bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detrimental Effects of Nearby Construction Activity on Endothelial and Vascular Smooth Muscle Function in Cerebral Arteries of Sprague‐Dawley (S‐D) Rats
Authors: Lombard Julian H. , Terashvili Maia , Kozak Kaleigh , Gifford Alison , Uche Nnamdi , Allen Linda Adrienne , Gebremedhin Debebe 
Published: June 2021

The present study assessed the effect of nearby construction activity on endothelium‐dependent vasodilation to acetylcholine (ACh), a crucial diagnostic test, in middle cerebral arteries (MCA) of male Sprague‐Dawley (S‐D) rats. Construction activity began on October 2, 2017 and consisted of installing a utility tunnel for a new heating system near the MCW basic science building, followed by additional construction in front of the adjacent medical education building. The project involved extensive digging and tunneling, and the use of heavy equipment (steam shovels, bulldozers, dump trucks, front end loaders, etc.). Various construction activities continued until the end of May 2018. Most of the construction activity generated high levels of vibration and noise in the patio area just outside the MCW Biomedical Resource Center, which houses numerous rodents and other species used in research projects at the institution. Vibrations were monitored using a system (RPi) designed in our laboratory and consisting of a small computing unit attached to a rolling sensor (low sensitivity) and a Piezo Film Sensor (high sensitivity). The sensor was placed in an empty rat cage and vibrations were quantified as Hz. During the construction period, normal endothelium‐dependent vasodilation in response to ACh was abolished or dramatically reduced in isolated MCA of S‐D rats fed a normal salt diet. MCA from rats studied after completion of construction but housed in the vivarium during construction showed a partial recovery of ACh‐induced dilation, but MCA responses to ACh and vascular NO sensitivity, assessed via vasodilator responses to the NO donor sodium nitroprusside (SNP), in those animals were significantly reduced compared to rats obtained, housed, and studied after completion of the construction project. In separate experiments, activity of Ca2+‐activated maxi K+ channels was lost in isolated cerebral artery smooth muscle cells from S‐D rats housed and studied during the construction period. During the construction period, the RPi system recorded high levels of vibration that corresponded to construction activity outside the building. Following cessation of construction, baseline levels of vibration returned and endothelium‐dependent vasodilation to ACh and vessel NO sensitivity recovered to normal levels. The results of this study show that the noise and vibration associated with nearby construction can have highly deleterious effects upon crucial physiological phenotypes.Support or Funding InformationNIH #R01‐HL128242This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Single‐cell Measurement of Red Blood Cell Oxygen Delivery Rate
Authors: Kim Sangho 
Published: June 2021

Oxygen (O2) is supplied throughout the body by hemoglobin (Hb) bounded in red blood cells (RBCs). The ability of RBCs to deliver O2 has been routinely assessed by P50 using clinical hematology analyzers, defined as the partial pressure of O2 (PO2) required to saturate the Hb in RBCs to 50%. Although this defines the ability of RBCs to carry O2 under equilibrium states, it cannot determine the efficacy of O2 delivery in the dynamic blood flow, which could occur over the span of ~3 s in the microcirculation. Furthermore, while various factors such as pH, temperature and 2,3‐diphosphoglycerate (2,3‐DPG) affecting the O2 dissociation curve (ODC) and P50 have been established, it is unclear how, and the variations of these factors, may influence the RBC O2 delivery on the cellular level. Therefore, in this study, we developed a microwell array oxygen‐sensing chip for measuring the rate of O2 delivery from RBCs at a single‐cell level. Washed RBCs were re‐suspended in an oxygen‐sensitive fluorescence dye solution (ruthenium tris(2,2′‐dipyridyl) dichloride hexahydrate, RTDP) and introduced into the microfluidic device. After trapping of single RBCs in the microwells, heavy mineral oil is used to flush excess RBCs and to isolate single RBCs in the microwell array. Subsequently, the fluorescence intensity of the oxygen‐sensitive dye in the microwell was measured as it gets deoxygenated by N2 gas separated by a PDMS membrane. RTDP fluorescence is quenched in the presence of O2, the fluorescence intensities in the microwells increase as they get deoxygenated by the continuous flow of N2 gas. The rate of O2 release from the single RBC trapped in the microwells, however, would alter the rate of change of microwell PO2. Accordingly, RBCs with higher rates of O2 release would reduce the overall rate of deoxygenation in the microwell, thus reducing the rate of decrease in the PO2. To demonstrate the sensitivity of the device, we deoxygenated the microwells containing RBCs and RBC ghosts (RBCs without Hb). As expected, the PO2 in the microwells containing RBCs was significantly higher (p < 0.0001) than that containing RBC ghosts, due to O2 release from Hb bounded in the RBCs. Additionally, we investigated the potential difference in the O2 delivery rate between density‐fractionated young (top 5% fraction) and old RBCs (bottom 5% fraction). The obtained results showed an apparent difference in the PO2 in microwells with young and old RBCs is statistically significant (p < 0.0001), suggesting that senescent RBCs have a lower O2 delivery rate.Support or Funding InformationNMRC/CBRG/0078/2014 and Biomedical Institute for Global Health Research and TechnologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dopamine Regulates Blood‐Brain Barrier Endothelial Cell Hyperpermeability
Authors: Kosel Kelby , Shaji Chinchusha Anasooya , Zemmedhun Gelilla , Tharakan Binu 
Published: June 2021

