bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Reactivity of Basilar and Circle of Willis Arteries in Osteoarthritis and Ischemic Heart Disease Patients
Authors: Al‐Khazraji Baraa K. , Badrov Mark B. , Vording Jennifer L. , Birmingham Trevor B. , Shoemaker J. Kevin 
Published: November 2023

Regional brain perfusion is supplied by flow from subcortical conduit vessels, namely the anterior, middle and cerebral arteries, and the functionality of these vessels is largely characterized by vasoreactivity to physiological stimuli. Patients with cardiovascular disease, such as ischemic heart disease (IHD), are at greater risk for stroke, a risk determined in part by cerebrovasoreactivity tests (i.e., dilation or constriction). Patients with osteoarthritis (OA) express greater incidence of cardiovascular disease. However, whether these patients express impaired cerebrovascular reactivity, and how such changes are manifest in each subcortical conduit vessel, remain unanswered. This study tested the hypothesis that, compared to healthy individuals (CTL), those either IHD or OA exhibit heterogeneous yet impaired reactivity (change in cross‐sectional area, ΔCSA) in the basilar and all Circle of Willis conduit in response to elevated levels of end‐tidal CO2 (ETCO2). In 22 participants (CTL: 6, OA: 7, IHD: 9; age range: 40–75 years), we collected simultaneous subcortical vascular responses (i.e., vasoreactivity) during normocapnia and hypercapnia (gas mixture of 5% CO2, 95% oxygen; ADInstruments Powerlab) conditions using a 3 Tesla Siemens MAGNETOM Fit scanner and T1‐weighted pulse sequence (0.7 mm isotropic). The relative change in cross‐sectional area (%ΔCSA) in response to CO2, measured at a site perpendicular to the direction of flow, of the basilar, left and right internal carotid, anterior, middle, and posterior cerebral arteries (9 vessels total) were measured using OsiriX software. The cross‐sectional vasoreactivity to changes in ETCO2 (ΔETCO2) was calculated as %ΔCSA/ΔETCO2. In all 9 vessels, OA and IHD patients exhibited similar vasoreactivity; yet, relative to CTL, OA and IHD patients had lower reactivity (%/mm Hg; mean ± S.D.) in the right anterior cerebral (CTL: 16.3 ± 6.5, OA: 3.8 ± 4.1, IHD: 4.4 ± 9.4; p<0.05), right internal carotid (CTL: 8.9 ± 4.9, OA: 3.9 ± 2.9, IHD: 1.5 ± 1.5; p<0.05), and basilar arteries (CTL: 7.8 ± 4.6, OA: 0.7 ± 0.8, IHD: 2.9 ± 3.0; p<0.05). Additionally, relative to CTL, OA patients expressed less left anterior cerebral artery reactivity (CTL: 11.6 ± 6.5, OA: 2.3 ± 1.2, IHD: 3.5 ± 8.3; p<0.05), and IHD patients had diminished right middle cerebral artery reactivity (CTL: 22.4 ± 17.4, OA: 5.6 ± 6.4, IHD: 3.7 ± 4.8; p<0.05). Therefore, heterogeneous patterns of dilation across subcortical vessels was observed in all groups, but the patient groups exhibited significantly impaired vasoreactivity in many of these vessels compared to healthy individuals.Support or Funding InformationSupported by The University of Western Ontario Bone and Joint Institute Catalyst grant and the Canadian Institute of Health Research grant (201503MOP‐342412‐MOV‐CEEA).
