Period Of Occlusion Research Articles

Blood flow modulation to improve motor and neurophysiological outcomes in individuals with stroke: a scoping review.

Ischemic Conditioning (IC) is a procedure involving brief periods of occlusion followed by reperfusion in stationary limbs. Blood Flow Restriction with Exercise (BFR-E) is a technique comprising blood flow restriction during aerobic or resistance exercise. Both IC and BFR-E are Blood Flow Modulation (BFM) strategies that have shown promise across various health domains and are clinically relevant for stroke rehabilitation. Despite their potential benefits, our knowledge on the application and efficacy of either intervention in stroke is limited. This scoping review aims to synthesize the existing literature on the impact of IC and BFR-E on motor and neurophysiological outcomes in individuals post-stroke. Evidence from five studies displayed enhancements in paretic leg strength, gait speed, and paretic leg fatiguability after IC. Additionally, BFR-E led to improvements in clinical performance, gait parameters, and serum lactate levels. While trends toward motor function improvement were observed post-intervention, statistically significant differences were limited. Neurophysiological changes showed inconclusive results. Our review suggests that IC and BFR-E are promising clinical approaches in stroke, however high-quality studies focusing on neurophysiological mechanisms are required to establish the efficacy and underlying mechanisms of both in stroke. Recommendations regarding future directions and clinical utility are provided.

Accelerometer-aided millimeter-wave radar interferometry for uninterrupted bridge displacement estimation considering intermittent radar target occlusion

Monitoring bridge displacement is necessary to detect early signs of damage, prevent catastrophic failures, and maintain public confidence in the safety of critical transportation infrastructure. Radar interferometry is attractive for long-term continuous monitoring of bridge displacements, given its resilience to weather and lighting conditions. However, intermittent radar target occlusions caused by moving vehicles beneath bridges pose challenges during extended continuous monitoring periods. In this study, accelerometer-aided millimeter-wave radar interferometry was explored with an explicit consideration of intermittent radar target occlusion. Radar and accelerometer measurements were first recorded over a short period. Multiple good targets were selected among all radar-detected targets, and their direction-converting factors were estimated using short-period measurements. Subsequently, bridge displacement was continuously estimated by overcoming intermittent radar target occlusions. A displacement reconstruction algorithm was proposed for target occlusion periods, and a multitarget-based phase-unwrapping algorithm was proposed to remove the displacement drift caused by radar target occlusion. The proposed technique was experimentally validated through laboratory tests on a 10-meter-long bridge structure and field tests on two different spans of a footbridge. The technique accurately estimated displacements with overall errors below 0.1 mm, allowing it to be widely applied to bridges with millimeter-scale displacements.

Skin Microvascular Dysfunction in Type 2 Diabetes Mellitus Using Laser Speckle Contrast Analysis and Association with Carotid Intima-Media Thickness.

Background: It is established that diabetes mellitus (DM) is characterized by increased cardiovascular risk associated with subclinical atherosclerosis as well as microvascular alterations. Laser speckle contrast analysis (LASCA) is an innovative, non-invasive method for assessing skin microvascular function. Objectives: We sought to assess skin microvascular function in patients with type 2 DM and matched controls. Methods: Consecutive patients with DM and individuals matched for age, sex and BMI were included in the study. Skin microvascular perfusion was assessed, using LASCA, during baseline, a 5 min occlusion period and a 5 min reperfusion period. Carotid intima-media thickness (cIMT) was measured as a surrogate marker of macrocirculation. Results: In total, 18 patients with DM and 22 in the control group were enrolled. No statistically significant differences were observed in baseline flux, peak flux and percentage decrease during arterial occlusion. During reperfusion, individuals with DM exhibited a smaller peak magnitude compared to controls (147.0 ± 64.7% vs. 189.4 ± 46.0%, respectively; p < 0.05). Moreover, cIMT was higher in patients with DM compared to controls (0.68 ± 0.09 mm vs. 0.60 ± 0.08 mm, respectively, p < 0.01) and was negatively correlated with skin microvascular reactivity in the univariate analysis. In the multivariate analysis, glucose and office systolic blood pressure levels remained significant predictors of microvascular reactivity. Conclusions: Our study shows that patients with type 2 DM exhibit impaired skin microvascular function compared to controls. Furthermore, glucose levels and blood pressure play a key role in microvascular dysfunction. However, additional studies are needed to address the clinical significance of early microvascular changes in DM.

