Microcirculation In Patients Research Articles

Non-linear dynamic processes and their correlation with indicators of microcirculation in patients with obliterating atherosclerosis of the lower extremities arteries according to laser doppler flowmetry

Objective: To study features of nonlinear dynamic and oscillatory processes in the skin microcirculatory flow in patients with obliterating atherosclerosis in lower extremities arteries (OALEA).Material and methods. 56 male patients with obliterating atherosclerosis in the arteries of lower extremities and 15 practically healthy individuals were taken into the study. Microcirculation in the skin on feet with the assessment of nonlinear dynamic processes and spectral wavelet analysis of blood fl ow fl uctuations was studied by laser Doppler flowmetry, device “LACK-M” (firm Lazma, Russia). Normalized amplitude parameters of blood flow fluctuations in frequency ranges of hemocirculation tonus-forming factors were analyzed: endothelial, neurogenic, myogenic. Myogenic microvascular tone and capillary blood flow indices were calculated. To study nonlinear dynamic processes, the following parameters were assessed: fractal dimension, entropy and phase portrait analysis.Results. Spastic-atonic microcirculation disorders were revealed in patients with OALEA. They were characterized with metarteriole constriction and with restriction of capillary blood flow, with an increased myogenic tone and dilated arterioles. Statistically significant shifts in parameters of nonlinear dynamics in this case- in particular, decrease in entropy (–10.6 %) and in dimensions of phase portrait (–9.3%) under energy deficit in oscillatory microcirculation processes (–20.8 %) – can be interpreted as a decrease in complexity of laser Doppler flowmetric signal and better ordering in regulatory mechanisms of the peripheral blood flow.Conclusion. In patients with obliterating atherosclerosis in the arteries of lower extremities, the obtained results indicate significant functional microcirculation disorders of the spastic-atonic nature leading to the restriction of nutritive blood flow and accompanied by the lack of energy in oscillatory processes. These results have also shown the decrease in the system chaos severity which indicates limitation of connections of microcirculation control factors, simplification of the mechanisms of functioning of the microvascular bed and, as a consequence, decrease in the compensatory adaptive potential.

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell's score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: -4.5; -0.92)). The model included variables of age, gender and Bell's score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

Eye Sign is an Alternative for Evaluation of the Microcirculation in Patients with Systemic Sclerosis.

To investigate consistency between eye sign and nailfold video capillaroscopy (NVC) in systemic sclerosis (SSc) patients and to evaluate eye sign with various parameters of disease and potential pulmonary involvement. A total of 60 SSc patients and 20 healthy individuals were enrolled. 20 SSc patients were complicated with pulmonary arterial hypertension (PAH); 20 SSc patients with interstitial lung diseases (ILD); 20 SSc patients without pulmonary involvement. All subjects were assessed using the methods of NVC and eye sign. Skin involvement was evaluated by modified Rodnan skin score (mRSS) and disease activity according to Medsger's severity score (MSS). Clinical manifestations and the presence of autoantibodies were carefully recorded. Any correlations between were evaluated with the Spearman correlation coefficient test. According to the morphological changes revealed by NVC, 3 types of NVC patterns have been characterized (early pattern, active pattern, and late pattern). Eye sign showed distinguishing morphologic changes in three patterns of NVC and pulmonary involvements (PAH vs ILD) in SSc. A positive linear correlation was found between scores of eye sign and NVC in all patients with SSc (r = 0.629, P=0.001). A positive correlation of eye sign was found in all SSc patients with mRSS (r = 0.748, P=0.045) and MSS (r = 0.636, P=0.001). The study demonstrates that eye sign had a high consistency with NVC for the evaluation of the microcirculation in SSc patients and exhibited specific patterns in the early, active, and late phases of SSc. Eye sign can be used as a reliable method to classify and monitor SSc patients and replace the measurement of NVC.