ATP‐Sensitive Potassium Channels Contribute to Progressive Coronary Vasodilation in Response to Acute Isovolemic Hemodilution
Authors: Kiel Alexander M , Goodwill Adam G , Barnard April L , Sturek Joshua T , Noblet Jillian N , Sassoon Daniel J , Tune Johnathan D 
Published: November 2023

This study was designed to identify mechanisms responsible for coronary vasodilation in response to progressive decreases in arterial oxygen content. Isovolemic hemodilution was produced in open‐chest, anesthetized swine via concurrent removal of 500 ml of arterial blood and the addition of 500 ml of 37°C synthetic plasma expander (Hespan, 6% hetastarch in 0.9% sodium chloride) up to a total sequential volume exchange of 4.02 ± 0.19 L. Arterial blood pressure, heart rate, left anterior descending coronary blood flow, and coronary arterial and venous blood gases were measured following stabilization after each fluid exchange. To establish content dependent effects, data were analyzed based on binned arterial oxygen contents of 18.0–13.0, 12.9–10.0, 9.9–8.0, 7.9–6.0, 5.9–4.0 ml O2/dl. Despite eliciting no change in mean arterial pressure, heart rate, or myocardial oxygen consumption, progressive hemodilution demonstrated clear reductions in arterial oxygen content (14.7 ± 0.4 to 4.7 ± 0.1 ml O2/dl; P < 0.001) and hematocrit (32 ± 1 to 10 ± 1%; P < 0.001). An accompanying increase in coronary flow was observed (0.39 ± 0.05 to 1.63 ± 0.16 ml/min/g; P < 0.001) which was sufficient to maintain oxygen delivery (58 ± 7 to 76 ± 8 μl O2/min/g; P = 0.46). Inhibition of nitric oxide synthase (L‐NAME: 25 mg/kg, iv) resulted in significant increases in mean arterial pressure (87 ± 2 to 122 ± 3 mmHg; P < 0.001) and myocardial oxygen consumption (47 ± 2 to 57 ± 3 μl O2/min/g; P < 0.001), however, this treatment did not significantly alter the coronary response to progressive anemia (P = 0.41). Inhibition of KV channels (4‐aminopyridine: 0.3 mg/kg, iv) also did not significantly alter coronary responses to decreasing arterial oxygen content. Alternatively, blockade of KATP channels with glibenclamide (3 mg/kg, iv) significantly reduced the coronary blood flow response from 1.87 ± 0.11 ml/min/g to 1.12 ± 0.08 ml/min/g (P < 0.001) when arterial oxygen content was lowered from 15.1 ± 0.3 to 4.7 ± 0.1 ml O2/dl. This glibenclamide‐induced decrease in coronary flow diminished myocardial oxygen delivery from 69.4 ± 4.3 to 52.0 ± 4.3 μl O2/min/g (P < 0.001). Taken together, these data support that KATP channels, but not KV channels or nitric oxide, contribute to coronary vasodilation in response to progressive, acute isovolemic hemodilution.Support or Funding InformationThis study was supported by U01HL118738 and the Purdue University Ross Fellowship. Ms. Noblet was supported by TL1 TR000162 (A. Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.
Traumatic brain injury impairs myogenic constriction of cerebral arteries: role of mitochondria‐derived H2O2, TRPV4 and calcium‐activated potassium channels
Authors: Szarka Nikolett , Pabbidi Mallikarjuna R. , Amrein Krisztina , Czeiter Endre , Pohoczky Krisztina , Helyes Zsuzsanna , Ungvari Zoltan , Buki Andras , Koller Akos , Toth Peter J 
Published: November 2023

Traumatic brain injury (TBI) impairs pressure‐induced myogenic constriction of cerebral arteries, which contributes to TBI‐related autoregulatory dysfunction and the development of secondary brain injury. TBI has been shown to lead to mitochondrial oxidative stress in cerebral vessels, which likely contributes to secondary brain injury, as well. We tested the hypothesis that TBI‐induced mitochondrial oxidative stress contributes to the impaired myogenic response of cerebral arteries after TBI and aimed to establish the underlying mechanisms. We induced traumatic brain injury in WKY rats using the weight‐drop technique, and 24 hours after severe TBI we found that myogenic responses of isolated middle cerebral arteries (MCAs) of TBI rats were blunted compared to control. The impaired myogenic responses of MCAs were restored after inhibiting mitochondrial oxidative stress (mitoTEMPO), eliminating H2O2 (PEG catalase) and blocking large‐conductance calcium‐activated potassium (BKCa) channels and transient receptor activated vanilloid channel 4 (TRPV4). We also found that H2O2‐induced dilation of MCAs involves the activation of BKCa and TRPV4 channels, and that H2O2‐induced BK currents on vascular smooth muscle cells depend on the activation of TRPV4 channels. Our results suggest that after TBI excessive mitochondria‐derived H2O2 activates BKCa channels via TRPV4 channel activation in the cerebrovascular wall, which diminishes pressure‐induced constriction of cerebral vessels. Future studies should elucidate the potential of inhibiting these vascular pathways to restore autoregulatory function after TBI in order to prevent TBI‐related secondary brain damage in patients suffered traumatic brain injury.Support or Funding InformationThis work was supported by grants from the Marie Curie Actions SMARTER 7th Framework Program of the European Union 606998 (to NSz and AK), the Hungarian Academy of Sciences (the Bolyai Research Scholarship BO/00634/15 to PT), the Hungarian Brain Research Program (Grant No. KTIA_13_NAP‐A‐II/8 to PT, ECz and AB), National Center for Complementary and Alternative Medicine (R01‐AT006526 to ZU) and the Hungarian Scientific Research Fund (K108444 to AK).
