Microcirculatory Flow Research Articles

Transcriptomics analysis reveals molecular mechanism of softening and cell wall polysaccharides-disassembling in peaches treated by flow microcirculation of sodium nitroprusside medium

Peach (Prunus persica L. Batsch. var. compressa Bean) is prone to softening during storage, and this leads to a marked deterioration in quality and shortened shelf life. The influences of sodium nitroprusside (SNP) atomization on softening development, cell wall ultrastructure, cell wall polysaccharides metabolism in peach fruit stored at 0 ± 0.5 °C for 60 d were explicated. SNP atomization treated fruit, when contrasted to the control, exhibited higher firmness, contents of chelate-soluble pectin (CSP), sodium carbonate-soluble pectin (SSP), cell wall materials (CWM), cellulose and hemicellulose (HC), but lower water-soluble pectin (WSP) content. SNP treatment suppressed activities of cell wall-degrading relevant enzymes, the disassembly of cell wall structure, and the decomposition of middle lamella and plasma membrane in peach fruit. The RNA sequencing results suggested that the differentially expressed genes from amino sugar metabolic process (beta-D-xylosidase, BXL), galactose metabolism (beta-galactosidase, β-Gal), pentose and glucuronate interconversions (polygalacturonase, PG), cellular carbohydrate metabolic process (xyloglucan- endotransglucosylase/hydrolase, XTH), and expansin (Exp) were associated with cell wall degradation in peaches with aerosolized water (control) or SNP treatments. Based on these results, the delayed softening of peaches with SNP atomization was ascribed to cell wall polysaccharides degradation regulated by gene expression levels and enzymes.

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.

Skin microcirculation in middle-aged men with newly diagnosed arterial hypertension according to remote laser Doppler flowmetry data.

This work aims to study the functional state of resistive skin microvessels in patients with newly diagnosed arterial hypertension (AH), using portable laser Doppler flowmetry (LDF) devices. The study included 89 men aged 30 to 60 years (44.4 ± 8.5) who had no known medical complaints, subjectively considered themselves healthy, and did not take medications on a regular basis. All the men underwent LDF on the left forearm, daily blood pressure (BP) monitoring (DBPM) on the left arm, echocardiography, and laboratory tests. According to DBPM data, the men were divided into two groups. The control group (CG) consisted of 30 men with normal BP, and 59 men were included in the AH group. According to LDF data, in men with AH, there is a decrease in the amplitude (tone increase) of neurogenic and myogenic vasomotion, a decrease in the amplitude of pulse oscillations of microcirculatory flow, a decrease in perfusion efficiency of endothelial, neurogenic, myogenic and pulse mechanisms of tissue perfusion regulation. Of all tone-forming mechanisms, only the myogenic mechanism has a weak negative correlation with systolic blood pressure level. The amplitude of pulse oscillations demonstrates the highest degree of correlation with blood pressure parameters. The functional disorders of vasomotor activity of resistive skin microvessels revealed in men with AH have minor correlations with the level of blood pressure. Despite this, the use of portable devices for remote LDF may be a useful method for the dynamic monitoring of patients with hypertension, which requires further research. • In early arterial hypertension (AH) perfusion efficiency in skin is reduced. • Neurogenic and myogenic vasomotor tones increase with the development of AH. • Pulse oscillations demonstrate the highest correlation with blood pressure. • Wrist-mounted LDF monitors are promising for early hypertension monitoring.

Cutaneous Microcirculatory Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion

PURPOSE: Cutaneous devices employing near infrared spectroscopy (NIRS) for continuous free flap tissue oxygenation (StO2) monitoring have several limitations. Confounding factors like skin pigmentation and thickness, ambient light incursion, and inconsistency at the skin-sensor interface can alter StO2 measurements. As an alternative means for peripheral free flap monitoring, we present a novel probe that calculates microvascular blood flow velocity by measuring tissue thermal diffusion. This device is cutaneous, wireless and not subject to the same confounding variables as NIRS. METHOD: The cutaneous perfusion sensor includes 5 thermistors, a Bluetooth chip, and small battery mounted on circuit board. A thermal actuator (4-mm diameter) delivers a small amount of thermal power to the surface of the skin. The device is cutaneously mounted with a silicone acrylate adhesive onto target tissue. The diffusion of heat is measured and analytically converted into a measurement of microcirculatory blood flow velocity. Rapid thermal diffusion occurs in situations of high tissue perfusion, while slower thermal diffusion indicates slower or absent near-surface blood flow. This device was tested alongside Vioptix T.Ox in a porcine rectus abdominus myocutaneous flap model of arterial and venous pedicle occlusion. After flap elevation, the flow device and T.Ox were applied to the skin. Acland clamps were alternately applied to the flap artery and veins to achieve conditions of flap ischemia and congestion, each lasting 15 minutes, with a 15 minute intervening recovery period. In total, 10 devices were tested on 16 flaps in 10 separate pigs over 60 unique vaso-occlusive events. RESULTS: Continuous monitoring was accomplished and no connection loss was observed with either T.Ox or the novel devices. Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded with vascular occlusion and release, and closely followed StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities, ranging from 0.76 to 0.83. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements, with a cross-correlation of 0.87. CONCLUSION: This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Because flow measurements are not affected by the variable lighting and light absorbing properties of tissue, this monitoring strategy has the potential to provide more consistent information than NIRS. Future studies will characterize longevity of the device over a period of several days.

Unfractionated Heparin Protects Microcirculation in Endotoxemic Rats by Antagonizing Histones

IntroductionLevels of extracellular histones are highly increased in sepsis and may facilitate microcirculatory dysfunction. Unfractionated heparin (UFH) binds histones and neutralizes their cytotoxicity. We investigated the effect of UFH on microcirculatory dysfunction by interacting with extracellular histones in endotoxemic rats. MethodsTwenty-four Wistar rats were randomly divided into three groups: control, lipopolysaccharide (LPS) group, and LPS + UFH group. In the LPS and LPS + UFH groups, 10 mg/kg LPS was injected to induce endotoxemia, and 100 IU/kg/h UFH was administered intravenously in the LPS + UFH group. The rats underwent midline laparotomy, and then intestinal microcirculation was evaluated using an incident dark field microscope. Circulating histones and microstructures of the rat intestinal microvascular endothelium were also detected. Additionally, the antagonistic effect of UFH on histone-induced cytotoxicity was investigated in human intestinal microvascular endothelial cells. ResultsUFH protected the microcirculation of the intestinal serosa and mucosa in endotoxemic rats, as evidenced by increased total vessel density, perfused vessel density, and proportion of perfused vessels of both the serosa and mucosa, and increased microcirculatory flow index of the mucosa in the LPS + UFH group. UFH treatment decreased the levels of circulating histones and alleviated intestinal microvascular endothelial injuries in endotoxemic rats. Furthermore, UFH inhibited histone cytotoxicity in vitro. ConclusionsUFH attenuated microcirculatory dysfunction in endotoxemic rats by antagonizing extracellular histones, thereby providing a potential therapeutic strategy for sepsis.

Combination of ethrel and antiseptic medium flow of micro‐circulating improves shelf‐life quality of kiwifruit after long‐term controlled atmosphere storage