Flow-Mediated Dilatation: Learning Curve Study with a Novice Operator

BackgroundPerforming reproducible flow-mediated dilatation (FMD) measurements can be challenging, especially among inexperienced operators. Our aim was to present the detailed learning curve of a novice operator.MethodsFollowing a one-week basic training period, the operator performed duplicate measurements on 6–8 individuals per week, for six weeks. The operator followed the recommendations of the most recent guideline. Duplex ultrasound was used for the simultaneous and continuous measurement of brachial artery diameter and local blood flow velocity. Following a 1-min recording of baseline diameter (D), FMD was measured after a 5-min period of occlusion of the proximal forearm vessels. Inter-session coefficient of variation (CV) values for D and FMD were calculated for each week.ResultsThe number of volunteers assessed each week were the following: 8, 7, 7, 6, 7, 7 individuals. CV values for both D and FMD exhibited a decreasing trend over the training period, ending at 1.73% for D and 14.24% for FMD at week 6. These CV values are within the range outlined in the most recent FMD guideline for proficiency.ConclusionWithin a reasonable timeframe, and with careful adherence to measurement guidelines, the attainment of sound reproducibility in FMD measurements by a novice operator is feasible.

Poster 191: Does Ischemic Preconditioning of the Operative Limb Reduce Pain after Hip Arthroscopy? A Prospective, Single Blind, Randomized Controlled Trial

Objectives: Improving pain control after hip arthroscopy is an important concern for surgeons and for optimizing the patient experience. Many surgeons use multimodal protocols including peripheral nerve blocks, oral medication, and intra-articular or local anesthetic. Identifying additional preoperative modalities for pain management is a promising way to improve pain and potentially decrease narcotic use. Ischemic preconditioning (IPC) involves the exposure of brief periods of circulatory occlusion and reperfusion which has protective effects on muscular and organ tissues. In addition, studies on the use of IPC prior to knee surgery have shown improvements in postoperative pain and decreased opioid consumption. The purpose of this study was to determine whether preoperative IPC of the operative limb affects postoperative pain scores or opioid consumption after hip arthroscopy. Methods: This is a prospective, single blind, randomized controlled trial. Patients were enrolled between October 2021 and April 2023. Inclusion criteria were patients age ≥ 18 years old undergoing hip arthroscopy by a single surgeon for hip pain in the setting of femoroacetabular impingement or labral tear. Exclusion criteria were history of venous thromboembolism or patients on medications known to increase the risk of blood clots. Following informed consent, patients were randomized to the IPC or control group and were blinded to their treatment group. Limb preconditioning was performed within 24 hours prior to surgery using the Delphi Personalized Tourniquet System (PTS) with the cuff placed on the proximal thigh of the operative limb. Patients in the IPC group received a 30-minute treatment consisting of 3 rounds of 5 minutes at limb occlusion pressure (LOP) alternating with 5 minutes of reperfusion. Patients in the control group received the same protocol at 20% LOP. Hip arthroscopy was then performed according to standard of care. All patients received a standardized preoperative and postoperative pain control regimen. Surveys were administered through RedCap daily from day of surgery through postoperative day 7. Patients were asked to rate their pain 0-10 according to the visual analog scale (VAS) for pain and to record pain medication utilization. Charts were reviewed for baseline characteristics and surgical procedures. Chi-square, independent t tests and paired t tests were used for statistical analysis. Results: A total of 64 patients (31 in the IPC group, 33 in the Control group) were enrolled. Demographics (age, sex, and body mass index) were similar between the IPC and Control groups. There was no significant difference in surgical procedures performed. Survey compliance was higher in the IPC group compared to the control group, 6.1 ± 2.8 days vs. 3.7 ± 3.4 days, respectively (p &lt; 0.05). Both groups reported significant reductions in their VAS for pain scores from day of surgery to postoperative day 6 or 7 (p &lt; 0.05). There was no significant difference between the IPC and control groups in VAS for pain scores at any of the time points from day of surgery to postoperative day 7 (Figure 1). There was also no significant difference between the groups in mean daily opioid consumption (expressed as morphine milligram equivalents) or in acetaminophen consumption at any time point. There were no early complications (within first 7 days postoperatively). Conclusions: Limb IPC does not appear to decrease pain or medication utilization after hip arthroscopy. It is possible that the pain modulating effects of IPC are not as effective when the surgical site is proximal to the site of occlusion. Other factors may have contributed to variability in the reported VAS scores, including differences in fluid extravasation, personal pain tolerances, and utilization of pain control regimen. [Figure: see text]