Possibilities of drug correction of the state of the main arteries and microcirculation in patients with chronic heart failure and chronic obstructive pulmonary disease

Introduction. Patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are increasingly found in the clinical practice. The comorbidity of CHF and COPD promotes high mortality in such patients. Therapy that is prescribed to patients with CHF and COPD may not always have a positive effect on the condition of blood vessels. In this regard, researchers began to pay attention to drugs that have a beneficial effect on blood vessels, without worsening the course of CHF and COPD, one of which is meldonium.The purpose of the study. To study the effect of meldonium as part of complex therapy on arterial stiffness and microcirculation in patients with CHF and COPD.Materials and methods. The open randomized study included 60 patients with CHF IIA stage, II–III functional class (clinical recommendations of RKO, OSSN 2020) and COPD of the I–III degree of airflow restriction (classification GОLD 2021) without exacerbation. The patients were divided into 2 groups: the 1st group – the main group (n = 30) with CHF and COPD, which was prescribed meldonium as part of complex therapy at a dosage of 1000 mg/day, the 2nd group – the control group (n = 30) was on therapy only with basic drugs of CHF and COPD. The observation period is 12 weeks.Results. As a result of 12 weeks of therapy with the inclusion of meldonium in the complex therapy of patients with CHF and COPD, a decrease in the stiffness of the main arteries, an improvement in the regulation and parameters of microcirculation, an increase in the frequency of occurrence of the normocirculatory type of microcirculation were noted.Conclusions. A significant useful effect of complex therapy with the inclusion of meldonium on the condition of arterial stiffness and microcirculation in patients with CHF and COPD has been established, which makes it possible to recommend the use of meldonium in this category of patients.

Radionuclide methods in assessing pulmonary perfusion and ventilation in patients with connective tissue dysplasia

Aim. To perform a scintigraphic assessment of the bronchopulmonary system and pulmonary microcirculation in patients with connective tissue dysplasia.Materials and methods. The study included 31 male patients of conscription age with connective tissue dysplasia (CTD), diagnosed according to the 2019 clinical guidelines (average age (19.6 ± 2.6 years)), and 25 practically healthy individuals comparable in gender and age, who formed a control group. All patients underwent planar pulmonary ventilation – perfusion scintigraphy with determination of pulmonary alveolar – capillary permeability.Results. In patients with CTD, the apical to basal perfusion gradient (U/LQ) was on average 24% lower than in the control group (p = 0.046), and alveolar – capillary permeability was higher in both lungs, both at minute 10 and at minute 30.Conclusion. Static pulmonary ventilation – perfusion scintigraphy allows to identify functional disorders in patients with CTD at the preclinical stage: a decrease in the perfusion gradient on average by 24% compared with the control group and an increase in alveolar – capillary membrane permeability.

Thermodilution-derived coronary absolute flow and resistance in patients with different INOCA endotypes

Abstract Background Thermodilution-derived measurement of absolute coronary flow and resistance has been recently validated by using a dedicated microcatheter and a pressure-temperature guidewire. Coronary absolute flow (AbsF) and derived absolute resistance (AbsR) can give precious information about the microcirculation in patients with ischemia and non-obstructive coronary artery disease (INOCA). The correlation with different INOCA endotypes has been so far poorly investigated. Methods 108 INOCA patients underwent a complete evaluation of underwent coronary function testing, including acetylcholine (ACH) provocation testing, adenosine testing (CFR/IMR) and functional assessment of the left anterior descending artery using thermodilution-derived measurement of AbsF and AbsR. Results Among 108 INOCA patients, 64% showed coronary microvascular dysfunction (CMD) with positive ACH reaction (ACH+) and/or abnormal CFR/IMR (CFR/IMR+), of whom 38% presenting with an isolated structural component (CFR/IMR+) and 62% with an isolated vasospastic component (ACH+). Among ACH+ patients, epicardial vasospastic angina was detected in 28.2% of the patients. AbsF was found significantly lower in ACH+ patients than in ACH− patients (0.174±0.09 vs 0.2019±0.09, p=0.03). Similarly, a trend of higher AbsR values was found in ACH+ patients as compared to ACH− (612.5±226.5 vs 524.5±171.2, p=0.07, Fig. 1A). AbsF was found significantly lower in patients with coronary microvascular dysfunction (CMD) than in patients without either vasospastic or structural component of CMD (0.172±0.06 vs 0.202±0.09, p=0.05) and AbsR showed a trend towards higher values in patients with CMD than patients without CMD. (609.3±208.8 vs 557.7±193.1, p=0.08, Fig. 1B) AbsF and AbsR did not differ in patients with and without abnormal adenosine testing only: AbsF (0.176±0.06 vs 0.197±0.09, p=0.31) and AbsR 589.8±183.0 vs 565.2±190.2, p=0.27). A modest correlation was found between AbsQ and IMR (r: −0.2: p: 0.05, Fig. 2). Conclusion Coronary vasomotor dysfunction is highly prevalent in INOCA patients and a complete coronary function evaluation, including provocative test should be performed. Continuous thermodilution is safe and easily implemented in INOCA patients and provide new insights in the assessment of INOCA endotypes with high reproducibility. The exact diagnostic and prognostic value of these measurements, and their optimal cutoff, should be assessed in future studies. Funding Acknowledgement Type of funding sources: None.

