bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐traumatic stress disorder does not affect cerebrovascular reactivity (1068.18)
Authors: Stojanovic‐Radic Jelena , Reyes Levy , Ghobreal Bemin , Blatt Melissa , Acosta Amanda , Chandler Helena , Serrador Jorge 
Published: June 2021

Post‐traumatic stress disorder (PTSD) is a chronic psychiatric disorder, with symptoms of hyperarousal, which can alter the biological stress response. Our objective was to determine whether possible increased sympathetic tone in veterans with PTSD affected cerebrovascular function due to altered autonomic control. To assess this we measured sympathetic activity from low frequency blood pressure (BP) and heart rate (HR) variability and cerebrovascular function during hyper/hypocapnia using transcranial Doppler in 29 Veterans (10 with PTSD). There was no difference in BP or cerebral flow velocity in the middle (MCA: 51±5 vs 53±3 cm/s) or anterior cerebral artery (ACA: 48±7 vs 49±3 cm/s). Examination of autonomic indicators found no difference in low frequency power in HR or BP variance. Similarly PTSD status did not affect cerebrovascular reactivity for either the MCA (2.2±0.1 vs 2.2±0.1 %/mmHg) or ACA (2.0±0.2 vs 2.3±0.2 %/mmHg). Surprisingly, regardless of PTSD status, all veterans had a blunted response to hypercapnia (MCA: 1.3±0.2; ACA: 1.3±0.2 %/mmHg) compared to hypocapnia (MCA: 2.8±0.2; ACA: 2.7±0.2 %/mmHg). In contrast to our hypothesis, we did not find increased sympathetic activity in PTSD or impaired cerebral blood flow regulation. One explanation for this finding is that our PTSD sample was not of the hyperarousal type. Since we anticipate that hyperarousal is associated with increased sympathetic outflow, if our subjects mainly had dissociative type PTSD, there could be no difference in autonomic function. The finding of impaired vasodilation to CO2 but not vasoconstriction in all Veterans may indicate impaired cerebral vascular function.Grant Funding Source: Supported by NIH R21DC009900 (Serrador) as well as the WRIISC and the Office of VA Public Health
Sudden onset of hearing loss after cerebral ischemia (1068.3)
Authors: Kamat Pardip , Kalani Anuradha , Tyagi Suresh , Tyagi Neetu 
Published: June 2021

Although clinical reports suggest hearing loss in stroke patients but the mechanism is still unclear. Synapse, connexin and sodium epithelial channel proteins involved in processing of sound from auditory cortex to cochlea. Therefore, we hypothesize that hearing loss after cerebral ischemia is associated with alteration in synapse, gap junctions and sodium epithelial channel (ENaC) proteins. To test this hypothesis, we employed male wild type mice; 1) Sham, 2) WT+ ischemia reperfusion (I/R). Ischemia was performed for 60 min and reperfusion for 24 h. The infarct area was measured using 2,3,5‐triphenyltetrazolium chloride staining. Permeability was determined by Evans blue extravasation. In order to accomplish the proposed objectives, we performed physiological, behavior, molecular and immunohistochemistry approaches. The hearing thresholds were determined by recording the auditory brainstem response. We found that brain edema, infarct size and Evans blue leakage were increased in I/R as compared to sham‐operated group. Caspase‐3,‐9 and TUNEL positive cells were increased in ischemic cortex as compared to non‐ischemic cortex, indicates apoptosis and neuronal damage. Moreover, increased expressions of MMPs (MMP‐2,‐9,‐13), IL‐6 and decreased expressions of tight junction proteins in I/R group as compared to control group, signifies inflammation and blood brain barrier (BBB) disruption. We also observed decrease levels of PSD95, SAP97, Cx‐43, ENaCβ, ENaCγ and increase expression of Cx‐45, whereas no change was observed in Cx‐26 in I/R as compared to sham‐operated group. Reduced auditory response confirmed by sound pressure level (SPL) indicates hearing loss. These data suggest that hearing loss in I/R mice was primarily due to alteration in connexin, synapse and ENaC channels.Grant Funding Source: HL107640
Regional cerebral blood flow responses to rapid reductions in blood pressure after high level spinal cord injury: the effect of alpha1‐agonist (1068.8)
Authors: Phillips Aaron , Krassioukov Andrei , Ainslie Philip , Warburton Darren 
Published: June 2021

