel bed of the systemic circulation, and its perfusion status is directly associated with the neural function of the retina. This vascular network, essential for nourishing various layers of the retina, comprises two primary microcirculation systems: the retinal microcirculation and the choroidal microcirculation, with each system supplying blood to distinct retinal layers and maintaining the associated neural function. The blood flow of those capillaries is regulated via different mechanisms. However, a range of internal and external factors can disrupt the normal architecture and blood flow within the retinal microcirculation, leading to several retinal pathologies, including diabetic retinopathy, macular edema, and vascular occlusions. Metabolic disturbances such as hyperglycemia, hypertension, and dyslipidemia are known to modify retinal microcirculation through various pathways. These alterations are observable in chronic metabolic conditions like diabetes, coronary artery disease, and cerebral microvascular disease due to advances in non-invasive or minimally invasive retinal imaging techniques. Thus, examination of the retinal microcirculation can provide insights into the progression of numerous chronic metabolic disorders. This review discusses the anatomy, physiology and pathophysiology of the retinal microvascular system, with a particular emphasis on the connections between retinal microcirculation and systemic circulation in both healthy states and in the context of prevalent chronic metabolic diseases.

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. METHODS AND RESULTS: This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CONCLUSIONS: CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

Coronary Microvascular Function Following Severe Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.

A New Approach to Vascular Screening: Identification of Impaired Vascular Function Using the FMSF Technique.

Arterial blood pressure monitoring plays an important role in preventive medicine, allowing, in selected cases, the identification of vascular dysfunction. In this review, we propose a new non-invasive approach to assessment of the circulatory system, based on its reaction to hypoxia induced by post-occlusive reactive hyperemia (PORH). Three key parameters can be used for vascular screening: the Reactive Hyperemia Response (RHR), which represents the overall reaction of the macro- and microcirculation to transient hypoxia; Hypoxia Sensitivity (HS), which reflects hypoxia-induced activation of myogenic oscillations of the microcirculation; and Normoxia Oscillatory Index (NOI), which characterizes microcirculatory oscillations under normoxia conditions. A method for assessing these parameters, analogous in simplicity to arterial blood pressure measurement, is provided by the Flow Mediated Skin Fluorescence (FMSF) technique. Reference values are proposed based on numerous test measurements.

Evaluation of Optic Nerve Head Microcirculation in Open-Angle Glaucoma Patients with Unilateral Visual Field Defect.

INTRODUCTION: Microcirculation of optic nerve head (ONH) in open-angle glaucoma (OAG) patients with unilateral visual field (VF) loss has yet to be fully investigated, especially the perimetrically unaffected fellow eyes. METHODS: Thirty-eight OAG patients with VF defect in one eye and normal VF in the other eye, and thirty-one healthy participants were analyzed. All participants underwent laser speckle flowgraphy (LSFG), spectral-domain optical coherence tomography (SD-OCT) imaging, and VF test for further analyses. LSFG measurements included mean blur rate in all area of ONH (MA), big vessel area of ONH (MV), and tissue area of ONH (MT). SD-OCT parameters included circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macula thicknesses. The difference of LSFG and SD-OCT indices between glaucoma patients and healthy controls were compared. The diagnostic accuracy was analyzed with the areas under the receiver operating characteristic curves (AROCs). RESULTS: Global cpRNFL thickness and macular thickness in unaffected eyes of OAG patients were higher than their fellow eyes and lower than healthy eyes. MA and MV in healthy eyes and unaffected eyes were significantly higher than in affected eyes. MT in unaffected eyes of OAG patients was higher than in their fellow affected eyes but lower than in healthy eyes. The AROCs were highest for cpRNFL (0.925), followed by macular thickness (0.838), and MT (0.834). CONCLUSIONS: ONH microcirculation in perimetrically unaffected fellow eyes was decreased in OAG patients with unilateral VF loss. LSFG can detect changes of ONH in high-risk eyes before detectable VF damage, which may reflect the vascular pathophysiology for glaucoma.

Resuscitating the macro- vs. microcirculation in septic shock.

PURPOSE OF REVIEW: This review summarizes current literature about the relationships between macro and microcirculation and their practical clinical implications in children with septic shock. RECENT FINDINGS: Current evidence from experimental and clinical observational studies in children and adults with septic shock reveals that the response to treatment and resuscitation is widely variable. Furthermore, there is a loss of hemodynamic coherence, as resuscitation-induced improvement in macrocirculation (systemic hemodynamic parameters) does not necessarily result in a parallel improvement in the microcirculation. Therefore, patient-tailored monitoring is essential in order to adjust treatment requirements during resuscitation in septic shock. Optimal monitoring must integrate macrocirculation (heart rate, blood pressure, cardiac output, and ultrasound images), microcirculation (videomicroscopy parameters and capillary refill time) and cellular metabolism (lactic acid, central venous blood oxygen saturation, and difference of central venous to arterial carbon dioxide partial pressure). SUMMARY: There is a dire need for high-quality studies to assess the relationships between macrocirculation, microcirculation and tissue metabolism in children with septic shock. The development of reliable and readily available microcirculation and tissue perfusion biomarkers (other than lactic acid) is also necessary to improve monitoring and treatment adjustment in such patients.

Age and sex differences in microvascular responses during reactive hyperaemia.