Intracoronary thrombolysis facilitated primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients: an updated meta-analysis of randomized controlled trials

Abstract Background Primary percutaneous coronary intervention (PPCI) is the standard reperfusion treatment in ST-segment elevation myocardial infarction (STEMI). However, PPCI is often complicated by microvascular obstruction. Intracoronary thrombolysis (ICT) may mitigate thrombotic burden. Methods We conducted, according to the PRISMA statement, the largest meta-analysis of ICT as adjuvant therapy to PPCI. All relevant studies were identified by searching the PubMed, Scopus, Cochrane Library, and Web of Science, with no time or language restriction. The odds ratio (OR) and mean difference (MD) with a 95% confidence interval (CI) were calculated. Studies included STEMI patients undergoing PPCI receiving ICT. Both safety and efficacy outcomes were analyzed. Data were combined using a random-effects model. Results Thirteen randomized controlled trials (RCTs) involving a total of 1876 (1014 ICT) patients were included. Compared with the control group, ICT in STEMI patients could reduce the incidence of major adverse cardiac events (MACE) (OR 0.65, 95% CI, 0.48–0.86, P=0.003) and improve 6 months left ventricular ejection fraction (MD 3.78, 95% CI, 1.53–6.02, P=0.0010). Indices of enhanced myocardial microcirculation were more common with ICT [Post PCI corrected thrombolysis in myocardial infarction (TIMI) frame count (MD −3.57; 95% CI, −5.00 to −2.14, P<0.00001); myocardial blush grade (MBG) 2/3 (OR 1.76; 95% CI, 1.16–2.69, P=0.008), and complete ST-segment resolution (OR 1.97; 95% CI, 1.33–2.91, P=0.0007). The incidence rate of major bleeding was comparable between the 2 groups (OR 1.27; 95% CI, 0.61–2.63, P=0.53). Conclusions Intracoronary thrombolysis was associated with improved MACE and myocardial microcirculation in patients with STEMI undergoing PPCI, without any significant increase in major bleeding. Our meta-analysis suggests that a targeted ICT is safe and potentially effective to improve PPCI. Nonetheless, the above results necessitate verification in a contemporary large RCT. Funding Acknowledgement Type of funding sources: None.

Sono-assisted-thrombolysis by three-dimensional diagnostic ultrasound improves epicardial recanalization and microvascular perfusion in acute myocardial infarction.

BackgroundThis study aimed to evaluate the multiple interactions between therapeutic ultrasound (TUS), microbubbles (MB), and recombinant tissue plasminogen activator (r-tPA) by using three-dimensional (3D) ultrasound to examine the impact of thrombolysis with r-tPA on epicardial recanalization and microcirculation in patients with acute ST-segment-elevation myocardial infarction (STEMI).MethodsAcute thrombotic occlusion of the left anterior descending (LAD) artery was induced in 32 Bama pigs, who were fed a high-cholesterol diet and randomized into four groups: (I) a 3D-sono-assisted-thrombolysis (3D/TUS + MB + r-tPA) group; (II) a 3D/TUS + MB group; (III) a full-dose r-tPA group; and (IV) a 3D/TUS alone group. Epicardial angiographic recanalization rate, microcirculation in the at-risk myocardium, ST-segment elevation on electrocardiogram, and changes in the at-risk myocardium and the myocardial infarct area were compared between the groups.ResultsAfter treatment, distal LAD recanalization was observed in 87.5% (7/8) of pigs in the 3D/TUS + MB + r-tPA group, which was significantly higher than the rates observed in the 3D/TUS + MB (37.5%) and the full-dose r-tPA (50.0%) groups (all P<0.05). The average acoustic intensity in the 3D/TUS + MB + r-tPA group (193.78±10.15 dB) was also significantly higher than that in the 3D/TUS + MB (154.29±31.94 dB) and the r-tPA (141.42±28.31 dB) groups (all P<0.05). The decrease in ST-segment elevation in the 3D/TUS + MB + r-tPA group (1.31±1.22 mm) was significantly higher than that in the 3D/TUS + MB (5.38±1.77 mm) and the r-tPA (4.30±2.08 mm) groups (all P<0.05). Furthermore, the ratio of the infarcted myocardial area divided by the at-risk myocardial area was markedly lower in the 3D/TUS + MB + r-tPA group (0.51±0.14) than in the 3D/TUS + MB (0.69±0.28) and r-tPA (0.75±0.23) groups (all P<0.05).ConclusionsThree-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ameliorates the thrombolytic effect of r-tPA in acute STEMI.