Spinal cord injury (SCI) above the T6 level frequently results in orthostatic intolerance, but how cerebral blood flow (CBF) responds to an orthostatic challenge in SCI is poorly understood. It is also unclear how alpha1 agonists, meant to improve orthostatic tolerance, influence the CBF response. This study examined: 1) the acute regional CBF velocity (CBFv) response to acute blood pressure (BP) reductions secondary to orthostatic stress in SCI, compared to able‐bodied controls (AB), and 2) the effect of Midodrine (alpha1‐agonist) on orthostatic tolerance and CBFv regulation in SCI. Ten individuals with SCI >T6, and 10 age‐and sex‐matched controls had beat‐by‐beat BP, as well as middle and posterior cerebral artery blood velocity (MCAv, PCAv) recorded during a progressive tilt‐test to quantify the acute CBF response and orthostatic tolerance. Dynamic CBFv‐BP relationships were evaluated from the first 60s after tilt. The SCI group was tested again after administration of an alpha1‐agonist (10 mg midodrine) in order to elevate BP. The acute (i.e., 0‐30s after tilt) MCAv and PCAv responses were similar in SCI and AB. In contrast, Midodrine led to improved PCAv responses 30‐60 s (10±3 vs. 4±2 %decline; p<0.05) after tilt, and a 59% improvement in orthostatic tolerance (p<0.01). The vertebrobasilar region may be particularly susceptible to hypoperfusion in SCI, leading to increased orthostatic intolerance.Grant Funding Source: Supported by HSFC, NSERC, MSFHR & CNF
Reduced cerebral autoregulation as the genesis of symptoms in orthostatic intolerance in elderly (1069.3)
Authors: Sanders Marit , Meel ‐ van den Abeelen Aisha , Slump Cornelis , Lagro Joep , Claassen Jurgen 
Published: June 2021

Background: The prevalence of orthostatic hypotension (OH) increases with age and affects over 50% of elderly visiting a falls and syncope outpatient clinic. OH may be symptomatic or asymptomatic. Surprisingly little is known why serious symptoms as dizziness, falling and syncope occur. A possible cause of symptom development may be cerebral hypoperfusion due to loss of cerebral autoregulation (CA). The purpose of this study is to compare CA in elderly with symptomatic and asymptomatic OH and a control group without OH.Methods: Dynamic CA is assessed in 20 elderly with symptomatic OH, 20 with asymptomatic OH and 20 age‐matched healthy subjects without OH using transfer function analysis (TFA) on blood pressure (BP) and cerebral blood flow velocity (CBFV). Single supine to standing measurements is used to assess time domain changes in BP, CBFV and heart rate. Patient inclusion continues until March 2014.Results: TFA provides outputs gain and phase of the relation between BP and CBFV to assess CA. Time domain analyses will be used to report time to peak and nadir, and time and amount of recovery.Conclusions : This study characterizes CA in symptomatic and asymptomatic OH. The yet preliminary conclusion is that a reduced CA performance is related to the subject group with symptomatic OH in comparison to the asymptomatic OH group.
Nebivolol reduces intracellular Ca2+ and elicits dilations in isolated rat basilar arteries (1070.7)
Authors: Cseplo Peter , Vamos Zoltan , Batai Istvan , Torok Orsolya , Springo Zsolt , Toth Attila , Koller Akos 
Published: June 2021

