Microcirculatory Flow Research Articles

Reevaluating vitamin C in sepsis and septic shock: a potential benefit in severe cases?

Vitamin C (Ascorbic acid) has evolved as an emergent co-intervention for sepsis and septic shock patients. Multiple studies discussed the pathophysiological value of vitamin C to reserve endothelial functionality and improve microcirculatory flow in these patients. Nevertheless, most randomized clinical trials failed to show the clinical impact of adding vitamin C to sepsis and septic shock. Pneumonia is the most common infection to induce sepsis and septic shock, which could be an acute respiratory distress syndrome. Preliminary in-vitro data support the role of vitamin C in mitigating the risk of acute respiratory distress syndrome (ARDS) development. This review aims to compare and contrast these trials and explore differences in their patients' populations, methodologies, and outcomes, emphasizing pneumonia-induced sepsis and septic shock.

Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: A prospective cohort study.

Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak (TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528-0.818, p = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514-0.800, p = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events.

SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART).

Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission (<24hours). Lactic acidosis, largely due to impairment of the microcirculatory flow due to parasite sequestration, is a main risk factor for poor outcome. There are no adjuvant treatments for severe malaria that target this complication. Sevuparin, a heparin-like drug, binds to Plasmodium falciparum erythrocyte membrane protein blocking merozoite invasion, preventing cytoadherence and transiently de-sequestering infected erythrocytes. Leading to improved microcirculatory flow by reversing/preventing parasite sequestration. If given early during admission this could result in improvements in outcomes. Sevuparin has been shown to be safe and well tolerated in adults with only some mild transient effects on activated partial thromboplastin time (APTT) were reported, without clinical consequences. A Phase I trial designed to provide data on safety, dosing, feasibility of sevuparin as an adjuvant therapy in Kenya and Zambian children with severe malaria complicated by lactic acidosis (> 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient's APTT results using standard methods. The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021).

Transitions from Aerobic to Anaerobic Metabolism and Oxygen Debt during Elective Major and Emergency Non-Cardiac Surgery.

Intraoperative hemodynamic and metabolic optimization of both the high-risk surgical patients and critically ill patients remains challenging. Reductions in oxygen delivery or increases in oxygen consumption can initiate complex cellular processes precipitating oxygen debt (OXD). This study tested the hypothesis that intraoperative changes in sublingual microcirculatory flow reflect clinically relevant transitions from aerobic to anaerobic metabolism (TRANAM). We included patients undergoing elective major and emergency non-cardiac surgery. Macro- and microcirculatory variables, oxygen extraction, and transitions of metabolism were assessed in both cohorts. In the elective group, OXD was progressively increased over time, with an estimated 2.24 unit increase every 30 min (adjusted p < 0.001). Also, OXD was negatively correlated with central venous pressure (ρ = -0.247, adjusted p = 0.006) and positively correlated with stroke volume variation (ρ = 0.185, adjusted p = 0.041). However, it was not significantly correlated with sublingual microcirculation variables. In the emergency surgery group, OXD increased during the first two intraoperative hours and then gradually decreased until the end of surgery. In that cohort, OXD was positively correlated with diastolic arterial pressure (ρ = 0.338, adjpatients and the critically ill patients remains challengingsted p = 0.015). Also, OXD was negatively correlated with cardiac index (ρ = -0.352, adjusted p = 0.003), Consensus Proportion of Perfused Vessels (PPV) (ρ = -0.438, adjusted p < 0.001), and Consensus PPV (small) (ρ = -0.434, adjusted p < 0.001). TRANAM were evident in both the elective major and emergency non-cardiac surgery cohorts independent of underlying alterations in the sublingual microcirculation.

Shenfu injection alleviate gut ischemia/reperfusion injury after severe hemorrhagic shock through improving intestinal microcirculation in rats

BackgroundShenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing. MethodsTwenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP ‘were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed. ResultsSF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group. ConclusionsSF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.

Mimicking blood and lymphatic vasculatures using microfluidic systems.