An Automated, Label‐free Method for Quantifying Intercellular Gap Formation in Images of Cell Monolayers
Authors: Francis Christopher Michael , Morrow Kyle Adam , Renema Phoibe , Teague Douglas Alex , Agwaramgbo Ezinne , Langham Geri , Stevens Trevor C , Williams Chris Caesar , Alvarez Diego F , Audia Jonathon P , Balczon Ronald D , Stevens Troy 
Published: November 2023

Within cell monolayers, specifically the vascular endothelium, intercellular gap formation is an important phenomenon involved in response to infection, wound healing, force transduction, and barrier regulation. Because intercellular gap formation is studied extensively in the context of biological research, there exists a need for analysis tools that enable the quantification of intercellular gaps. However, existing tools to assess cell gaps are limited by the requirement of exogenous cell markers and fluorescent probes to label cellular regions, or by cell damage‐associated markers that incompletely reflect the dynamic process of physiological gap formation and repair. Currently, there is no method of quantifying intercellular gaps in unlabeled light micrographs. Therefore, we developed an automated, algorithmic solution to the quantification of cell gaps, which works by iterative contrasting of cellular and non‐cellular regions within images. We vetted this algorithm by analyzing dose‐dependent cytotoxicity responses in pulmonary microvascular endothelial cell (PMVEC) monolayers after Pseudomonas aeruginosa infection, and compared our data to the conventional lactate dehydrogenase (LDH) cell cytotoxicity assay. We found that our algorithm was comparably sensitive to the LDH assay. However, it was faster and required no additional reagents. Additionally, our approach eliminated the user bias inherent to manual analysis techniques, and was robust to deviations in image background intensity, color, blur, and cell morphology. We conclude that this novel technique represents an accurate and sensitive approach to the measurement of intercellular gap formation. We next plan to develop and implement a user interface in order to disseminate this technology to the scientific community at large.Support or Funding InformationSupported by NIH HL66299 and NIH HL60024.
Racial Differences in Cell Adhesion Molecule Expression in HUVECs
Authors: Adeyemo Adelola , Ling Chenyi , Cook Marc D. , Grimm Heather , Brown Michael D. 
Published: November 2023

BackgroundEndothelial dysfunction is both a root cause and consequence of hypertension (HTN) and cardiovascular diseases (CVD). It is characterized by nitric oxide (NO) deficiency and altered release of vasoactive substances including inflammatory cytokines and adhesion molecules. African Americans (AAs) have higher rates of these vascular disruptions and develop hypertension at higher rates than any other racial/ethnic group in the United States. C‐Reactive Protein (CRP) levels are greater in AAs and CRP has been shown, in vitro, to promote endothelial dysfunction.PurposeTherefore, we examined the impact of CRP stimulation on AA and Caucasian (CA) endothelial cell (EC) activation.METHODSCRP with and without receptor blockade (IgG) was applied to confluent ECs. Gene and protein expression of FcγRIIB receptor, Intracellular Adhesion Molecule‐1 (ICAM‐1), and Vascular Cell Adhesion Molecule‐1 (VCAM‐1) was assessed. HUVECs were pretreated with CRP receptor FcγRIIB antibodies for additional inhibitory experiments.RESULTSCRP significantly upregulated VCAM‐1 and ICAM‐1 gene and protein (>0.5 fold increase, p< .01) expression. Significant racial differences in VCAM‐1 protein were only seen under CRP incubation at 10 μg/mL (0.25 fold difference, p< .005; Fig 3). Strong racial differences in ICAM‐1 gene expression existed within all conditions (p< .05; Fig 2), but CRP significantly increased ICAM‐1 expression in AA HUVECs but not CA. Blockade of the CRP FcγRIIB receptor decreased the relative CRP‐induced differences in VCAM‐1 and ICAM‐1 between AA and CA HUVECs (p< .05; Fig 1). However, ICAM‐1 remained significantly elevated in AA. FcγRIIB receptor gene expression was significantly greater in AA compared to CA HUVECs under basal and CRP conditions (p< .01; Fig 4).CONCLUSIONCA and AA HUVECs respond differently to CRP, with AA HUVECs showing greater inflammatory adhesion molecule upregulation under basal and stimulated conditions. Elevated levels of adhesion molecules likely contribute to increased CVD risk in AAs considering the higher circulating CRP levels and the greater endothelial responses to CRP.Support or Funding InformationACSM Doctoral Student Research Grant to Chenyi Ling
Repeated Sprint Training in Hypoxia Improves Exercise Tolerance in Recreationally‐ Trained Men: A Randomized Single‐Blind Study
Authors: Wang Ran , Fukuda David H. , La Monica Michael B. , Starling Tristan M. , Stout Jeffrey R. , Hoffman Jay R. 