Experimental and clinical studies have revealed that the antiarrhythmic and antihypertensive, highly selective β1‐adrenerg receptor blocker, nebivolol elicits dilations in peripheral arteries, in which a role for nitric oxide (NO) has been implicated. However, its effect on the diameter of cerebral vessels has not been investigated. We hypothesized that nebivolol increases the diameter of isolated cerebral arteries.Basilar arteries (BA) were isolated from male Wistar rats and were mounted into isotonic myograph chamber. Diameters of vessels were measured by video‐microscopy in response to vasoactive agents, and the intravascular Ca2+ changes was detected by the fura‐2 ratiometric method.Nebivolol elicited significant vasodilation, despite the presence of L‐NAME (NOS inhibitor) or ODQ (guanylate cyclase blocker) or SQ22536 (adenylyl cyclase blocker). Nebivolol significantly reduced the ratiometric calcium‐signal that correlated with changes in diameter.In isolated BA nebivolol: 1) elicits significant dilation, 2) to which NO‐cGMP/cAMP pathway does not contribute significantly, 3) decreases vascular wall [Ca2+]i. (Supported by: OTKA K108444, SROP‐4.2.2.A‐11/1/KONV‐2012‐0024, SROP‐4.2.2.A‐11/1/KONV‐2012‐0017, TAMOP 4.2.4.A/2‐11‐1‐2012‐0001 “National Excellence Program”)Grant Funding Source: OTKA K108444, TAMOP 4.2.4.A/2‐11‐1‐2012‐0001 „National Excellence Program”
Time course of coronary vasodilator response to intravenous adenosine in humans (1071.2)
Authors: Gao Zhaohui , Monahan Kevin , Brandt Kristen , Blaha Cheryl , Herr Michael , Sinoway Lawrence 
Published: June 2021

Measurement of coronary flow velocity reserve (CFVR) has proven useful in assessing coronary vasodilator potential in humans. CFVR is frequently assessed by measuring coronary vasodilator responses to intravenous infusion of adenosine. Importantly, the time course of the coronary vasodilator response to intravenous adenosine infusion has not been well documented. We retrospectively studied this time course during 39 adenosine stress tests obtained in 21 adults (6 F; age range 22‐76 yrs.). Peak coronary blood velocity (CBV) in the left anterior descending artery was assessed non‐invasively in the distal left anterior descending artery using transthoracic Doppler echocardiography before (baseline) and continuously throughout a 6‐min adenosine infusion (0.14 mg/kg/min) in all subjects. CFVR was quantified as CBV peak adenosine/CBVbaseline. Overall, adenosine infusion increased CBV in all subjects (P<0.001) and peak CFVR was observed during the 4th minute in the group as a whole. However, marked variability in the timing of this response was observed. On an individual basis peak CFVR occurred during the 2nd (n=11), 3rd, (n=9), 4th (n=9,) 5th (n=7) and 6th min (n=3) of adenosine infusion. These data suggest that maximal coronary vasodilator responsiveness (i.e., CFVR) occurs variably between the 2nd and 6th minute of adenosine infusion. Based on these findings, we believe the current 6 min adenosine infusion protocol is appropriate. However, we suggest that CBV be monitored during each minute of the infusion so as to capture the true peak response in all subjects.Grant Funding Source: Supported by P01 HL096570 and UL1 TR000127
Coronary perivascular adipose tissue and K+ channel‐mediated vasodilation in lean and obese hearts (1071.4)
Authors: Noblet Jillian , Owen Meredith , Goodwill Adam , Dick Gregory , Tune Johnathan 
Published: June 2021