Blood‐Brain Barrier (BBB) dysfunction leading to hyperpermeability is one of the major causes of brain edema following conditions such as traumatic and ischemic brain injury. The BBB consists of microvascular endothelial cells that are linked to each other by tight junction and adherens junction proteins and are intracellularly linked to actin cytoskeletal assembly of the cell mainly via zonula occludens‐1 (ZO‐1). Recent studies suggest that the activation of the NLRP3 inflammasome pathway has a major role promoting various pathologies associated with brain injury. An inflammasome is a multiprotein complex that is responsible for the activation of inflammatory responses in the body. Recent studies show that the neurotransmitter, dopamine (DA) is an inhibitor of this pathway. Dopamine regulates bodily functions such as movement, behavior and many systemic functions, but also connects the nervous and immune system in the body. In this study we investigated the effects of DA for its protective effect against oxidative stress‐induced BBB dysfunction and hyperpermeability. In the experiments, hydrogen peroxide (H2O2) was used to induce oxidative stress in rat brain microvascular endothelial cells. Oxidative stress due to increased reactive oxygen species (ROS) formation occurs following trauma and ischemia. Rat brain microvascular endothelial cell monolayers were exposed to H2O2 alone (100μM; 2 hour) or in presence of DA (10μg/ml; 30min) or dopamine D1 receptor agonist (A68930; 10μg/ml; 30min). The changes in tight junction integrity and cytoskeletal assembly were studied using ZO‐1 and β‐catenin immunofluorescence and rhodamine phalloidin staining for F‐actin respectively. Cell viability was studied using Calcein AM cell viability assay. Changes in the formation ROS were studied using 2′, 7′‐dichlorofluorescien diacetate. H2O2 (100μM) treatment resulted in significant increase in monolayer permeability (p<0.05), ROS formation (p<0.05), disruption of the endothelial tight/adherens junctions and induced F‐actin stress fiber formation. Dopamine and A68930 treatment resulted in a decrease in H2O2‐induced monolayer hyperpermeability significantly (p<0.05). Furthermore, DA protected tight junction integrity and actin cytoskeletal assembly. DA and A68930 had no effect on H2O2‐induced ROS formation. The cell viability assay showed that H2O2‐induced barrier disruption is independent of cell death. Our results suggest that one of the major mechanisms for DA‐mediated protection against barrier dysfunction/hyperpermeability may be mediated via inhibiting the NLRP3 inflammasome pathway and not by inhibiting increased ROS formation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fibulin‐4 and Lysyl Oxidase Cooperate to Maintain Arterial Wall Integrity in Large but not Small Vessels
Authors: Halabi Carmen M. , Lin Michelle , Broekelmann Thomas J. , Mecham Robert P. 
Published: June 2021