INVESTIGATING THE RELATIONSHIP BETWEEN BLEEDING, CLOTTING, AND COAGULOPATHY DURING AUTOMATED PARTIAL REBOA STRATEGIES IN A HIGHLY LETHAL PORCINE HEMORRHAGE MODEL.

Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Acute and chronic hyperglycemia blunts microvascular reactivity in postmenopausal women with type 2 diabetes

Type 2 diabetes (T2D) is strongly associated with increased risk of cardiovascular diseases via endothelial dysfunction. Hyperglycemia causes microvascular endothelial dysfunction and reduces muscle perfusion. Near-infrared spectroscopy (NIRS) measures microvascular reactivity in skeletal muscle during vascular occlusion/reperfusion. However, the impact of acute and chronic hyperglycemia on macrovascular endothelial function (brachial flow-mediated dilation, FMD) and microvascular reactivity (NIRS-derived tissue oxygen saturation index, TOI) has not been examined in postmenopausal women with and without T2D. We hypothesized that T2D women would have decreased FMD and TOI responsiveness in the fasted condition and greater vascular impairments during acute hyperglycemia compared to controls.Ten T2D (61 ± 5 years) and 10 normoglycemic postmenopausal women (CON, 62 ± 7 years) participated in the study. Hemoglobin A1C (HbA1C) and blood glucose were measured by finger prick at baseline (fasted condition). Brachial artery FMD was evaluated using ultrasound. Forearm muscle TOI magnitude and slope during arterial occlusion and reperfusion periods were measured using NIRS. An oral glucose tolerance test (OGTT) was performed to induce acute hyperglycemia. Blood glucose, FMD, and TOI were measure at baseline and 1 hour (1-h) after OGTT. Abdominal fat was assessed by waist circumference and visceral adipose tissue (VAT) obtained by a whole-body dual-energy X-ray absorptiometry scan.Fasting HbA1C and glucose, waist circumference, and VAT were higher in T2D compared to CON (all p &lt; 0.05). The increase in blood glucose at 1-h was higher in T2D (Δ143 ± 15 mg/dl) compared to CON (Δ49 ± 5 mg/dl) (p &lt; 0.01). FMD at baseline and the decreases in FMD at 1-h were similar in T2D (Δ-2.2 ± 0.2%) and CON groups (Δ-1.9 ± 0.4%) (all p &lt; 0.01). At baseline, T2D showed blunted TOI occlusion magnitude (T2D: -16 ± 1 vs. CON: -21 ± 2%), TOI occlusion slope (T2D: -0.05 ± 0.01 vs. CON: -0.07 ± 0.01), TOI reperfusion magnitude (T2D: 21 ± 2 vs. CON: 32 ± 3%), and TOI reperfusion slope (T2D: 0.79 ± 0.10 vs. CON: 1.19 ± 0.14) compared to CON (all p &lt; 0.05). At 1-h, T2D exhibited lower TOI occlusion magnitude (T2D: -17 ± 2 vs. CON: -24 ± 3%), TOI occlusion slope (T2D: -0.06 ± 0.01 vs. CON: -0.08 ± 0.01), TOI reperfusion magnitude (T2D: 23 ± 2 vs. CON: 33 ± 4%), and TOI reperfusion slope (T2D: 0.90 ± 0.19 vs. CON: 1.14 ± 0.15) compared to CON (all p &lt; 0.05). HbA1C, a measure of chronic hyperglycemia, was positively correlated with VAT (r = 0.514, p = 0.02) and TOI occlusion slope (r = 0.460, p = 0.04) and negatively correlated with TOI reperfusion magnitude (r = -0.506, p = 0.02) and slope at baseline (r = -0.493, p = 0.03). In conclusion, women with T2D exhibited blunted microvascular reactivity despite similar FMD compared with normoglycemic women in the fasted condition. Acute hyperglycemia further blunted microvascular function, but not macrovascular endothelial function, in women with T2D. Blunted microvascular reactivity was associated with chronic hyperglycemia and elevated VAT in postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia–reperfusion injury