This investigation examined the mechanisms by which perivascular adipose tissue (PVAT) influences coronary vasodilation. Coronary arteries from lean and obese Ossabaw swine were isolated, incubated with or without 0.3 g of PVAT for 30 min and pre‐constricted with U46619 (1 μM). In arteries cleaned of PVAT, vasodilation to adenosine (0.01‐30 μM) was decreased ~25% in obese arteries. However, the presence of PVAT attenuated adenosine relaxation ~30% in both lean and obese arteries. Pre‐constriction with KCl (60 mM) abolished coronary dilation to adenosine, suggesting activation of K+ channels. Inhibition of KCa channels with penitrem A (1 μM) impaired responses to adenosine in lean (p<0.001), but not obese (p=0.53), arteries. Dilation to the KCa channel agonist NS‐1619 (30 μM) was attenuated by PVAT in lean, but not obese, arteries. Inhibition of KV7 channels with linopirdine (10 μM) impaired adenosine dilation ~56% in lean arteries. Relaxation to the KV7 channel agonist L364,373 (10 μM) averaged 91 ± 5% in lean arteries vs. 55 ± 8% in obese arteries. Incubation with PVAT diminished vasodilation to L364,373 by ~22% in lean arteries, but had no effect in obese arteries. These findings indicate that while PVAT attenuates adenosine‐mediated vasodilation to a similar extent in lean and obese hearts, the contribution of KCa and KV7 channels to coronary vasodilator responses is markedly impaired in the setting of obesity.Grant Funding Source: Supported by HL117620 and HL092245
Sodium butyrate remodels whole genome nucleosome maps and attenuates high fat diet‐induced mitochondrial dysfunction in skeletal muscle from C57BL6/J mice (1072.1)
Authors: Henagan Tara , Navard Alexandra , Ye Jianping 
Published: June 2021

High fat diets (HFDs) largely contribute to the onset and progression of obesity and type 2 diabetes and are used to generate models of diet‐induced obesity and insulin resistance; yet, the epigenetic mechanisms underlying the effects of HFDs are not fully understood. Here, we determined whole genome differences in nucleosome occupancy or positioning in skeletal muscle from C57BL6/J mice fed either a 10% low fat diet (LFD), 60% HFD or 60% HFD plus sodium butyrate (NaB) for 9wks using microccocal nuclease digestion followed by high throughput sequencing (MNase‐seq). Additionally, metabolomics of 45 various acylcarnitine species and ratios and immunohistochemistry for fiber typing were performed in the quadriceps muscle. We show that NaB supplementation prevents HFD‐induced obesity and insulin resistance and that diet‐induced changes in nucleosome occupancy and positioning are associated with parallel increases in muscle mitochondrial function and type 1 oxidative fiber content. Targeted analysis of peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (Pgc1α), also suggests that ‐1 nucleosome positioning within the Pgc1α promoter may be important in diet‐induced mitochondrial adaptation. These data provide additional identified genomic loci that may be epigenetically regulated by diet to determine skeletal muscle mitochondrial adaptation.Grant Funding Source: Supported by NIH NIDDK 5T32‐DK064584‐09 (TMH), NIH COBRE 8P20‐GM103528‐07 and NORC 5P30‐DK072476‐07
Endothelial peNOS signaling and ET‐1 mRNA expression during acute hyperinsulinemia in type 2 diabetes (1072.5)
Authors: Boyle Leryn , Padilla Jaume , Credeur Daniel , Fadel Paul , Thyfault John 
Published: June 2021

Increased endothelin‐1 (ET‐1) and reduced endothelial nitric oxide production are thought to play a role in vascular dysfunction in type 2 diabetes (T2D). However, little is known in humans about changes in endothelial signaling in response to insulin stimulation. Therefore, endothelial nitric oxide synthase (eNOS) signaling and ET‐1 expression were measured from vastus lateralis skeletal muscle biopsies taken before and 60 min into a hyperinsulinemic euglycemic clamp in 6 healthy controls (body fat: 22.8±3.6 %, glucose disposal rate (GDR): 12.6±2.4 mg/kg lean body mass (LBM)/min) and 5 T2D (body fat: 43.4±4.6%, GDR: 6.7±2.5mg/kg LBM/min). Muscle samples were analyzed for pAKT (ser473), AKT, peNOS (ser1177) and eNOS protein and ET‐1 mRNA expression. In response to insulin, peNOS/eNOS was not significantly different between groups (controls: 1.13±0.22, T2D: 0.69±0.31 fold change from baseline; p>0.05). The increase in ET‐1 mRNA from baseline (controls: 1.0±0.4, T2D: 3.4±1.4, p>0.05) was also not different during insulin stimulation (controls: 1.3±0.7, T2D: 2.1±0.9, p>0.05). However, the fold increase of pAKT/AKT to hyperinsulinemia was significantly different between groups (controls: 3.1±0.4, T2D: 1.8±0.4, p=0.002). These initial findings suggest that insulin‐mediated phosphorylation of eNOS protein and induction of ET‐1 mRNA are not significantly different between healthy and T2D individuals.Grant Funding Source: Supported by AHA 12PRE12080242(LJB)
Cardiac volume regulation: transition among two phenotypes in heart failure (1073.2)
Authors: Kerkhof Peter , Li John , Kresh J , Heyndrickx Guy 
Published: June 2021