Fibulin‐4 (FBLN4) is an extracellular matrix protein essential for elastic fiber assembly in large conduit arteries. While its exact role in the process remains unknown, it is hypothesized that, through binding lysyl oxidase (LOX), FBLN4 facilitates elastin crosslinking and mature elastic fiber formation. To assess whether FBLN4 and LOX interact in the process of elastic fiber formation in vivo, we took a genetic approach where we bred recently characterized mice carrying a disease‐causing mutation in Fbln4 (Fbln4E57K) with LOX insufficient (Lox+/−) mice and examined the consequences of LOX insufficiency on the cardiovascular system of Fbln4E57K mice. By 3–4 months of age Fbln4E57K;Lox+/− mice were similar in size to Fbln4E57K mice and littermates. Ascending aortic aneurysms, which were incompletely penetrant and confined to the ascending aorta in Fbln4E57K mice were significantly worsened by LOX insufficiency as they were fully penetrant and extended from the aortic root through the aortic arch in Fbln4E57K;Lox+/− mice. Additionally, arterial tortuosity and elastic fiber fragmentation of large conduit arteries were exacerbated by LOX insufficiency. Interestingly, muscular arteries remained intact. Fbln4E57K;Lox+/− mice had significant cardiac hypertrophy and widening of the pulse pressure that was due to lower diastolic blood compared to Fbln4E57K mice. The cardiac hypertrophy and decrease in diastolic blood pressure are likely a consequence of worsened aortic regurgitation as large artery stiffness was not exacerbated by LOX insufficiency in Fbln4E57K mice. In summary, LOX insufficiency exacerbated the vascular phenotype seen in mice with mutant FBLN4 suggesting that there is a functional interaction between the two molecules. Interestingly, elastic fiber formation was unaffected in muscular arteries raising the possibility that the process of elastic fiber assembly, previously thought to be the same in all elastic tissues, may differ between vascular beds.Support or Funding InformationNIH, NHLBI ‐ 1K08HL135400This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebral Blood Flow Ultrasonography as a Diagnostic Tool for Monitoring Recovery from Concussion in Children and Adolescents
Authors: Favre Michelle E , Breen Paul P , Browne Gary J , Fyffe Andrew , Magalhaes Jennifer , Serrador Jorge M 
Published: June 2021

Approximately 70% of concussions are sports‐related, accounting for up to 1.9 million children and adolescents in the USA every year. Despite the high rates of injury, there are currently no consistent agreements regarding objective measures of diagnosis or severity of injury. Our pilot study determined whether cerebral blood flow (CBF) in the internal carotid artery can be utilized as an objective marker of concussion and recovery trajectory in concussed children and adolescents. We recruited individuals being seen at a concussion clinic with post concussive symptoms (mean= 40 ± 31 days post injury; range= 8–101 days) vs a group of controls who were being seen at the clinic for musculoskeletal injury. Concussed (n=10, 7 male; 12 ± 3 years) and healthy controls (n=8, 5 male; 13 ± 2 years) underwent ultrasound assessments of internal carotid artery blood flow during resting conditions when seated and supine. Continuous blood pressure, ECG, and end‐tidal CO2 were also obtained in participants. Preliminary results showed a trend for an increase in CBF in concussed children when seated (concussed= 644 ± 167 ml/min vs control= 535 ± 118 ml/min; p=0.122) but not when supine (concussed= 628 ± 142 ml/min vs control= 602 ± 140 ml/min; p=696). When comparing the percent of supine CBF when seated, concussed children showed a trend for greater CBF (concussed= 104 ± 19% vs control= 90 ± 11% p=0.101). Interestingly, in our 10 concussed participants, the ratio of seated to supine CBF negatively correlated with the number of days since injury (r= −0.738; p=0.015), suggesting elevated seated CBF may be returning towards normal values. There were no differences in end‐tidal CO2 between concussed and controls when seated (concussed= 40.4 ± 3.0 mmHg vs control= 40.8 ± 3.3 mmHg) or supine (concussed= 40.4 ± 3.8 mmHg vs control= 41.1 ± 3.8 mmHg). However there was significantly increased mean arterial pressure in controls when supine (concussed= 83.4 ± 4.8 mmHg vs control= 92.4 ± 11.9 mmHg; p=0.036) and a trend when seated (concussed= 86.2 ± 5.2 mmHg vs control= 96.0 ± 12.2 mmHg; p=0.074). If additional subjects follow the same pattern, our preliminary data would suggest that concussed children appear to be hyperperfused when seated. While it is unclear why CBF may be elevated when seated, one possibility is that flow is matching the increased metabolic demand associated with neural remodeling after injury. Our preliminary data supports that ultrasonography may be a useful diagnostic tool to monitor recovery from concussion in children and adolescents when taking into account body posture.Support or Funding InformationThe study was supported by the MARCS Institute for Brain, Behaviour and Development, Western Sydney University, Sydney, AUS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neural activity drives dynamic Ca2+ signals in capillary endothelial cells that shape local brain blood flow
Authors: Longden Thomas , Harraz Osama , Hennig Grant , Shui Bo , Lee Frank , Lee Jane , Reining Shaun , Kotlikoff Michael , Kostensis Evi , König Gabriele , Hill‐Eubanks David , Nelson Mark 
Published: June 2021