Published: November 2023

PurposeAs a novel altitude training approach, repeated sprint training in hypoxia (RSH) is based on repetition of “all‐out” efforts of short duration separated by incomplete recovery. Although several investigations have reported that RSH provides additional benefits when compared with the same training under normoxia (RSN), the data regarding the effect of RSH on exercise tolerance is limited. Therefore, the primary purpose of this study was to investigate the effect of RSH on exercise tolerance in recreationally‐trained men.MethodsTwenty‐six recreationally‐trained men (22.9 ± 3.1 y, 1.75 ± 0.76 m, 76.0 ± 9.3 kg) performed 8 sessions of repeated sprint training (each consisting of 3 sets of 5 × 10‐s sprints at a resistance of 7.5% of body mass, with 20‐s intervals of recovery) over 4 weeks (2 sessions per week) on a cycle ergometer either in normoxia (RSN, 300 m; FiO2 = 20.9%; n = 13) or normobaric hypoxia (RSH, 3000 m; FiO2 = 14.2%; n = 13). Anthropometry, graded exercise testing (GXT), repeated sprint testing (RST), and 3‐min all‐out critical power testing (3MT) was performed in normoxic conditions prior to and after completion of training. Changes in body composition, GXT peak power, maximal oxygen consumption (VO2max), respiratory compensation point (RCP), power output at RCP, mean power of all 5 sprints and the 5th sprint in RST, 3MT critical power and total work between RSH and RSN were compared using one‐way analysis of covariance (ANCOVA) on post‐test values with pre‐test values serving as the covariate.ResultsNo group differences were observed in body composition (p = 0.502), GXT peak power (p = 0.170), VO2max (p = 0.124), and mean power of all 5 sprints in RST (p = 0.151), while significantly greater mean power of the 5th sprint in RST (p = 0.036, 8.655 vs 8.209 W· kg−1), 3MT critical power (p = 0.027, 2.829 vs 2.625 W· kg−1) and total work (p = 0.011, 0.741 vs 0.706 kJ· kg−1) were detected in RSH as compared to RSN. Additionally, a significantly greater improvement was found only in RCP (p = 0.019, 38.965 vs 36.173 ml· kg−1· min−1) following RSH. Though not significant, a trend towards a greater improvement was noted in power output at RCP (p = 0.076, 2.929 vs 2.806 W· kg−1).ConclusionThe present findings demonstrate that greater improvement in exercise tolerance, together with enhanced working capacity, can be attained with RSH compared with RSN.Support or Funding InformationThis study was partially funded by a National Strength and Conditioning Association (NSCA) International Collaboration Grant.
COMBINED EXERCISE TRAINING (AEROBIC PLUS RESISTANCE) PROMOTES ADDITIONAL CARDIOVASCULAR BENEFITS IN RELATION TO AEROBIC OR RESISTANCE ALONE IN EXPERIMENTAL MODEL OF MENOPAUSE
Authors: Sanches Iris Callado , dos Santos Costa Gabrielly Minguta , Freitas Sarah Cristina , Bernardes Nathalia , Doro Marcio , Irigoyen Maria‐Cláudia , De Angelis Kátia 
Published: November 2023

IntroductionThe cardiovascular benefits of exercise training (ET) after menopause are mainly due to the aerobic training, getting to doubt whether the association of aerobic with resistance exercise could bring different effects.ObjectivesTo compare the effects of aerobic, resistance and combined (aerobic + resistance) exercise training on hemodynamic parameters and baroreflex sensitivity in an experimental model of menopause.MethodsFor this, 35 female Wistar rats (200–220g) were divided into (n=7 each group): 1 sedentary control group (C); and 4 ovariectomized groups (bilateral removal of ovaries): sedentary (SO), underwent to aerobic (AET), resistance (RET) and to combined ET (CET). After 8 weeks of ET, the animals were cannulated in the carotid artery for direct recording of arterial pressure (AP) (CODAS, 2kHz). Increasing doses of phenylephrine and sodium nitroprusside were used to test the baroreflex sensitivity (BS).ResultsThe ovarian hormone deprivation induced an increase in mean AP (MAP) in the SO group (119.8±2.5 vs. 114.5±1.5 mmHg in C) associated with reduced BS for both tachycardic responses (TR) (2.67±0.55 vs. 4.29±0.41 bpm/mmHg in C) and for bradycardic responses (BR) (−0.61±0.36 vs. −1.17±0.16 bpm/mmHg in C). All trained animals presented a normalization of MAP (AET: 111.7±1.5, RET: 108.9±2.4, CET: 107.6±3.0 mmHg vs. SO), which was associated with reduction of diastolic AP (vs. SO). The group underwent to combined ET presented a reduction in systolic AP compared with the other groups (CET: 115.7±2.3 vs. C: 131.6±2.1; SO: 135.5±3.8, AET: 130.9±1.8; RET: 131.9±2.6 mmHg). The trained groups showed normalization of baroreflex sensitivity for BR (AET: −0.97±0.16; RET: −1.29±0.20; CET: −1.34±0.04 vs. SO), and only resistance ET was not able to normalize RT (AET: 4.12±21; RET: 3.59±0.62; CET: 3.95±0.38 bpm/mmHg vs. SO). All trained groups showed resting bradycardia (C: 368.4±5.5; SO: 382.9±8.9; AET: 335.5±6.9; RET: 353.0±8.2; CET: 345.7±8.1 vs. SO: 382.9 ± 8.9 bpm).ConclusionsThe 3 modalities of ET were effective in cardiovascular improvement after ovarian hormone deprivation. However, the combined ET promoted additional benefits in relation to aerobic ET (reduction in SAP) and resistance ET (improved baroreflex sensitivity ‐ TR) isolated.