Background. Guidelines for heart failure (HF) with preserved ejection fraction (pEF) dictate that left ventricular (LV) end‐diastolic pressure > 16 mmHg, EF > 50% and end‐diastolic volume index (EDVI) < 97 mL/m2. Only half of HF patients (pts) present with a classical pattern of reduced EF (rEF). Prevalence of transition from HFpEF to HFrEF reportedly constitutes (either way) as much as 39%. The volume regulation graph (VRG) is explored to theoretically elucidate this occurrence.Methods. LV EDVI and end‐systolic volume index (ESVI) by angiography are analyzed in 48 pts receiving betablockers, with HFpEF (n=35) and HFrEF (n=13) subgroups. Regression analysis for ESVI to EDVI yields VRG. The 2SE ranges and 98% CI limits show potential transition to the complementary territory.Results. For pEF: ESVI = 0.31 EDVI ‐ 2.55, r=0.51 and for rEF: ESVI = 0.66 EDVI ‐ 5.45, r=0.95. The 2SE zones show overlap, suggesting occurrence of transition, especially for 50 < ESVI < 100 mL/m2. An additional group of 44 pts with follow‐up (ranging from 27 to 2385 days) reveals that over time ESVI may decrease by 50% or increase by up to 250%, thus demonstrating LV volumetric plasticity. Notably, about 25% of HFpEF pts can transit to HFrEF territory with a 10% increase in ESVI, while some 40% would convert to HFpEF with a 10% reduction in ESVI.Conclusions. The VRG explains considerable transition from HFrEF to HFpEF and v.v., requiring only a 10% change of ESVI, or roughly a 10% alteration in EF. The novel VRG construct confirms observations from other longitudinal studies.
Enzyme‐linked immunosorbent assay is a viable method for determining release kinetics of cardiac myosin binding protein‐C following isoproterenol‐induced cardiac injury (1073.8)
Authors: Jagadeesan Aravindakshan , Barefield David , Govindan Suresh , Kuster Diederik , Sadayappan Sakthivel 
Published: June 2021

Cardiac myosin binding protein‐C (cMyBP‐C) is shown to be released into the bloodstream following myocardial infarction (MI), suggesting its potential as a biomarker post‐MI. To explore this further, dose‐ and time‐dependent effects on cMyBP‐C release into circulation can be determined following isoproterenol (ISO) administration, an established model of drug‐induced cardiac injury in mice. The objective is to establish a quantitative enzyme‐linked immunosorbent assay (ELISA) that is specific and sensitive in measuring concentrations of cMyBP‐C in serum samples. To determine cMyBP‐C in serum samples following ISO‐induced injury, sandwich ELISA was developed using monoclonal and polyclonal antibodies against cMyBP‐C. To generate a standard graph, cMyBP‐C N’ recombinant peptide (40 kDa) was used to determine inter‐ and intra‐plate coefficient of variability (CV,%), as well as the respective recovery (%) values. The sandwich ELISA assay for quantifying serum concentrations of cMyBP‐C was established with an average lower limit of detection of 0.36 ng/ml and upper limit of detection up to 2000 ng/ml, indicating the assay can detect cMyBP‐C within the working range of our experiment. Furthermore, an inter‐ and intra‐plate variability of 4.7% and 4.2%, respectively, suggests a reproducible assay. The average inter‐ and intra‐plate recoveries were, 101% and 103%, illustrating the accuracy of the assay in measuring cMyBP‐C concentration. Using this assay, future experiments will be conducted to measure the exact amount of cMyBP‐C in the mice serum post‐cardiac injury.Grant Funding Source: American Physiological Society ‐ Undergraduate Summer Research Fellowship
Comparative assay of oxidative stress biomarkers on normotensive and hypertensive, pre‐menopausal and postmenopausal women: a pilot study (1074.8)
Authors: Calzada‐Frías Jesús , Lugo‐Martínez Gabriela , Jiménez‐Zamarripa Carlos , Ocharán‐Hernandez María , Cariño‐Cortés Raquel , Calzada‐Mendoza Claudia 
Published: June 2021