The state of capillary microcirculation in patients with diabetes mellitus

Objective — to study endothelial alterations at the level of the microcirculatory section of the blood circulation system in patients with diabetes mellitus by using capillaroscopy in the comprehensive examination.&#x0D; Materials and methods. The clinical examination was performed with the involvement of 37 patients with type 1 and type 2 diabetes mellitus, aged 21 to 65 years, with various manifestations and severity of the disease. The patients have been assigned into two groups. The first group (control) consisted of 12 patients without diabetes, the second group (study group) included 37 patients with type 1 and type 2 diabetes mellitus. The state of the microcirculatory bed of the lower extremities was estimated using capillaroscopy by the Dino‑Lite MEDL4N5 Pro capillaroscope (Netherlands).&#x0D; Results. The analysis of indicators of skin microcirculation showed that both quantitative and qualitative changes in skin microcirculation were observed in patients with diabetes mellitus compared to the control group. The color of the background changed from pale pink to deep red, and with a severe form it even had a grayish tint. Various changes in the size and shape of capillaries and capillary loops have been registered, indicating the processes of capillary destruction and neoangiogenesis. The structural changes of the capillaries were especially prominent with clinically pronounced symptoms. The most frequent changes detected were the spiral‑twisted capillaries. The pattern of the venous network was more pronounced; the spastic altered and shortened arterial genua were conjoined with dilated and tortuous venous ones; aneurysmal dilatations and arterio‑venous anastomoses were common. In addition, the capillaroscopic examination makes it possible to observe a decrease in the number of capillaries, which is expressed in varying degrees, up to the formation of so‑called avascular areas. Blood flow is granular, intermittent, its velocity is slowed down.&#x0D; Conclusions. The severity of diabetic microangiopathy is directly proportional to the duration of the disease. The use of indicators of skin microcirculation makes it possible to predict the probability of the development of diabetic microangiopathy and the degree of its expressiveness in different periods of the disease.&#x0D;

Left ventricular function and coronary microcirculation in patients with mild reduced ejection fraction after STEMI

BackgroundThe characteristics of heart failure (HF) with mildly reduced ejection fraction (EF) (HFmrEF) overlap with those of HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) and need to be further explored. This study aimed to evaluate left ventricular (LV) function and coronary microcirculation in patients with mildly reduced ejection fraction after acute ST-segment elevation myocardial infarction (STEMI).MethodsWe enrolled 119 patients with STEMI who had undergone speckle tracking imaging and myocardial contrast echocardiography during hospitalization from June 2016 to June 2021. They were classified into normal, HFmrEF, and HFrEF groups according to their left ventricular EF (LVEF): ≥ 50%, 40–50%, and ≤ 40%, respectively. The data of the HFmrEF group were analyzed and compared with those of the normal and HFrEF groups.ResultsHFmrEF was observed in 32 patients (26.9%), HFrEF in 17 (14.3%), and normal LVEF in 70 patients (58.8%). The mean global longitudinal strain (GLS) of all patients was − 11.9 ± 3.8%. The GLS of HFmrEF patients was not significantly different from that of the HFrEF group (− 9.9 ± 2.5% and − 8.0 ± 2.3%, respectively, P = 0.052), but they were both lower than that of the normal group (− 13.8% ± 3.5%, P < 0.001). The HFmrEF group exhibited significantly poorer myocardial perfusion index (1.24 ± 0.33) than the normal group (1.08 ± 0.14, P = 0.005) but displayed no significant difference from the HFrEF group (1.18 ± 0.19, P = 0.486). Moreover, a significant difference in the incidence of regional wall motion (WM) abnormalities in the three groups was observed (P = 0.009), and the WM score index of patients with HFmrEF was 1.76 ± 0.30, similar to that of patients with HFrEF (1.81 ± 0.43, P = 0.618), but poorer than that in the normal group (1.33 ± 0.25, P < 0.001).ConclusionsGLS is a more sensitive tool than LVEF for detecting LV systolic dysfunction. The LV systolic function, coronary microcirculation, and WM in patients with HFmrEF was poorer than that of patients with normal LVEF, but comparable to that in patients with HFrEF. Patients with HFmrEF after STEMI require more attention and appropriate management.