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.

Door to Puncture in Large Vessel Occlusions Pre‐ and Postimplementation of an Automated Image Interpretation and Communication Platform: A Single Center Study

Background Artificial intelligence platforms, like Viz.ai with large vessel occlusion detection, have been used for disease detection and interprovider communication. Whether this software expedites patient transfer and evaluation for treatment needs further exploration. Methods A single‐center retrospective registry was queried for patients with acute large vessel occlusion of the intracranial internal carotid, middle cerebral M1 or M2 segments, or basilar artery treated in a comprehensive stroke network (8 spokes, 1 hub) for 6 months pre‐ and post‐implementation of the Viz large vessel occlusion platform (excluding a 1‐month “washout” period). Robust regression was used to summarize time from initial hospital contact to arterial puncture (primary outcome) between periods, with prespecified subgroup analyses, which were assessed using interaction terms. Results Of the 132 patients (n = 58 preintervention), there were nonsignificantly fewer patients undergoing endovascular therapy in the postintervention period (86.2% preintervention versus 73.0% postintervention; P = 0.07). Among patients who underwent endovascular therapy (n = 50 preintervention, n = 54 postintervention), there was a nonsignificant reduction in time from first contact to arterial puncture (median 155 minute preintervention versus 116 minute postintervention; P = 0.10); however, this became significant in adjusted robust regression accounting for stroke severity, age, Alberta Stroke Program Early Computed Tomography Scale score, daytime versus nighttime and weekend versus weekday arrival, and use of perfusion imaging (β −20.9 [95% CI, −40.5 to −1.4)]. There was also a significant interaction observed for the association between spoke versus hub arrival and the Viz large vessel occlusion period, with shorter intervals observed for transferred patients (n = 32 preintervention with a median of 169 versus 142 minutes for n = 33 postintervention; P interaction &lt;0.01). Conclusion Implementation of the artificial intelligence platform was not associated with shorter intervals between initial hospital contact and neurointervention among all‐comers. A meaningful difference in time to treatment was observed among transferred patients. Larger data sets are needed to validate these observations.

The relationship between trajectories of renal oxygen saturation and acute kidney injury: a prospective cohort study with a secondary analysis

BackgroundAcute kidney injury (AKI) is a major postoperative consequence, affecting prognosis of older patients. Effective prediction or intervention to predict or prevent the incidence of AKI is currently unavailable.AimsDynamic changes of renal tissue oxygen saturation (RSO2) during surgery process are understudied and we intended to explore the distinct trajectories and associations with postoperative AKI.MethodsThis was a secondary analysis including data for older patients who underwent open hepatectomy surgery with informed consent. Latent class mixed models (LCMM) method was conducted to generate trajectories of intraoperative renal tissue RSO2 through different time points. The primary outcome was postoperative 7-day AKI. The univariate and multivariate regression analysis were performed to identify the relationship between distinct trajectories of renal tissue RSO2 and the risk of AKI. Meanwhile, the prediction efficacy of renal tissue RSO2 at different time points was compared to find potential intervention timing.ResultsPostoperative AKI occurred in 14 (15.2%) of 92 patients. There are two distinct renal tissue RSO2 trajectories, with 44.6% generating "high-downwards" trajectory and 55.4% generating "consistently-high" trajectory. Patients with "high-downwards" trajectory had significantly higher risk of postoperative AKI than another group (Unadjusted OR [Odds Ratio] = 3.790, 95% CI [Confidence Interval]: 1.091–13.164, p = 0.036; Adjusted OR = 3.973, 95% CI 1.020–15.478, p = 0.047, respectively). Predictive performance was 71.4% sensitivity and 60.3% specificity for "high-downwards" trajectory of renal tissue RSO2 to identify AKI. Furthermore, the renal tissue RSO2 exhibited the lowest level and the best results in terms of the sensitivity during the hepatic occlusion period, may be considered as a "time of concern".ConclusionsOlder patients undergoing hepatectomy may show high-downwards trajectory of renal tissue RSO2, indicating a higher risk of AKI, and the lowest level was identified during the hepatic occlusion period. These findings may help to provide potential candidates for future early recognition of deterioration of kidney function and guide interventions.