AbstractThe uneven maturity and severe internal rot of kiwifruit were rapidly accelerated when transferred to room temperature after long‐term controlled atmosphere storage. In this study, the effects of ethrel combined with different flow microcirculation of antiseptic mediums on the shelf‐life quality of “Qinmei” kiwifruit stored at 20°C were evaluated. Results indicated that the combined aerosolization application of 500 mg/L natamycin, 7.5% w/w H2O2 and 0.5 mg/L atomized ozone could control the decay incidence and respiratory rate of ethrel‐treated kiwifruit. Further studies indicated that ethrel and O3 treatment greatly increased the activities of chitinase, β‐1,3‐glucanase, catalase, and superoxide dismutase and produced higher ascorbic acid levels (151.16 mg·100 g−1/FW) to enhance disease‐resistant of kiwifruit. This treatment could inhibit the activity of polyphenol oxidase and delay the process of membrane lipid peroxidation, contributing to preserving the integrity of cell structures well. Moreover, ethrel + O3 treatment could effectively reduce ethylene production (3.12 μl/kg/h) to delay the ripening and senescence of fruit stored at 20°C. More importantly, this treatment exhibited the lowest contents of decay incidence (9.75%), total bacterial count (4.07 log cfu/g), and yeasts and molds (4.18 log cfu/g), and thus extended the shelf life for up to 16 days. Therefore, a combination of ethrel and ozone is a potentially effective method for the maintenance of the shelf‐life properties of kiwifruit after long‐term cold storage.Novelty impact statementIn this study, the treatment of ethrel‐treated with aerosolized ozone of flow microcirculation of 0.5 mg/L O3 could effectively suppress ripening and senescence, enhance antioxidant capacity and disease resistance, reduce the degree of membrane lipid peroxidation, and considerably preserve the integrity of cell structures, which contributed to preventing the penetration of pathogens, retarding the decay incidence, and delaying the shelf‐life quality deterioration of kiwifruit transferred to room temperature after long‐term controlled atmosphere storage.

Characteristics of sublingual microcirculatory changes during the early postoperative period following cardiopulmonary bypass-assisted cardiac surgery-a prospective cohort study.

Persistent microcirculatory dysfunction associated with increased morbidity and mortality. Interventions in the early resuscitation can be tailored to the changes of microcirculation and patient's need. However, there is usually an uncoupling of macrocirculatory and microcirculatory hemodynamics during resuscitation. Current research on the patterns of microcirculatory changes and recovery after cardiopulmonary bypass (CPB)-assisted cardiac surgery is limited. This study aimed to analyze changes in the microcirculatory parameters after CPB and their correlation with macrocirculation and to explore the characteristics of microcirculatory changes following CPB-assisted cardiac surgery. Between December 2018 and January 2019, 24 adult patients with indwelling pulmonary artery catheters after elective cardiac surgery using CPB were enrolled in this study. Both microcirculatory and macrocirculatory parameters were collected at 0, 6, 16, and 24 hours after admission to the intensive care unit (ICU). Video images of sublingual microcirculation were analyzed to obtain the microcirculatory parameters, including total vascular density (TVD), perfused small vessel density (PSVD), the proportion of perfused small vessels (PPV), microvascular flow index (MFI), and flow heterogeneity index (HI). The characteristics of microcirculatory parameter change following cardiac surgery and the correlation between microcirculatory parameters and macroscopic hemodynamic indicators, oxygen metabolic indicators, and carbon dioxide partial pressure difference (PCO2gap) were analyzed. There were significant differences in the changes of TVD (P=0.012) and PSVD (P=0.005) during the first 24 hours postoperatively in patients who underwent CPB-assisted cardiac surgery. The microcirculatory density parameters (TVD: r=-0.5059, P=0.0456; PVD: r=-0.5499, P=0.0273) were correlated with oxygen delivery index (DO2I) at 24 hours after surgery. The microcirculatory flow parameters (PPV: r=0.4370, P=0.0327; MFI: r=0.6496, P=0.0006; and HI: r=-0.5350, P=0.0071) had a strong correlation with PCO2gap at 0 hour after surgery. TVD and PSVD might be two most sensitive indicators affected by CPB-assisted cardiac surgery. There was no consistency between microcirculation and macrocirculation until 24 hours following cardiac surgery, meaning the improvement of systemic hemodynamic indicators does not guarantee correspondently improvement in microcirculation. Early controlled oxygen supply after CPB-assisted cardiac surgery may be conducive to the resuscitation of patients to a certain extent.