Brain capillaries constitute a vast, arborescent network of microscopic tubes composed of endothelial cells (ECs) that lie in close apposition to all neurons. Capillaries send long‐range electrical signals to regulate arteriolar diameter and control blood flowing into the brain, but it is unknown whether higher resolution control of blood flow exists within the capillary bed. Here, we demonstrate that capillary ECs exhibit recurrent, long‐lasting, high‐amplitude, local Ca2+ signals in vivo that depend on neuronal activity. These signals are mediated by Gq‐protein‐coupled receptors, prominently including prostaglandin E2‐induced activation of the EP1 receptor, and reflect Ca2+ release through endoplasmic reticulum IP3 receptors and Ca2+ entry through TRPV4 channels. EC Ca2+ elevation at capillary branch points relaxes overlying pericytes, which is associated with a nitric oxide‐dependent increase in local blood flow. Capillary and arteriolar ECs respond robustly to neural stimulation, suggesting coordinated Ca2+ signaling in these compartments directs blood flow to satisfy neuronal metabolic needs.Support or Funding InformationSupported by American Heart Association postdoctoral fellowships and a Scientist Development Grant (14POST20480144; 17SDG33670237 to T.A.L.; 17POST33650030 to O.F.H), the Totman Medical Research Trust (to M.T.N.), Fondation Leducq (to M.T.N.), EC Horizon 2020 (to M.T.N.), and National Institutes of Health (NIH 4P20 GM103644/4‐5 to the Vermont Centre on Behavior and Health (T.A.L); P30‐GM‐103498 to the COBRE imaging facility at the University of Vermont College of Medicine; R24‐HL‐120847 to M.I.K; P01‐HL‐095488, R01‐HL‐121706, R37‐DK‐053832 and R01‐HL‐131181 to M.T.N., and FOR2372 to G.M.K and E.K).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of Non‐Invasive Peripheral Vascular Function to Invasive Measures of Coronary Function in Patients with Suspected Coronary Microvascular Dysfunction
Authors: Nardone Massimo , Miner Steven , McCarthy Mary , Edgell Heather 
Published: June 2021

IntroductionThe purpose of this study is to compare non‐invasive vascular assessments to invasive gold standard measures of coronary flow and resistance in patients with suspected coronary microvascular dysfunction (CMD), a condition driven by systemic endothelial dysfunction. We hypothesize that non‐invasive measures will be associated with both coronary flow and resistance following pharmacological hyperemia.MethodsForty‐one patients with suspected CMD attended the Cardiovascular Integrative Physiology Clinic at Southlake Regional Health Centre. Patients underwent finger‐based arterial tonometry (RHPAT) to non‐invasively quantify microvascular endothelial function (EndoPAT). A subset of participants (n=15) also concurrently completed flow mediated dilation (FMD) of the brachial artery to assess conduit artery endothelial function. Briefly, a standard blood pressure cuff was positioned on the right arm of patients, distal to the elbow joint. Baseline recordings preceded 5 minutes of forearm ischemia, and was followed by cuff deflation, eliciting reperfusion. Within 4 months, patients underwent coronary reactivity testing using the Doppler guidewire method. Specifically, the coronary flow reserve (CFR), and the index of microvascular resistance (IMR) were calculated during pharmacologically‐induced hyperemia using adenosine, then acetylcholine, then dobutamine. Prior to each stimuli, baseline measures were obtained to ensure hemodynamics results to baseline.ResultsRHPAT was negatively correlated to the IMR during dobutamine (r=−0.39, p=0.04), but not the CFR (r=0.14, p=0.49). FMD was negatively correlated to the IMR during adenosine (r=−0.64, p=0.01), but not the CFR (r=0.29, p=0.30). RHPAT and FMD were not correlated to the IMR or CFR during acetylcholine.ConclusionThese preliminary results suggest that measures of non‐invasive peripheral vascular function can predict pharmacologically induced changes in coronary resistance, but not coronary flow.Support or Funding InformationSt. Jude MedicalThe Heart of Gold Cardiac Research FundYork UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ischemia/Reperfusion‐Induced Reduction of Ca2+ Sensitivity in Isolated Cardiomyocytes
Authors: Valencia Sara Osorio , Peirano Felipe , Xi Wang , Han Young Soo , Diaz Rienzi , Sieck Gary 
Published: June 2021