Abstract WP299: Encephalomyosynangiosis Promotes Mature Angiogenesis After Ischemic Stroke

Backgrounds: Current treatments for ischemic stroke patients is ineffective. The brain's inherent ability to self-heal post ischemic stroke is hampered by inadequate blood supply to the affected region. Encephalomyosynangiosis (EMS), a neurosurgical intervention, has proven successful in promoting angiogenesis in patients with Moyamoya disease. We have earlier shown that EMS can increase angiogenesis after stroke in the implanted region, it is not known if those blood vessels are stable or mature. Given that EMS provide balanced growth factors, we therefore hypothesized that EMS enhances stable or mature cerebral angiogenesis in the cortical region surrounding the muscle graft. Methods: Following a 60-minute period of transient middle cerebral artery occlusion (MCAo), mice were assigned randomly to either MCAo alone or MCAo followed by EMS (3-4 hours post MCAo).. Mice were sacrificed at 7, 21, or 70 days post MCAo. A mouse angiogenesis and proteomic profile array was employed to quantify the expression of angiogenic and neuromodulating proteins. Immunohistochemistry was utilized to visualize the bonding of the graft with the brain cortex, changes in vessel density, and pericyte coverage to assess the degree of normal or mature angiogenesis. Results and Conclusions: Preliminary data indicate successful graft implantation and a significantly increased vessel density (P&lt;0.05 compared to the MCAo alone) in proximity to the muscle graft, signifying increased angiogenesis after stroke. EMS-treated mice exhibited an early improvement in sensory motor deficits post-stroke. Analysis of the angiogenesis and proteomic profile array data unveiled a downregulation of antiangiogenic factors (such as interleukin-10 and Fetuin A) and an upregulation of pro-angiogenic cytokines or growth factors (including Fibroblast Growth Factor and C-X-C Motif Chemokine 12) in the EMS group. Co-immunostaining of the endothelial cell marker (Lectin) with the pericyte marker Platelet-Derived Growth Factor Receptor Beta (PDGFRβ) after 70 days of EMS suggested the stability and maturity of new blood vessels. In summary, the EMS procedure appears effective, holding promise for enhanced stable angiogenesis which may help to expedite recovery following ischemic stroke.

Multi-Omics Profiling Identifies Microglial Annexin A2 as a Key Mediator of NF-κB Pro-inflammatory Signaling in Ischemic Reperfusion Injury

Cerebral stroke is one of the leading causes of mortality and disability worldwide. Restoring the cerebral circulation following a period of occlusion and subsequent tissue oxygenation leads to reperfusion injury. Cerebral ischemic reperfusion (I/R) injury triggers immune and inflammatory responses, apoptosis, neuronal damage, and even death. However, the cellular function and molecular mechanisms underlying cerebral I/R-induced neuronal injury are incompletely understood. By integrating proteomic, phosphoproteomic, and transcriptomic profiling in mouse hippocampi after cerebral I/R, we revealed that the differentially expressed genes and proteins mainly fall into several immune inflammatory response-related pathways. We identified that Annexin 2 (Anxa2) was exclusively upregulated in microglial cells in response to cerebral I/R invivo and oxygen-glucose deprivation and reoxygenation (OGD/R) invitro. RNA-seq analysis revealed a critical role of Anxa2 in the expression of inflammation-related genes in microglia via the NF-κB signaling. Mechanistically, microglial Anxa2 is required for nuclear translocation of the p65 subunit of NF-κB and its transcriptional activity upon OGD/R in BV2 microglial cells. Anxa2 knockdown inhibited the OGD/R-induced microglia activation and markedly reduced the expression of pro-inflammatory factors, including TNF-α, IL-1β, and IL-6. Interestingly, conditional medium derived from Anxa2-depleted BV2 cell cultures with OGD/R treatment alleviated neuronal death invitro. Altogether, our findings revealed that microglia Anxa2 plays a critical role in I/R injury by regulating NF-κB inflammatory responses in a non-cell-autonomous manner, which might be a potential target for the neuroprotection against cerebral I/R injury.