Decreased renal cortical perfusion, independent of changes in renal blood flow and sublingual microcirculatory impairment, is associated with the severity of acute kidney injury in patients with septic shock

BackgroundReduced renal perfusion has been implicated in the development of septic AKI. However, the relative contributions of macro- and microcirculatory blood flow and the extent to which impaired perfusion is an intrinsic renal phenomenon or part of a wider systemic shock state remains unclear.MethodsSingle-centre prospective longitudinal observational study was carried out. Assessments were made at Day 0, 1, 2 and 4 after ICU admission of renal cortical perfusion in 50 patients with septic shock and ten healthy volunteers using contrast-enhanced ultrasound (CEUS). Contemporaneous measurements were made using transthoracic echocardiography of cardiac output. Renal artery blood flow was calculated using velocity time integral and vessel diameter. Assessment of the sublingual microcirculation was made using handheld video microscopy. Patients were classified based on the degree of AKI: severe = KDIGO 3 v non-severe = KDIGO 0–2.ResultsAt study enrolment, patients with severe AKI (37/50) had prolonged CEUS mean transit time (mTT) (10.2 vs. 5.5 s, p < 0.05), and reduced wash-in rate (WiR) (409 vs. 1203 au, p < 0.05) and perfusion index (PI) (485 vs. 1758 au, p < 0.05); differences persisted throughout the entire study. Conversely, there were no differences in either cardiac index, renal blood flow or renal resistive index. Sublingual microcirculatory variables were not significantly different between groups at study enrolment or at any subsequent time point. Although lactate was higher in the severe AKI group at study enrolment, these differences did not persist, and there were no differences in either ScvO2 or ScvCO2-SaCO2 between groups. Patients with severe AKI received higher doses of noradrenaline (0.34 vs. 0.21mcg/kg/min, p < 0.05). Linear regression analysis showed no correlation between mTT and cardiac index (R-0.18) or microcirculatory flow index (R-0.16).ConclusionRenal cortical hypoperfusion is a persistent feature in critically ill septic patients who develop AKI and does not appear to be caused by reductions in macrovascular renal blood flow or cardiac output. Cortical hypoperfusion appears not be associated with changes in the sublingual microcirculation, raising the possibility of a specific renal pathogenesis that may be amenable to therapeutic intervention.Trial Registration Clinical Trials.gov NCT03713307, 19 Oct 2018.

In vivo real-time red blood cell migration and microcirculation flow synergy imaging-surveyed thrombolytic therapy with iron-oxide complexes.

Nanotherapeutics as a nascent method has attracted widely interest on the treatment of thrombosis. However, due to the limited temporal and spatial resolution of conventional imaging modalities, the dynamic visualization the thrombogenesis and evaluation of the effect of thrombolytic drugs are facing severely difficulties in vivo. In addition, the development of high targeting, short circulation time, and small size thrombolysis nanotherapeutics agents requires further research. Herein, we report a synergy imaging modality that combining a label-free capillary microscopy and laser speckle microcirculation imaging, which realized dynamic visualization of single red blood cell migration and large-field dynamic blood flow. In this work, we investigated the red blood cells migration and blood flow velocity response before and after treated through introducing a functional nano-thrombolytics, iron-oxide complexes coated urokinase (IPN@UK) on an orthotopic animal model in vivo. The functionalized IPN@UK nanocomposites exhibited outstanding thrombolysis effect. Significantly, whole-course changes, including red blood cell activity, complex thrombolytic therapeutics, were well surveilled and evaluated using dual-modality combining imaging strategy. These results show this synergy imaging strategy not only can achieve multiscale non-invasive visualization of dynamic thrombus events in real-time, but also can quantify hemodynamics information of thrombus. Our study demonstrates the potential of this synergy imaging method, which for early detection of thrombus, evaluation of the effect of drug thrombolysis, developing the thrombolytic drugs, and imaging-guide thrombolytic therapy in living systems.

Absent Metabolic Transition from the Early to the Late Period in Non-Survivors Post Cardiac Surgery.