Ischemia/reperfusion (I/R) injury occurs during acute myocardial infarction and is a frequent cause of contractile failure, morbidity and mortality. There is evidence that reduced cardiac contractility following I/R injury is associated with disruption of excitation‐contraction (E‐C) coupling. We hypothesized that I/R injury alters E‐C coupling in cardiomyocytes by reducing the Ca2+ sensitivity of contraction.Cardiomyocytes were isolated from adult rat (Sprague Dawley) hearts using a modified Langendorff system. Cardiomyocytes were then loaded with fura‐2 AM (Ca2+ fluorescent indicator; 1 μM) and electrically stimulated every 2 s (0.5 Hz). Cytosolic Ca2+ concentration ([Ca2+]cyt) and sarcomere length shortening responses to stimulation were simultaneously measured using an IonOptix System equipped with a hypoxia‐regulated incubator system (Live Cell Instrument). To model I/R, cardiomyocytes were initially exposed to normoxia (21% O2) for 30 min followed by 30 min exposure to 2.5% O2 and finally 30 min exposure to normoxia. Throughout the I/R protocol, Ca2+ sensitivity of cardiomyocytes was assessed using a phase loop plot of concurrently measured [Ca2+]cyt and sarcomere length shortening.I/R reduced the extent of sarcomere length shortening, but it had no effect on the amplitude of evoked [Ca2+]cyt transients. Furthermore, I/R reduced Ca2+ sensitivity reflected by a rightward shift in the phase loop plots. These results support the hypothesis that I/R alters E‐C coupling in cardiomyocytes by reducing the Ca2+ sensitivity of contraction.Support or Funding InformationSupported by Mayo FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiac Function and Exercise Capability in Female Goto‐Kakizaki Type‐2 Diabetic Rats after Myocardial Ischemia/Reperfusion
Authors: Omoto Ana Carolina Mieko , do Carmo Jussara M. , da Silva Alexandre A. , Salgado Mateus C. , Salgado Helio C. , Fazan Rubens , Hall John E. 
Published: June 2021

Diabetes mellitus is a major risk factor for coronary artery disease. However, there is conflicting evidence on whether diabetes exacerbates myocardial ischemia/reperfusion (I/R) injury, particularly in females. In this study, we investigated if the deleterious impact of I/R on cardiac function and exercise capability is amplified in female Goto‐Kakizaki (GK, n=6) rats, a model of type‐2 diabetes, 4 weeks after myocardial I/R compared to female Wistar rats (n=5) at 28 weeks of age. Rats were submitted to myocardial I/R by temporary (30 min) ligation of the left anterior descending coronary artery. Long and short axis left ventricle dimensions were obtained before and 4 weeks after I/R procedure using a 21 MHZ transducer (VisualSonics‐VEVO3100®). At the end of week 4, animals were subjected to an aerobic fitness test (maximum velocity test ‐ Vmax) when they were placed on a treadmill, with no inclination, and the speed was increased in steps of 3 m/min every 3 min until animal fatigue. At baseline, female GK rats exhibited higher blood glucose concentration (180±12 vs. 109±4 mg/dL) and lower ejection fraction (63±3 vs. 78±3 %), fractional shortening (18±2 vs. 36±3 %) and cardiac output (75±11 vs. 122±6 mL/min) compared to Wistar controls. At the end of 4 weeks post myocardial I/R, glucose concentration was reduced in GK rats (180 ± 12 to 130 ± 15 mg/dL), associated with a cumulative deficit food intake (~14 g) while no changes were observed in Wistar rats. We also found no alterations in ejection fraction (EF), fractional shortening (FS) or cardiac output (CO) 4 weeks post I/R in female GK (EF: 63±3 to 62±2 %; FS: 18±2 to 21±2 %; CO: 75±11 to 56±4 mL/min), whereas in female Wistar rats there was a significant decrease in EF (78±3 to 66±5 %) and FS (36±3 to 26±4 %) with no change in CO (122±6 to 108±16 mL/min). Despite no evidence of major cardiac dysfunction at rest, a reduced Vmax was observed in GK rats compared to Wistar controls (18±1 vs. 24±2 m/min). These results suggest that despite no major apparent systolic dysfunction after myocardial I/R, female GK rats exhibit reduced exercise capability compared to Wistar rats, highlighting the importance of challenging the heart to unmask potential dysfunctions that may not be apparent at rest.Support or Funding Information(CAPES 88881.187256/2018‐01, NHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.