Effects of blood flow restriction on mechanical properties of the rectus femoris muscle at rest.

Introduction: This study examined the effects of blood flow restriction (BFR) and reperfusion on the mechanical properties of the rectus femoris muscle at rest (frequency and stiffness). Methods: Fourteen trained men (body weight = 81.0 ± 10.3kg; BMI = 25 ± 3.0m/kg2; height = 181 ± 4cm; training experience = 6.0 ± 2.2years) participated in an experimental session involving their dominant (BFR) and non-dominant leg (control). Muscle mechanical properties were measured using Myoton's accelerometer at the midpoint of the rectus femoris muscle at five time points. In the BFR leg, an 80% arterial occlusion pressure was applied by a cuff for 5min. No cuff was applied in the control leg. Femoral Myoton measurements were taken from both legs 2 and 4min after the start of BRF as well as 30s and 2min after the end of the occlusion period. Results: The two-way ANOVA revealed a statistically significant interaction effect for stiffness and frequency (p < 0.001; η2 > 0.67). The post hoc analysis showed that both stiffness and frequency increased during BFR compared with rest and then dropped to the resting levels post BFR period. Also, stiffness and frequency were higher than control only during the BFR period, and similar during rest and post BFR. Conclusion: These results indicate that the application of BFR at rest leads to significant changes in mechanical properties of the rectus femoris muscle.

Detection of Ischemic ST-Segment Changes Using a Novel Handheld ECG Device in a Porcine Model

BackgroundPortable, smartphone-sized electrocardiography (ECG) has the potential to reduce time to treatment for patients suffering acute cardiac ischemia, thereby lowering the morbidity and mortality. In the UMC Utrecht, a portable, smartphone-sized, multi-lead precordial ECG recording device (miniECG 1.0, UMC Utrecht) was developed. ObjectivesThe purpose of this study was to investigate the ability of the miniECG to capture ischemic ECG changes in a porcine coronary occlusion model. MethodsIn 8 animals, antero-septal myocardial infarction was induced by 75-minute occlusion of the left anterior descending artery, after the first or second diagonal. MiniECG and 12-lead ECG recordings were acquired simultaneously before, during and after coronary artery occlusion and ST-segment deviation was evaluated. ResultsDuring the complete occlusion and reperfusion period, miniECG showed large ST-segment deviation in comparison to 12-lead ECG. MiniECG ST-segment deviation was observed within 1 minute for most animals. The miniECG was positive for ischemia (ie, ST-segment deviation ≥1 mm) for 99.7% (Q1-Q3: 99.6%-99.9%) of the occlusion time, while the 12-lead was only positive for 79.8% (Q1-Q3: 81.1%-98.7%) of the time (P = 0.018). ST-segment deviation reached maxima of 10.5 mm [95% CI: 6.5-14.5 mm] vs 5.0 mm [95% CI: 2.0-8.0 mm] for the miniECG vs 12-lead ECG, respectively. ConclusionsMiniECG ST-segment deviation was observed early and was of large magnitude during 75 minutes of porcine transmural antero-septal infarction. The miniECG was positive for ischemia for the complete occlusion period. These findings demonstrate the potential of the miniECG in the detection of cardiac ischemia. Although clinical research is required, data suggests that the miniECG is a promising tool for the detection of cardiac ischemia.