The role of the circulatory system, containing the blood and lymphatic vasculatures, within the body, has become increasingly focused on by researchers as dysfunction of either of the systems has been linked to serious complications and disease. Currently, in vivo models are unable to provide the sufficient monitoring and level of manipulation needed to characterize the fluidic dynamics of the microcirculation in blood and lymphatic vessels; thus in vitro models have been pursued as an alternative model. Microfluidic devices have the required properties to provide a physiologically relevant circulatory system model for research as well as the experimental tools to conduct more advanced research analyses of microcirculation flow. In this review paper, the physiological behavior of fluid flow and electrical communication within the endothelial cells of the systems are detailed and discussed to highlight their complexities. Cell co-culturing methods and other relevant organ-on-a-chip devices will be evaluated to demonstrate the feasibility and relevance of the in vitro microfluidic model. Microfluidic systems will be determined as a noteworthy model that can display physiologically relevant flow of the cardiovascular and lymphatic systems, which will enable researchers to investigate the systems' prevalence in diseases and identify potential therapeutics.

Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine.

Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.

Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. None. Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index ( r = -0.225; β = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; β = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O 2 /s/10 6 cells; p = 0.002). Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

Assessing the Clinical Outcomes of Voxelotor Treatment in Patients with Sickle Cell Disease

The results of Voxelotor treatment in Sickle Cell Disease, as assessed through clinical outcomes, demonstrated its efficacy in reducing hemolysis and improving hemoglobin levels. This effect can be attributed to Voxelotor's inhibition of HbS polymerization, thereby restoring the deformability and compliance of sickle RBCs. Our mathematical model provided mechanistic insights into how altered rheological properties of sickle RBCs impact their flow dynamics in microcirculation. Specifically, we observed that Voxelotor-induced improvements in RBC deformability and compliance lead to enhanced plasma film height in capillaries, promoting smoother blood flow and reducing the risk of vaso-occlusive events. We established a direct relationship between the molecular mechanism of Voxelotor action and its clinical outcomes. The mathematical model served as a bridge, elucidating how Voxelotor-induced changes in sickle RBC mechanics translate to improved microcirculatory flow and reduced vaso-occlusion. This holistic understanding not only validates the therapeutic efficacy of Voxelotor but also underscores the importance of considering biomechanical factors in evaluating treatment outcomes in SCD. Furthermore, this study highlighted the relevance of microfluidics based diagnostic tools in assessing the efficacy of Voxelotor treatment. By leveraging insights from our mathematical model, microfluidics devices can be designed to mimic physiological conditions and effectively evaluate the deformability of sickle RBCs before and after treatment. This integrated approach not only facilitates the development of personalized therapeutic interventions but also accelerates the translation of novel treatments, such as Voxelotor, from preclinical studies to clinical practice for the management of Sickle Cell Disease. Int. J. Appl. Sci. Biotechnol. Vol 12(1): 46-53.

Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance

Context Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection. Objective To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality. Materials and methods A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1’s safe dosage. Groups for each model were: in vivo—a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro—a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 μM for 30 min). NGR1’s effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated. Results Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 μM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis. Discussion and conclusions Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1’s efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Influence of Gyrotactic Microorganisms on Bioconvection in Electromagnetohydrodynamic Hybrid Nanofluid through a Permeable Sheet