Clinical Effect of Emergency Dermabrasion Combined with Biological Dressing A on Wound Microcirculation and Preventing Sepsis in Deep Degree-II Burns.

Objective The aim of this study is to explore the clinical effect of emergency dermabrasion combined with biological dressing A on wound microcirculation and preventing sepsis in deep degree-II burns. Methods A total of 90 patients with deep degree-II burns admitted to the hospital were retrospectively enrolled between January 2020 and January 2022. According to different treatment methods, they were divided into the control group (42 cases, biological dressing A) and the observation group (48 cases, emergency dermabrasion combined with biological dressing A). The clinical curative effect in both groups was observed. The wound repair rate and wound healing quality, and changes in levels of wound microcirculation-related indexes (serum epidermal growth factor (EGF), wound blood flow, and partial pressure of transcutaneous oxygen) and inflammatory cytokines (C-reactive protein (CPR), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT)) before treatment, at 3d and 7d after treatment were compared between the two groups. The incidence of wound infection and sepsis in both groups was recorded. Results The wound healing time in the observation group was significantly shorter than that in the control group, and wound healing quality in the observation group was better than that in the control group (P < 0.05). At 3 d and 7d after treatment, the levels of serum EGF, wound blood flow and partial pressure of transcutaneous oxygen in both groups were all increased (P < 0.05), which were higher in the observation group than those in the control group (P < 0.05). The levels of CRP, IL-6, ESR, and PCT in both groups were all decreased (P < 0.05), which were lower in the observation group than those in the control group (P < 0.05). There was no significant difference in incidence of sepsis between observation group and control group (4.17% (2/48) vs. 7.14% (3/42)) (Fisher = 0.539). Conclusion Emergency dermabrasion combined with biological dressing A can effectively improve wound microcirculation in patients with deep degree-II burns, promote wound healing, shorten wound healing time, improve wound healing quality, effectively control inflammatory response, and prevent sepsis.

Evaluation of Macular and Peripapillary Blood Flow in Response to Intraocular Pressure Reduction in Patients With Posner-Schlossman Syndrome.

Purpose: The study aimed to evaluate the effect of intraocular pressure (IOP) reduction on macular and peripapillary microcirculation in patients with Posner–Schlossman syndrome (PSS) by optical coherence tomography angiography (OCTA). Methods: A prospective comparative study was conducted. Patients diagnosed with PSS at the Eye Center of Xiangya Hospital, Central South University, from February 2020 to November 2021 were consecutively included. OCTA was used for the macular and peripapillary microcirculation measurements, and optical coherence tomography (OCT) was employed for the retinal nerve fiber layer (RNFL) and lamina cribrosa depth (LCD) measurements. The patients received OCT and OCTA examinations at baseline and 1 week post-treatment when the IOP was under control. Changes in macular and peripapillary microcirculation, RNFL, and LCD were calculated for all the analyzed areas. Results: Twenty-one eyes from 21 patients were included in the study. Pre-treatment and post-treatment IOP were 43.17 ± 10.36 mm Hg (range, 30–60 mm Hg) and 17.17 ± 2.85 mm Hg (range, 13–23 mm Hg), respectively. No statistically significant changes were detected in RNFL, LCD, or macular and peripapillary microcirculation after significant IOP reduction. Conclusion: The results suggested that a large IOP reduction may not result in a significant increase in peripapillary and macular capillary perfusion in patients with PSS.

Improved Retinal Microcirculation in Mild Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms Who Received the Medical Food, Ocufolin®.