After major surgery, longitudinal changes in resting energy expenditure (REE) as well as imbalances in oxygen delivery (DO2) and distribution and processing (VO2) may occur due to dynamic metabolic requirements, an impaired macro- and microcirculatory flow and mitochondrial dysfunction. However, the longitudinal pattern of these parameters in critically ill patients who die during hospitalization remains unknown. Therefore, we analyzed in 566 patients who received a pulmonary artery catheter (PAC) their REE, DO2, VO2 and oxygen extraction ratio (O2ER) continuously in survivors and non-survivors over the first 7 days post cardiac surgery, calculated the percent increase in the measured compared with the calculated REE and investigated the impact of a reduced REE on 30-day, 1-year and 6-year mortality in a uni- and multivariate model. Only in survivors was there a statistically significant transition from a negative to a positive energy balance from day 0 until day 1 (Day 0: −3% (−18, 14) to day 1: 5% (−9, 21); p < 0.001). Furthermore, non-survivors had significantly decreased DO2 during the first 4 days and reduced O2ER from day 2 until day 6. Additionally, a lower REE was significantly associated with a worse survival at 30 days, 1 year and 6 years (p = 0.009, p < 0.0001 and p = 0.012, respectively). Non-survivors seemed to be unable to metabolically adapt from the early (previously called the ‘ebb’) phase to the later ‘flow’ phase. DO2 reduction was more pronounced during the first three days whereas O2ER was markedly lower during the following four days, suggesting a switch from a predominantly limited oxygen supply to prolonged mitochondrial dysfunction. The association between a reduced REE and mortality further emphasizes the importance of REE monitoring.

Microcirculation assessment of dexmedetomidine constant rate infusion during anesthesia of dogs with sepsis from pyometra: a randomized clinical study

ObjectiveTo compare dexmedetomidine and fentanyl constant rate infusions in anesthetic protocols for septic dogs with pyometra, using microcirculatory, hemodynamic and metabolic variables. Study designRandomized clinical study. AnimalsA total of 33 dogs with pyometra with two or more systemic inflammatory response syndrome variables undergoing ovariohysterectomy. MethodsDogs were randomized into two groups: group DG, dexmedetomidine (3 μg kg–1 hour–1; 17 dogs) and group FG, fentanyl (5 μg kg–1 hour–1; 16 dogs) infused during isoflurane anesthesia and mechanical ventilation. Microcirculation flow index (MFI), total vessel density and De Backer score were assessed using orthogonal polarization spectral imaging at the sublingual site. Heart rate, invasive blood pressure, temperature, arterial blood gas analysis and lactate concentration were obtained at various time points. Variables were recorded at baseline (BL), immediately before (T0), 30 (T30) and 60 (T60) minutes after infusion, and 60 minutes after surgery. Data were analyzed using the Shapiro-Wilk test. To compare variables between groups, the unpaired Student t test was used. Comparison between evaluation time points was performed with two-way anova for repeated measures. Where statistical significance was detected, the Bonferroni post hoc test was used. ResultsMFI was significantly higher in group FG at T30. Mean arterial pressure at T30 was higher in group DG (89 ± 15 mmHg) than in group FG (72 ± 13 mmHg). Lactate concentrations were not significantly different between groups at each time point. Both groups had similar clinical outcomes (mortality, extubation time and occurrence of hypotension and bradyarrhythmias). Conclusions and clinical relevanceDexmedetomidine (3 μg kg–1 hour–1) without a loading dose can be included in the maintenance of anesthesia in dogs with pyometra and sepsis without compromising microcirculation and hemodynamic values when compared with fentanyl (5 μg kg–1 hour–1).

Physical Properties of Blood and their Relationship to Clinical Conditions.