Many biotechnology sectors that depend on fluids and their physical characteristics, including the phenomenon of bioconvection, have generated a great deal of discussion. The term “bioconvection” describes the organized movement of microorganisms, such as bacteria or algae. Microorganisms that participate in bioconvection display directed movement, frequently in the form of upward or downward streaming, which can lead to the production of distinctive patterns. The interaction between the microbes’ swimming behavior and the physical forces acting on them, such as buoyancy and fluid flow, is what drives these patterns. This work considers the laminar-mixed convection incompressible flow at the stagnation point with viscous and gyrotactic microorganisms in an unsteady electrically conducting hybrid nanofluid (Fe3O4-Cu/water). In addition, hybrid nanofluid flow over a horizontal porous stretched sheet, as well as external and induced magnetic field effects, can be used in biological domains, including drug delivery and microcirculatory system flow dynamics. The governing system has been reduced to a set of ordinary differential equations (ODEs) through the use of the group technique. The current research was inspired by an examination of the impacts of multiple parameters, including Prandtl number, Pr, magnetic diffusivity, η0, shape factor, n, microorganism diffusion coefficient, Dn, Brownian motion coefficient, DB, thermophoresis diffusion coefficient, DT, bioconvection Peclet number, Pe, temperature difference, δt, and concentration difference, δc. The results show that as Pr rises, temperature, heat flux, and nanoparticles all decrease. In contrast, when the η0 value increases, the magnetic field and velocity decrease. Heat flow, bacterial density, and temperature decrease as the DB value rises, yet the number of nanoparticles increases. As the DT value increases, the temperature, heat flow, and concentration of nanoparticles all rise while the density of bacteria decreases. Even though temperature, heat flux, nanoparticles, and bacterial density all decrease as δc values climb, bacterial density rises as Dn values do although bacterial density falls with increasing, δt and Pe values; on the other hand, when n values increase, temperature and heat flow increase but the density of bacteria and nanoparticle decrease. The physical importance and behavior of the present parameters were illustrated graphically.

Surmounting photon limits and motion artifacts for biological dynamics imaging via dual-perspective self-supervised learning

Visualizing rapid biological dynamics like neuronal signaling and microvascular flow is crucial yet challenging due to photon noise and motion artifacts. Here we present a deep learning framework for enhancing the spatiotemporal relations of optical microscopy data. Our approach leverages correlations of mirrored perspectives from conjugated scan paths, training a model to suppress noise and motion blur by restoring degraded spatial features. Quantitative validation on vibrational calcium imaging validates significant gains in spatiotemporal correlation (2.2×), signal-to-noise ratio (9–12 dB), structural similarity (6.6×), and motion tolerance compared to raw data. We further apply the framework to diverse in vivo experiments from mouse cerebral hemodynamics to zebrafish cardiac dynamics. This approach enables the clear visualization of the rapid nutrient flow (30 mm/s) in microcirculation and the systolic and diastolic processes of heartbeat (2.7 cycle/s), as well as cellular and vascular structure in deep cortex. Unlike techniques relying on temporal correlations, learning inherent spatial priors avoids motion-induced artifacts. This self-supervised strategy flexibly enhances live microscopy under photon-limited and motion-prone regimes.

Robust Vascular Segmentation for Raw Complex Images of Laser Speckle Contrast Based on Weakly Supervised Learning.

Laser speckle contrast imaging (LSCI) is widely used for in vivo real-time detection and analysis of local blood flow microcirculation due to its non-invasive ability and excellent spatial and temporal resolution. However, vascular segmentation of LSCI images still faces a lot of difficulties due to numerous specific noises caused by the complexity of blood microcirculation's structure and irregular vascular aberrations in diseased regions. In addition, the difficulties of LSCI image data annotation have hindered the application of deep learning methods based on supervised learning in the field of LSCI image vascular segmentation. To tackle these difficulties, we propose a robust weakly supervised learning method, which selects the threshold combinations and processing flows instead of labor-intensive annotation work to construct the ground truth of the dataset, and design a deep neural network, FURNet, based on UNet++ and ResNeXt. The model obtained from training achieves high-quality vascular segmentation and captures multi-scene vascular features on both constructed and unknown datasets with good generalization. Furthermore, we intravital verified the availability of this method on a tumor before and after embolization treatment. This work provides a new approach for realizing LSCI vascular segmentation and also makes a new application-level advance in the field of artificial intelligence-assisted disease diagnosis.

Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data

Objective: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. Methods: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. Results: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. Conclusions: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and β-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Relationship between cardiac output, heart rate and microcirculation in patients with multiorgan dysfunction syndrome

Multiple organ dysfunction syndrome (MODS) is one of the main causes of death in intensive care units. There is evidence that microcirculation in sepsis and coronary shock is regulated separately from hemodynamics. This study investigates the relationship between heart rate (HR), cardiac output (CO) and microcirculation in patients with MODS. This is apartial analysis of the "MODIFY study" (Reducing Elevated Heart Rate in Patients With Multiple Organ Dysfunction Syndrome [MODS] by Ivabradine). During the period 05/2010-09/2011, the microcirculation of 46patients with septic and coronary MODS was measured using the sidestream dark field technique on the day of inclusion and 96 h later. Patients were randomized into acontrol and ivabradine treatment group. Overall, there is arelevant improvement in microcirculation over time small perfused vessels, SPV [%] on day0, d0:56.5 ± 34.2/d4:73.2 ± 22.1 (p = 0.03); perfused vessel density, PVDsmall [1/mm2] d0:7.5 ± 5.0/d4:9.8 ± 3.4 (p = 0.04); proportion of perfused vessels, PPVsmall [%] d0:51.6 ± 31.6/d4:66.7 ± 21.8 (p = 0.04); microcirculatory flow index, MFI d0:1.7 ± 1.0/d4:2.2 ± 0.7 (p = 0.05). Administration of ivabradine shows no effect. In patients with coronary MODS, there is arelevant correlation between microcirculatory parameters and cardiac output (SPV [%]: r = 0.98, p = 0.004). Patients with coronary MODS show better microcirculation values at high heart rates (> 100 bpm), while patients with septic MODS show an opposite relationship. The results indicate that in critically ill patients, depending on the genesis of the MODS, there are different relationships between HF or CO values, on the one hand, and the parameters of the microcirculation, on the other.

Real-time model-based cerebral perfusion calculation for ischemic stroke

Background and ObjectivesClinical diagnosis of ischemic stroke commonly relies on examining cerebral perfusion changes by using computed tomography perfusion (CTP) techniques. However, the radiation dose in CTP is quite higher in comparison to computed tomography angiography (CTA), with associated costs and time. MethodsHence, this study established a lumped-parameter model (LPM) of brain tissue microcirculation (BTM) based on CTA, aiming to achieve real-time calculation of cerebral perfusion. After validation of calculated flow results with clinical data, the BTM-LPM model was used to examine the changes in cerebral perfusion following ischemic stroke, in which the effects of nine anatomical structures of the Circle of Willis (CoW) together with various distribution patterns of stenosis in the feeding arteries were considered. ResultsWhen compared the calculated flow results from BTM-LPM with the clinically measured data of literature, the mean squared error (MSE) value for the feeding arteries was 3.9 % and its total value for microcirculatory flow in each region was 0.1 %. Notably, the calculation time was 35.6 s. In the case of the CoW missing the left and right posterior communicating artery, a 60 % stenosis of the basilar artery is likely to cause ischemic damage to some temporal and occipital lobes of the right and left hemispheres. While in the case of the CoW missing the anterior communicating artery and the left posterior communicating artery, ischemic damage to the entire frontal lobe and parts of the temporal and parietal lobes of the left hemisphere was found when 80 % stenosis occurred in the left internal carotid artery. ConclusionsThe BTM-LPM proposed in this study could accurately calculate cerebral perfusion in real time and demonstrated the importance of CoW anatomy in different ischemic injuries to cerebral tissue. The calculated cerebral perfusion would be a reference value for early diagnosis and preoperative planning of different ischemic injuries to cerebral tissue, thereby the BTM-LPM holds great promising for replacing CTP examination.