PurposeTo evaluate the effects of Ocufolin® on retinal microcirculation in patients with mild diabetic retinopathy carrying MTHFR polymorphisms.MethodsIn a prospective, case-controlled study, eight patients with mild diabetic retinopathy and MTHFR polymorphisms and 15 normal controls (NC) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal blood flow velocity (BFV) was measured using Retinal Function Imager. Retinal tissue perfusion (RTP, blood flow rate per inner retinal volume) was calculated within a 2.5 mm diameter circle centered on the fovea. The eight retinopathy patients received Ocufolin® for 6 months, and their imaging was performed at baseline, 4 months, and 6 months. The NC group was imaged once.ResultsBCVA and vascular indices of DR + PM patients at baseline were below those of NC and improved after Ocufolin® administration. Compared to baseline, DR + PM patients had significantly improved BCVA during the follow-up period (P < 0.05). RTP and arteriolar BFV were significantly increased at 6 months (P < 0.05), approaching NC.ConclusionOcufolin® may be effective in improving both visual acuity and retinal microcirculation in patients with DR + PM. Further studies with increasing sample size, and longer duration, including cases with severe DR, are needed.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. RAS demonstrated a loss of medium-sized vessels (0.2-0.3 mm)comparedwithdonorkidneys (P=0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

The role of coronary flow reserve (CFR) and fractional flow reserve (FFR) in acute coronary syndrome - systematic review

The methods used to appreciate the degree of coronary stenosis such as CFR and FFR, come to complement the coronary angiography and help the interventional physician during PCI. Furthermore, CFR and FFR measured immediately after reperfusion, in patients with ACS, may act as a prognosis factor for myocardial infarction.Changes in coronary microcirculation in patients with ACS and NSTEMI correlate to the degree and extent of tissue lysis processes.So far, there are few data revealing the degree of microvascular bed injury and vasodilator capacity in patients with acute myocardial infarction. In this article, we will refer to some studies in the field.

Binary classification models for identification of the most significant features of hemorheology and microcirculation in patients with transport oxygen disturbances

Binary classification models for identification of the most significant features of hemorheology and microcirculation in patients with transport oxygen disturbances

Evaluation of Microcirculation in Optic Nerve Head Using Laser Speckle Flowgraphy in Active Thyroid Eye Disease.

Background Laser speckle flowgraphy (LSFG) can be used to estimate optic nerve blood flow. This study used LSFG to evaluate optic nerve microcirculation in patients with thyroid eye disease (TED). Methods This was a retrospective review of patients with active TED who underwent LSFG between October 2020 and June 2021. The mean blur rate (MBR) for different severities of active TED was analyzed by one-way analysis of variance (ANOVA). Results A total of 30 patients (60 eyes) with a diagnosis of active TED who underwent LSFG were included. The mean age was 49 (range, 33–74) years. Mean best-corrected visual acuity was the worst in the group with sight-threatening active TED (0.29 ± 0.33 logarithm of the minimum angle of resolution, p = 0.01). The MBR-overall was the highest in the group with mild active TED (28.5 ± 2.7), followed by that in the moderate to severe (23.6 ± 3.2), and in the sight-threatening (20.2 ± 4.3) active TED groups (p < 0.001). The MBR-vessel was 57.1, 47.0, and 39.3 in the mild, moderate to severe, and sight-threatening active TED groups, respectively (p < 0.001). The MBR-tissue was 16.9, 14.4, and 12.0 in the mild, moderate to severe, and sight-threatening active TED groups, respectively (p < 0.001). Conclusions This study demonstrates that optic nerve blood flow is lower with more severe active TED. In addition, LSFG is an effective, objective, and noninvasive method for evaluating the severity of TED.

Relationship Between Muscle Cramps and Diabetic Retinopathy in Patients with Type 2 Diabetes.

AimPatients with type 2 diabetes (T2DM) often suffer from muscle cramps of varying severity. Studies have shown that muscle cramp is closely related to local microcirculation perfusion disorders. Diabetic retinopathy can not only reflect the microcirculation perfusion in the eye but also the systemic microcirculation in patients with diabetes. The aims of this study were to investigate the relationship between muscle cramps and diabetic retinopathy in patients with type 2 diabetes.MethodsA total of 150 adult patients with type 2 diabetes were enrolled and administered a questionnaire on muscle cramping, along with a visual analogue scale for pain. Diabetic retinopathy (DR) was determined by using fundus photography and graded as non-proliferative DR (NPDR) and proliferative DR (PDR). To assess whether there was an association between the muscle cramps and diabetic retinopathy, we conducted binomial logistic regression analysis.ResultsOur study revealed that 48% of patients with T2DM experienced muscle cramps in the past three months. Patients self-reported suffering from muscle cramps exhibited a higher prevalence of DR (61% vs 38%, P < 0.05) and PDR (22% vs 4%, P < 0.05) compared with patients without muscle cramps. Serum 25-(OH) vitamin D, calcium, and magnesium levels were not significantly different between patients with and without muscle cramps. After adjusting for age, duration of diabetes, HbA1c, vitamin D, potassium, calcium, and magnesium, we demonstrated that diabetic retinopathy (OR, 2.18; 95% CI, 1.01–4.69; P< 0.05) and albumin (OR, 0.90; 95% CI, 0.82–1.00; P< 0.05) were highly associated with muscle cramps. Binomial logistic regression analysis also indicated that severity of DR is associated with muscle cramps. In addition, DR and PDR were found to be associated with muscle cramp frequency (P for trend < 0.05), duration (P for trend < 0.05), and pain severity (P for trend < 0.05).ConclusionMuscle cramps occur frequently in diabetes and are correlated with diabetic retinopathy and albumin. Patients with PDR exhibited a higher frequency, severity, and longer duration relative to those with NPDR or without DR. Our findings suggested that muscle cramps in individuals with T2DM might be a result of microvascular dysfunction. Modulation of microvascular perfusion might thus provide a therapeutic target for alleviating muscle cramps.

Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction.

IntroductionClopidogrel has been demonstrated to be effective in improving coronary microcirculation (CM) among patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytics. Ticagrelor is a more potent adenosine diphosphate (ADP) receptor blocker proven to be superior to clopidogrel among patients with acute coronary syndromes. The present study aimed to compare the effects of ticagrelor and clopidogrel on CM in patients with STEMI treated with fibrinolytics.MethodsThe present study prospectively included 48 patients participating in the TREAT trial, which randomly assigned patients with STEMI undergoing fibrinolysis to ticagrelor versus clopidogrel. The primary endpoint of this study was the evaluation of the CM using the global myocardial perfusion score index (global MPSI) obtained by myocardial contrast echocardiography (MCE). Platelet aggregation to ADP was evaluated by Multiplate® and expressed as area under the curve (AUC).ResultsThe global MPSI demonstrated no differences between the groups [mean 1.4 (1.2–1.5) in the ticagrelor group and 1.2 (1.2–1.5) in the clopidogrel group (p = 0.41)]. Platelet aggregability was lower in the ticagrelor group (18.1 ± 9.7 AUC), compared to the clopidogrel group (26.1 ± 12.5 AUC, p = 0.01).ConclusionWe found no improvement in coronary microcirculation with ticagrelor compared to clopidogrel among patients with STEMI treated with fibrinolytics, despite the fact that platelet aggregation to ADP was lower with ticagrelor.Clinical Trials RegistrationNCT03104062.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02061-0.

Impaired Microvascular Function in Patients With Critical COVID-19.

OBJECTIVES:Severe coronavirus disease 2019 is characterized by infected microvascular endothelial cells. The primary aim of this study was to investigate microvascular function in patients with critical coronavirus disease 2019.DESIGN:A prospective observational study was conducted in which patients with critical and severe COVID-19 were investigated during acute disease phase and at least 3 months after disease onset.SETTING:Single-center study at Danderyd University Hospital.PATIENTS:Twenty-three patients with critical coronavirus disease 2019 treated with noninvasive or invasive mechanical ventilation, seven patients with severe COVID-19 with dyspnea or need of oxygen supply up to 8 L/min, and 15 noncoronavirus disease controls.INTERVENTIONS:None.MEASUREMENTS:Skin perfusion was investigated through laser speckle contrast imaging before and after iontophoresis of acetylcholine and sodium nitroprusside for determination of the endothelial-dependent and the endothelial-independent vasodilation, respectively.MAIN RESULTS:Patients with critical COVID-19 had higher basal skin perfusion during both the acute (34 ± 9 perfusion unit; p = 0.0003) and the postinfectious phase (29 ± 8 perfusion unit; p = 0.04), compared with noncoronavirus disease controls (23 ± 7 perfusion unit). In addition, endothelial-dependent and endothelial-independent vasodilation were reduced in patients with critical COVID-19 during the acute disease phase (p < 0.001 for both), whereas no significant differences between patients and controls were found during the postinfectious phase. In patients with severe COVID-19, basal skin perfusion and endothelial-dependent vasodilatation were not significantly changed, whereas endothelial-independent vasodilatation was reduced (p = 0.02) compared with controls.CONCLUSIONS:Changes in skin microcirculation in patients with critical COVID-19 indicate that the infection induces a systemic microvascular impairment with persisting long-term effects on the microvascular function.