Microvascular impairments are typical of several cardiovascular diseases. Near-infrared spectroscopy (NIRS) combined with a vascular occlusion test provides non-invasive insights into microvascular responses by monitoring skeletal muscle oxygenation changes during reactive hyperaemia. Despite increasing interest in the effects of sex and ageing on microvascular responses, evidence remains inconsistent. Therefore, the present study aimed to investigate the effects of sex and age on microvascular responsiveness. Twenty-seven participants (seven young men and seven young women; seven older men and six older women; aged 26 ± 1, 26 ± 4, 67 ± 3 and 69 ± 4 years, respectively) completed a vascular occlusion test consisting of 5 min of arterial occlusion followed by 5 min reperfusion. Oxygenation changes in the vastus lateralis were monitored by near-infrared spectroscopy. The findings revealed that both women (referring to young and older women) and older participants (referring to both men and women) exhibited lower microvascular responsiveness. Notably, both women and older participants demonstrated reduced desaturation (-38% and -59%, respectively) and reperfusion rates (-24% and -40%, respectively) along with a narrower range of tissue oxygenation (-39% and -39%, respectively) and higher minimal tissue oxygenation levels (+34% and +21%, respectively). Women additionally displayed higher values in resting (+12%) and time-to-peak (+15%) tissue oxygenation levels. In conclusion, this study confirmed decreased microvascular responses in women and older individuals. These results emphasize the importance of considering sex and age when studying microvascular responses. Further research is needed to uncover the underlying mechanisms and clinical relevance of these findings, enabling the development of tailored strategies for preserving vascular health in diverse populations.

Mechanisms of coronary sinus reducer for treatment of myocardial ischemia: in silico study.

The coronary sinus reducer (CSR) is an emerging medical device for treating patients with refractory angina, often associated with myocardial ischemia. Patients implanted with CSR have shown positive outcomes, but the underlying mechanisms are unclear. This study sought to understand the mechanisms of CSR by investigating its effects on coronary microcirculation hemodynamics that may help explain the therapy's efficacy. We applied a validated computer model of the coronary microcirculation to investigate how CSR affects hemodynamics under different degrees of coronary artery stenosis. With moderate coronary stenosis, an increase in capillary transit time (CTT) [up to 69% with near-complete coronary sinus (CS) occlusion] is the key change associated with CSR. Because capillaries in the microcirculation can still receive oxygenated blood from the upstream artery with moderate stenosis, the increase in CTT allows more time for the exchange of gases and nutrients, aiding tissue oxygenation. With severe coronary stenosis; however, the redistribution of blood draining from the nonischemic region to the ischemic region (up to 96% with near-complete CS occlusion) and the reduction in capillary flow heterogeneity are the key changes associated with CSR. Because blood draining from the nonischemic region is not completely devoid of O2, the redistribution of blood to the capillaries in the ischemic region by CSR is beneficial especially when little or no oxygenated blood reaches these capillaries. This simulation study provides insights into the mechanisms of CSR in improving clinical symptoms. The mechanisms differ with the severity of the upstream stenosis.NEW & NOTEWORTHY Emerging coronary venous retroperfusion treatments, particularly coronary sinus reducer (CSR) for refractory angina linked to myocardial ischemia, show promise; however, their mechanisms of action are not well understood. We find that CSR's effectiveness varies with the severity of coronary stenosis. In moderate stenosis, CSR improves tissue oxygenation by increasing capillary transit time, whereas in severe stenosis, it redistributes blood from nonischemic to ischemic regions and reduces capillary flow heterogeneity.

History of the cutaneous microcirculation from antiquity to modern times.

 This review spans a wide arc from the first observations of the early anatomists to the present day. William Harvey was the first to describe the heart as the centre of the large and small circulatory system. He thus replaced the previously valid system of Galenos, It was Marcello Malpighi who first described that the capillary system connects the arteries with the veins. In 1688 Antoni van Leeuwenhoek (1632-1686) confirmed these results with a paper on capillary perfusion in the caudal fin of the glass eel. It was then Hermann Boerhave (1668-1738, Leiden) who was the first to carry out microcirculation tests on patients. He studied the microcirculation in the human bulbar conjunctiva. Even today, microcirculation studies in the conjunctiva bulbi of patients are carried out today. Until 1831, it was never quite clear whether the observations reported belonged mainly to the field of microcirculation, which had not yet been defined. This was done in Great Britain by Marshall Hall (1790-1857). Technical Improvements allowed increasingly sophisticated studies of the morphological structure of the terminal vasculature. According to Gustav Ricker (1870-1948, Vienna), the terminal vasculature comprises the functional unit of the smallest arteries, arterioles, capillaries and venules. In 1921 it was still thought that the blood circulation was the sole response to the pumping action of the heart. Even the classic work by Bayliss on the myogenic hypothesis (later referred to as "blood flow autoregulation") initially received little attention. More strikingly, even the findings of August Krogh, for which he received the Nobel Prize in Medicine in 1920 (for his discovery of the mechanisms of capillary motor regulation), were ignored. During an outstanding autoregulation symposium held in 1963 a broad consensus was reached on active and passive mechanisms, which is more or less valid till today. The mechanisms of regulation of capillary blood flow are now largely understood, although not completely resolved. The development of video systems with recording capability and automated off-line recording of capillary erythrocyte velocities allowed the application of morphological and dynamic studies of cutaneous capillaries in humans. These reopened the field of physiological or pathophysiological questions again for many groups worldwide. Since 1955, many publications on "microcirculation (5423)" and "capillary microscopy (2195)" have been listed in pubmed.