Вплив об’ємного пневмопресингу низької інтенсивності в осіб з різним типом регуляції автономної нервової системи на центральну гемодинаміку

The purpose of our study was to determine changes in central hemodynamics under the condition of exposure to low-intensity IPC on the lower limbs in individuals with different types of regulation of the autonomic nervous system. The group of 62 participants in age of 18-22 years were investigated. Testing session that included pressure of 40 mmHg and 20-minute period of temporary occlusion of the lower extremities was performed by intermittent pneumatic compression with Recovery Pump PRX device (“Mego Aftek AC Ltd”, Israel). Before, during the exposure and recovery period of the procedure arterial blood pressure was recorded with Korotkov’s auscultative method by mercury tonometer (“Dr.Frei”A-10, Switzerland). For monitoring hemodynamic changes impedance cardiography (ICG) method was applied (“ХАІ-medica”, Kharkiv, Ukraine), by 15 sec. Based on the spectrum power values in the range of 0.15-0.4 (HFnorm), which was calculated according to the formula HFnorm = HF/(HF+LF)∙100%, 3 groups of volunteers were determined by method of sigma deviations. The 1st group included 29 people with a predominance of the sympathetic link of regulation of the autonomic nervous system, HF norm at rest is less than 40 nu. The 2nd - 19 people with a normotonic type of regulation, HFnorm from 40 to 60 nu. The 3rd - 14 people with a predominance of the parasympathetic link, HF norms higher than 60 nu. It has been established that in persons of the 1st group blood pressure maintenance is a result of complex neurohumoral interactions, in the 3rd group - due to vascular components. The decrease in the heart rate and cardiac index in the 1st and 2nd groups is caused by a decrease in venous return to the heart, and in the 3rd group - by contractile function of the heart. The proven impact of non-invasive IPC on peripheral blood circulation improving supports the concept of orthostatic tolerance. Future long-term studies are needed to evaluate the further long-term efficacy of IPC, safety and tolerability of this approach in clinical practice.

Prolonging the zone 1 aortic occlusion time to 4 hours using a partial resuscitative endovascular balloon in a swine model.

The clinical usage of the resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia resulting from complete aortic occlusion. We hypothesized that animals would physiologically tolerate the prolonged partial occlusion using the novel partially occluding REBOA (pREBOA) with survivable downstream injuries. This study used the pREBOA-PRO catheter in a previously established swine model. Female Yorkshire swine (n = 10) underwent a volume-controlled hemorrhage (40% estimated blood). After 1 hour of shock (mean arterial pressure, 28-32 mm Hg), animals were randomized to partial occlusion for either 2 hours or 4 hours. The pREBOA was inflated in zone 1 to achieve partial occlusion defined as a distal systolic blood pressure (SBP) of 20 ± 2 mm Hg. The balloon was deflated at the end of the occlusion period, and animals were resuscitated for 2 hours. Tissues were examined for gross and histologic injury. The primary endpoint was histologic organ injury, and secondary end points were hemodynamic variables and degree of distal organ ischemia. All animals survived to the endpoint. Both groups had similar proximal and distal SBP at baseline, with a divergence of pressures ranging from 55 mm Hg to 90 mm Hg on inflation. The lactate levels increased throughout the occlusion and decreased approximately 40% during the observation period. More animals required norepinephrine and fluid in the 4-hour group compared with the 2-hour group. There was no gross small bowel ischemia noted in the 2-hour animals. The 4-hour group had surgically resectable patchy short segment ischemia. Neither group showed nonsurvivable organ ischemia on pathology or laboratory values. This is the first study showing that the zone 1 aorta can be occluded for over 4 hours using a new pREBOA device without need for balloon titration. In conclusion, simple changes in balloon design offer reliable partial aortic occlusion, with potentially survivable and surgically manageable downstream injuries.