It has been long known that blood health heavily influences optimal physiological function. Abnormalities affecting the physical properties of blood have been implicated in the pathogenesis of various disorders, although the exact mechanistic links between hemorheology and clinical disease manifestations remain poorly understood. Often overlooked in current medical practice, perhaps due to the promises offered in the molecular and genetic era, the physical properties of blood which remain a valuable and definitive indicator of circulatory health and disease. Bridging this gap, the current manuscript provides an introduction to hemorheology. It reviews the properties that dictate bulk and microcirculatory flow by systematically dissecting the biomechanics that determine the non-Newtonian behavior of blood. Specifically, the impact of hematocrit, the mechanical properties and tendency of red blood cells to aggregate, and various plasma factors on blood viscosity will be examined. Subsequently, the manner in which the physical properties of blood influence hemodynamics in health and disease is discussed. Special attention is given to disorders such as sickle cell disease, emphasizing the clinical impact of severely abnormal blood rheology. This review expands into concepts that are highly topical; the relation between mechanical stress and intracellular homeostasis is examined through a contemporary cell-signaling lens. Indeed, accumulating evidence demonstrates that nitric oxide is not only transported by erythrocytes, but is locally produced by mechanically-sensitive enzymes, which appears to have intracellular and potentially extracellular effects. Finally, given the importance of shear forces in the developing field of mechanical circulatory support, we review the role of blood rheology in temporary and durable mechanical circulatory support devices, an increasingly utilized method of life support. This review thus provides a comprehensive overview for interested trainees, scientists, and clinicians.

Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery.

Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome. Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week. The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it. Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.

Does the age of packed red blood cells, donor sex or sex mismatch affect the sublingual microcirculation in critically ill intensive care unit patients? A secondary interpretation of a retrospective analysis

In vitro studies have thoroughly documented age-dependent impact of storage lesions in packed red blood cells (pRBC) on erythrocyte oxygen carrying capacity. While studies have examined the effect of pRBC age on patient outcome only few data exist on the microcirculation as their primary site of action. In this secondary analysis we examined the relationship between age of pRBC and changes of microcirculatory flow (MCF) in 54 patients based on data from the Basel Bedside assessment Microcirculation Transfusion Limit study (Ba2MiTraL) on effects of pRBC on sublingual MCF. Mean change from pre- to post-transfusion proportion of perfused vessels (∆PPV) was + 8.8% (IQR − 0.5 to 22.5), 5.5% (IQR 0.1 to 10.1), and + 4.7% (IQR − 2.1 to 6.5) after transfusion of fresh (≤ 14 days old), medium (15 to 34 days old), and old (≥ 35 days old) pRBC, respectively. Values for the microcirculatory flow index (MFI) were + 0.22 (IQR − 0.1 to 0.6), + 0.22 (IQR 0.0 to 0.3), and + 0.06 (IQR − 0.1 to 0.3) for the fresh, medium, and old pRBC age groups, respectively. Lower ∆PPV and transfusion of older blood correlated with a higher Sequential Organ Failure Assessment (SOFA) score of patients upon admission to the intensive care unit (ICU) (p = 0.01). However, regression models showed no overall significant correlation between pRBC age and ∆PPV (p = 0.2). Donor or recipient sex had no influence. We detected no significant effect of pRBC on microcirculation. Patients with a higher SOFA score upon ICU admission might experience a negative effect on the ∆PPV after transfusion of older blood.

Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation

ObjectiveThis study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury. MethodsLandrace pigs were divided into a sham operation group (S group, n = 6), ventricular fibrillation control group (VF-C group, n =8) and 654-1 intervention group (VF-I group, n = 8). Hemodynamics was recorded at baseline, at recovery of spontaneous circulation (ROSC), and 1 h, 2 h, 4 h and 6 h thereafter. Sidestream dark field (SDF) technology was used to evaluate and monitor the microcirculation flow index, total vessel density, perfusion vessel ratio, De-Backer score, and perfusion vessel density in animal viscera at various time points. ResultsAfter administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group. ConclusionAdministration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Polyethylene glycol‐20 ameliorates tissue ischemia and improves renal function following traumatic shock