Introduction: Menopause is defined as the cessation of menstruation for one year in raw, due to ovarian dysfunction, which decreases the production of estrogen. During this stage, several pathologies can be developed, such as hypertension which is associated to oxidative stress, then, there are two risk factors to participate on cardiovascular diseases.Currently, knowledge of factor present in postmenopause in relationship to cardiovascular diseases can help to propose therapeutic guides to reduce them.Objective: To analyze the association between oxidative stress on pre‐menopausal and postmenopausal women with hypertension.Methods: In the present study were included fifty six divided in four groups: a) normotensive‐premenopausal, b) hypertensive‐premenopausal, c) normotensive‐postmenopausal and d) hypertensive‐postmenopausal. Menopause was corroborated by clinical evaluation. On the other hand, oxidative stress biomarkers analyzed, were a) malondyaldehyde (MDA) for lipid oxidation, carbonyl group for protein oxidation and antioxidant defense was evaluated by determination of carbonyl and sulfhydryl group, respectively; anthropometric evaluation was evaluated too.Results: Women included were classified according to their status (normotensive or hypertensive, pre‐menopausal or postmenopausal) which was corroborated by medical history. The MDA concentration was lower in normotensive premenopausal; with respect protein damage, all groups presented similar levels, finally, postmenopausal women had lower antioxidant defense. On the other hand, in anthropometry evaluation, only body mass index was (BMI) higher in hypertensive‐premenopausal than on the other groups, while in determinations such as wais‐hip ratio, systolic and dyastolic blood pressures, were similar.Conclusion: Oxidative stress is increased in hypertensive postmenopausal women and BMI is related to high blood pressure in in hypertensive‐premenopausal women.
Increased memory and decreased naïve T cells in human hypertension (1074.9)
Authors: Marvar Paul , Cruise Tom , Hart Emma , Burchell Amy , Ratcliffe Laura , Nightingale Angus , Paton Julian 
Published: June 2021

Studies have revealed a role for pro‐inflammatory effector‐like CD3+ T cells in the pathogenesis of experimental hypertension. Despite these observations, our knowledge of the role that T cells and subsets of T cells (memory vs naïve) play in the development of human hypertension is unknown. We hypothesized that circulating cells of hypertensive patients exhibit a pro‐inflammatory T cell phenotype, as determined by the balance of memory (effector) versus naïve CD3+ cells. Using flow cytometry, subsets of circulating T cells and markers of antigenic memory were analyzed in male hypertensive patients and normotensive subjects. There were no differences in the overall percentage of CD3+ cells in normotensive (63.3 ± 3.7%) (n=5; mean age 34 yrs; mean systolic BP 128.6 mmHg) vs. hypertensive men (62.2 ± 5.5%) (n=6; mean age 53.5 yrs; mean systolic BP 154.7 mmHg). The percentage of CD4+ and CD8+ T cell subsets were not statistically different between groups. Further subset analysis revealed that the ratio (1.6 ± 0.3 vs 0.7 ± 0.1; P <0.05) of memory (CD45RO+CD3+) vs. naïve (CD45RA+CD3+) T cells as well as the percentage of CD8+CD62L(low) cells (70.4 ± 4.5 vs 52.8 ± 6.3; P <0.05) were increased in hypertension. These results demonstrate an imbalance in effector memory / naïve T cells in hypertensive men and provide further evidence that chronic antigen exposure may be involved in the pathogenesis of hypertension. Supported by NIH‐HL107675‐01, Marie Curie‐IIF ‐ 276147 and British Heart Foundation.Grant Funding Source: NIH‐HL107675‐01, Marie Curie‐IIF – 276147 and British Heart Foundation