83 Wnt signaling attenuates mechanotransduction and protects against wound occlusion-mediated abolishment of regeneration

OBJECTIVES/GOALS: Current clinical practice recommends occlusive dressings (e.g., film and hydrocolloid) for wounds with variable regenerative capacities. However, clinical evidence suggests that occlusion may hinder regeneration. Our objective was to test the impact of occlusion on regeneration using animal models. METHODS/STUDY POPULATION: The murine wound-induced hair neogenesis (WIHN) is a well-established model of regeneration characterized by de novo hair follicle (HF) formation in the center of large full-thickness wounds. The quantity of neogenic HFs depends on the robustness of Wnt signaling. Optimal tissue mechanics is also required for WIHN. Utilizing the murine WIHN model, we tested the hypothesis that wound occlusion impedes regeneration. We determined how (i) the timing and duration of wound occlusion impacts WIHN, (ii) Wnt signaling influences the occlusion-induced effects on regeneration and (iii) occlusion alters the tissue mechanics of the wound, which establishes the morphogenetic field needed for WIHN. RESULTS/ANTICIPATED RESULTS: Occlusion completely eliminated WIHN. Only a brief period of occlusion between post-wound days 0-3 or 4-7 was sufficient to abrogate WIHN. Microarray and qPCR of open and occluded wounds demonstrated that occlusion promotes fibrosis by upregulating TGF-β2 and mechanotransduction, a mechanosensitive profibrotic pathway. Recruitment of these potent profibrotic pathways generated a symmetrically rigid wound incapable of de novo HF regeneration. Using transgenic animal models with enhanced Wnt signaling, we determined that the ligand-dependent Wnt signaling protected against the occlusion-induced inhibition of WIHN, as well as the occlusion-induced upregulation of both profibrotic pathways. DISCUSSION/SIGNIFICANCE: In animal models, occlusion promoted fibrosis at the expense of regeneration during acute wound healing. Augmented Wnt signaling protected against this effect. Occluding wounds may reduce regeneration. Further studies are warranted to validate these findings.

Hand movements influence the perception of time in a prediction motion task.

Human perception of time is far from accurate and is subject to distortions. Previous research has demonstrated that any manipulation that distorts the perceived velocity of visible moving objects may shift prediction motion (PM) performance during occlusion. However, it is not clear whether motor action has the same influence during occlusion in the PM task. This work evaluated the influence of action on PM performance in two experiments. In both cases, participants performed an interruption paradigm, evaluating if an occluded object had reappeared earlier or later than expected. This task was done simultaneously with a motor action. In Experiment 1, we compared the PM performance according to the timing of the action made while the object was still visible or occluded. In Experiment 2, participants had to perform (or not) a motor action if the target was green (or red). In both experiments, our results showed that the duration of the object's occlusion was underestimated in the specific case of acting during the occlusion period. These results suggest that action and temporal perception share similar neural bases. Future research is needed to confirm this hypothesis.

Ischemic Conditioning to Reduce Fatigue in Isometric Skeletal Muscle Contraction

Ischemic preconditioning (IPC) is a non-invasive protective maneuver that alternates short periods of occlusion and reperfusion of tissue blood flow. Given the heterogeneity in the magnitude and frequency of IPC-induced improvements in physical performance, here we aimed to investigate, in a well-controlled experimental set-up, the local effects of IPC in exposed muscles in terms of tissue oxygenation and muscle fatigue. Nineteen subjects were enrolled in one of the two groups, IPC (3 × 5/5 min right arm ischemia/reperfusion; cuff inflations 250 mmHg) and SHAM (3 × 5/5 min pseudo ischemia/reperfusion; 20 mmHg). The subjects performed a fatiguing contraction protocol before and 30 min after the IPC treatment, consisting of unilateral intermittent isometric elbow flexions (3 s ON/OFF, 80% of maximal voluntary contraction) until exhaustion. While muscle strength did not differ between groups, post- vs. pre-treatment endurance was significantly reduced in the SHAM group (4.1 ± 1.9 vs. 6.4 ± 3.1 repetitions until exhaustion, p < 0.05) but maintained in IPC (7.3 ± 2.0 vs. 7.1 ± 4.3, n.s.). The decrease in tissue oxygenation and the increase in deoxygenated hemoglobin were significantly reduced post- vs. pre-IPC (p < 0.05), but not post- vs. pre-SHAM. The results suggest that IPC delays the onset of fatigue likely through improved metabolic efficiency of muscles.