The “Golden Hour” policy used for US Troops in Iraq and Afghanistan has contributed to the highest survival rates for combat injury in history. Anticipated future combat operations require more options to optimize combat casualty care by extending “the Golden Hour” to “the Golden Day.” Low volume resuscitation with polyethylene glycol‐20K (PEG) has been shown to decrease mortality following hemorrhagic shock, however, the effect of PEG on tissue perfusion and renal function has not been determined. We hypothesized that PEG can ameliorate ischemia and prevent renal injury during prolonged traumatic shock. Anesthetized rats received extremity trauma (soft tissue injury and fracture in one hindlimb) and pressure‐controlled hemorrhage, with mean arterial pressure (MAP) maintained at 55mmHg. MAP, heart rate, renal blood flow (RBF, perivascular ultrasonic transit time flow probe), peripheral skeletal muscle microcirculatory flow and tissue oxygen partial pressure (OxyLite needle probes), blood gases, and electrolytes were monitored throughout the experiment. Glomerular filtration rate (GFR) was recorded using a non‐invasive Fluorescein isothiocyanate‐sinistrin transcutaneous technique. After 45 minutes of shock with MAP at 55mmHg, rats were randomly treated with an intravenous bolus of either 7.5% PEG or saline (1.3 ml/kg, n = 5/group). Measurements were continued from the 45th to the 165th minute without MAP control or any other treatment. Compared with saline, PEG markedly improved MAP recovery (P &lt; 0.001) and survival (P &lt; 0.01) (Figures 1A and 1B). Microcirculatory perfusion and oxygen partial pressure were markedly decreased after hemorrhage and saline treatment elicited no additional effect. However, with PEG, the decreases in capillary flow and tissue oxygen levels were significantly attenuated (P = 0.04 and 0.03, respectively) (Figure 2A). Moreover, blood lactate levels continuously increased in the saline group but returned to levels comparable to baseline within 30 minutes after PEG treatment (P &lt; 0.001) (Figure 2B). In the saline group, RBF markedly decreased concomitantly with a sustained increase in renal vascular resistance (RVR) during the shock period. PEG treatment rapidly restored RBF (P &lt; 0.001) to levels comparable to baseline along with a normalized RVR. GFR was diminished in the saline‐treated rats but was improved in the PEG‐treated group (0.07 ± 0.05 vs. 0.67 ± 0.06 ml/min/100g, respectively; P &lt; 0.001). These results provide strong evidence that PEG rapidly improves macro‐ and microcirculatory hemodynamics ameliorates tissue ischemia, and minimize renal injury and mortality following prolonged traumatic shock.

Soluble VE‐cadherin disrupts endothelial barrier function via VE‐PTP/RhoA signalling

Increased levels of soluble VE‐cadherin fragments (sVE‐cadherin) have previously been linked to inflammation‐induced loss of endothelial barrier function. We hypothesized that sVE‐cadherin independent of pro‐inflammatory stimuli may be critically involved in the context of endothelial barrier dysfunction.Recombinant human sVE‐cadherin (extracellular domains EC1‐5) was generated and verified by sequencing and immunoblotting. Application of sVE‐cadherin on human dermal microvascular endothelial cells (HDMECs) dose‐dependently induced loss of endothelial barrier function as revealed by measurements of transendothelial electrical resistance (TER) and flux of 70 kDa FITC‐dextran across HDMEC monolayers. In an in vivo rat model i.v. application of sVE‐cadherin resulted in loss of endothelial barrier function and reduced microcirculatory flow, which was comparable to the conditions when bacterial Lipopolysaccharide (LPS) was applied in vivo. Immunofluorescence staining and western blot analysis revealed that the functional effects of sVE‐cadherin were paralleled by decreased expression of VE‐cadherin and reduction of α‐/ β‐/ γ‐/ δ‐catenin and tight‐junction associated protein ZO‐1 at the cell borders. VE‐protein tyrosine phosphatase (VE‐PTP) which is associated with VE‐cadherin under resting conditions was removed from the cell borders following application of sVE‐cadherin to HDMEC. These changes were accompanied by intercellular gap formation and increased stress fibers in the actin cytoskeleton. On a mechanistic level, sVE‐cadherin did not induce cell death but increased RhoA activity and reduced extracellular VE‐cadherin interaction as revealed by atomic force measurements. Rho‐kinase inhibitor Y27632 blocked all sVE‐cadherin‐induced effects on endothelial barrier function. Furthermore, VE‐PTP inhibitor AKB9778 attenuated both RhoA activation and all sVE‐cadherin‐induced effects.In summary, sVE‐cadherin disrupts endothelial barrier function by dismantling the VE‐cadherin complex at the cell border via VE‐PTP‐dependent RhoA activation. This points to a novel pathophysiological role of sVE‐cadherin in the context of endothelial barrier dysfunction in inflammation.

Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock

BackgroundFluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.MethodsA model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.ResultsEach treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (p = 0.012) but delayed peripheral perfusion (p = 0.034).ConclusionsCrystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.

Sublingual microcirculatory alterations during the immediate and early postoperative period: A systematic review and meta-analysis.

The incidence of postoperative microcirculatory flow alterations and their effect on outcome have not been studied extensively. This systematic review and meta-analysis were designed to investigate the presence of sublingual microcirculatory flow alterations during the immediate and early postoperative period and their correlation with complications and survival. A systematic search of PubMed, Scopus, Embase, PubMed Central, and Google Scholar was conducted for relevant articles from January 2000 to March 2021. Eligibility criteria were randomized controlled and non-randomized trials. Case reports, case series, review papers, animal studies and non-English literature were excluded. The primary outcome was the assessment of sublingual microcirculatory alterations during the immediate and early postoperative period in adult patients undergoing surgery. Risk of bias was assessed with the Ottawa-Newcastle scale. Standard meta-analysis methods (random-effects models) were used to assess the difference in microcirculation variables. Thirteen studies were included. No statistically significant difference was found between preoperative and postoperative total vessel density (p = 0.084; Standardized Mean Difference (SMD): -0.029; 95%CI: -0.31 to 0.26; I2 = 22.55%). Perfused vessel density significantly decreased postoperatively (p = 0.035; SMD: 0.344; 95%CI: 0.02 to 0.66; I2 = 65.66%), while perfused boundary region significantly increased postoperatively (p = 0.031; SMD: -0.415; 95%CI: -0.79 to -0.03; I2 = 37.21%). Microvascular flow index significantly decreased postoperatively (p = 0.028; SMD: 0.587; 95%CI: 0.06 to 1.11; I2 = 86.09%), while no statistically significant difference was found between preoperative and postoperative proportion of perfused vessels (p = 0.089; SMD: 0.53; 95%CI: -0.08 to 1.14; I2 = 70.71%). The results of the non-cardiac surgery post-hoc analysis were comparable except that no statistically significant difference in perfused vessel density was found (p = 0.69; SMD: 0.07; 95%CI: -0.26 to 0.39; I2 = 0%). The included studies investigate heterogeneous groups of surgical patients. There were no randomized controlled trials. Significant sublingual microcirculatory flow alterations are present during the immediate and early postoperative period. Further research is required to estimate the correlation of sublingual microcirculatory flow impairment with complications and survival.

Abstract No. : ABS3228: Perfusion index - a novel and objective parameter to predict successful lumbar sympathectomy: a case series.

Background and Aims:Lumbar sympathectomy interrupts the sympathetic system of the lower limb, thereby augmenting the flow in microcirculation. This block is assessed by resolution of symptoms, reduced nociception, decreased sweating, and rise of local temperature. Perfusion index(PI) can objectively predict a successful block. complex regional pain syndromeMethods:The trend of perfusion index from the ipsilateral great toe of ten patients undergoing diagnostic lumbar sympathectomy for CRPS (6 patients) and peripheral vascular disease (4 patients), was observed and recorded using Mindray Beneview T8 monitor. The PI at zero and thirty minutes was plotted and the percentage of change was calculated.Results:The trend and behaviour of perfusion index in all patients, irrespective of the chronicity and underlying pathology, was consistent. The rise in PI in the lower limb can be taken as an objective marker of a successful lumbar sympathectomy. Further controlled studies are needed to pin down an absolute percentage rise in PI to predict a successful blockade.Conclusion:PI is a novel and promising parameter which is readily available in operating rooms and can objectively demonstrate a successful lumbarsympathectomy.Perfusion index, lumbosacral plexus, sympathectomy, complex regional pain syndrome