Abstract 14679: Microcirculatory Flow and Resistance at Rest and Hyperemia in Relation to Major Adverse Cardiovascular Events in Chronic Coronary Syndrome

Background: The prognostic implications of coronary microvascular dysfunction in an all-comer cohort with chronic coronary syndrome (CCS) are not known. Aim: To investigate the association of baseline resistance index (BRI), index of microcirculatory resistance (IMR), and thermodilution-derived resting- and hyperemic flow velocities (RFV and HFV) with the primary composite endpoint consisting of all-cause mortality, incident myocardial infarction (MI) or hospitalization due to congestive heart failure (CHF) in CCS. Methods: CCS patients undergoing elective coronary angiography (CA) were included. Measurements of corrected IMR, BRI and mean transit time at baseline (Tmn base ) and during hyperemia (Tmn hyp ) were obtained in the LAD. RFV and HFV were calculated as 1/Tmn base and 1/Tmn hyp , respectively. Cox-regression was performed and Kaplan-Meier plots were constructed. Results: We included 503 patients before the coronary anatomy was known and thermodilution measurements in the LAD were obtained in 413 patients. Median age was 68 (IQR 61-74), 127 (25%) were women and 151 (37%) had a flow-limiting epicardial lesion in the LAD. Median follow-up was 5.3 years (IQR 3.0-6.6) and there were 57 events. Log 10 BRI was inversely associated with the primary endpoint before and after fractional flow reserve (FFR) adjustments (HR 0.64 [95% CI 0.42 - 0.97]; Figure 1A). Log 10 IMR was not associated with the primary endpoint (HR 0.94 [95% CI 0.61 - 1.5]; Figure 1B). Log 10 RFV was associated with the primary endpoint before and after FFR- adjustment (HR 1.8 [95% CI 1.2 - 2.7]) whereas log 10 HFV was not (HR 1.2 [95% CI 0.75-1.8]). Conclusion: Low microcirculatory resting resistance and high coronary resting flow velocity in the LAD, indicating impaired autoregulation, were associated with all-cause death, MI and/or CHF in CCS whereas hyperemic microcirculatory resistance and flow were not. Resting flow indices can be used for risk evaluation in patients with CCS undergoing CA. .

Analysis of Microcirculatory Flow Changes After Hemodialysis

Analysis of Microcirculatory Flow Changes After Hemodialysis

SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART)

Background Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission (&lt;24hours). Lactic acidosis, largely due to impairment of the microcirculatory flow due to parasite sequestration, is a main risk factor for poor outcome. There are no adjuvant treatments for severe malaria that target this complication. Sevuparin, a heparin-like drug, binds to Plasmodium falciparum erythrocyte membrane protein blocking merozoite invasion, preventing cytoadherence and transiently de-sequestering infected erythrocytes. Leading to improved microcirculatory flow by reversing/preventing parasite sequestration. If given early during admission this could result in improvements in outcomes . Sevuparin has been shown to be safe and well tolerated in adults with only some mild transient effects on activated partial thromboplastin time (APTT) were reported, without clinical consequences. Methods A Phase I trial designed to provide data on safety, dosing, feasibility of sevuparin as an adjuvant therapy in Kenya and Zambian children with severe malaria complicated by lactic acidosis (&gt; 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient’s APTT results using standard methods. Conclusions The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. Registration PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021)

Dissociation Between Measures of Macrocirculation and Microcirculation in Patients Undergoing Cardiac Surgical Procedure

BackgroundIn the postoperative period of cardiac surgical procedure, there is an imbalance in the ratio of oxygen supply to oxygen consumption that leads to organic dysfunction and death. There is evidence of microcirculation involvement in cardiac surgical procedure, and a dysregulated inflammatory response similar to sepsis can occur. MethodsWe present a cohort of 280 consecutive adults who were monitored in the postoperative period after cardiac surgical procedure. We performed serial measurements of macrocirculatory indices, indices of global oxygenation, CO2-derived indices, and perfusion indices in the first 24 hours postoperatively. ResultsWe identified a dissociation between circulatory macrohemodynamic parameters/global oxygenation indices and the CO2-derived indices. The CO2-derived indices constitute a surrogate for microcirculatory flow and indicate the presence of anaerobic metabolism. ConclusionsA better understanding of these clinical variables will help establish optimal management protocols. It will also aid in the identification of patients in subpopulations with organic dysfunction despite conventional circulatory parameters within normal limits who can be overlooked if this exhaustive hemodynamic evaluation is not performed.