The Effect of Protease‐Activated Receptor 2 on Cutaneous Vasodilation and Sweating in Young Males During Exercise in the Heat
Authors: Halili Lyra , Danquah Mercy , Fujii Naoto , McNeely Brendan , Kenny Glen 
Published: November 2023

Protease‐activated receptor 2 (PAR‐2) is a G protein‐coupled receptor stimulated by the enzyme trypsin and is responsible for modulating the inflammatory response. It has been localized ‐on both the eccrine sweat glands and cutaneous vascular endothelial cells. In particular, activation of PAR‐2 contributes to the degranulation of secretory cells in the eccrine sweat glands and may therefore play a role in modulating the sweating response in humans. However, it is unknown if activation of PAR‐2 augments cutaneous vasodilation and sweating during exercise in the heat. Therefore, the purpose of the present study was to investigate these heat loss responses in young adults exercising in the heat. Five healthy, habitually active, young males (25 ± 6 years) performed 50‐min of moderate intensity (~55% VO2peak) cycling in the heat (35°C, 20% relative humidity) followed by a 30‐min recovery period. Local forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC, laser‐Doppler perfusion units/mean arterial pressure) were recorded at four skin sites, continuously perfused with: 1) Lactated Ringer's (Control), 2) 0.05 mM, 3) 0.5 mM, or 4) 5 mM SLIGKV‐NH2 (PAR‐2 agonist) via intradermal microdialysis. There were two baseline measurements conducted at different ambient temperatures. The first baseline (Baseline 1) was measured at 25°C, 20% relative humidity and the second baseline (Baseline 2) depicted the onset of heat stress and was measured at 35°C, 20% relative humidity. During Baseline 1, there was a tendency for an increase in CVC at both the 0.5 mM (14 ± 3% CVCmax, P = 0.078) and 5 mM (21 ± 7% CVCmax, P = 0.067) SLIGKV‐NH2 site relative to Control. At the end of the 50‐min exercise bout, there were no significant differences in CVC between all sites (Control: 71 ± 4% CVCmax; 0.05 mM: 69 ± 8% CVC max; 0.5 mM: 68 ± 5% CVCmax; 5 mM: 74 ± 9% CVCmax; P > 0.05) Further, we also show that activation of PAR‐2 at all concentrations of SLIGKV‐NH2 did not elicit significant changes in sweat rate at the end of exercise (Control: 1.31 ± 0.24; 0.05 mM: 1.52 ± 0.21; 0.5 mM: 1.55 ± 0.12; 5 mM: 1.51 ± 0.13 mg·min−1·cm−2; P > 0.05). In summary, our preliminary findings demonstrate that PAR‐2 activation exhibits a tendency to increase CVC at higher concentrations (0.5 and 5 mM) of SLIGKV‐NH2 relative to Control during baseline conditions. However, this increase is not present at the onset of and during heat stress, thereby indicating that PAR‐2 does not contribute to the modulation of sweating and cutaneous vasodilation during moderate intensity exercise in the heat.Support or Funding InformationThis study was supported by the Natural Sciences and Engineering Research Council of Canada (Discovery grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).
Carotid Chemoreceptor Control of Muscle Sympathetic Nerve Activity in Hypobaric Hypoxia
Authors: Fisher James P , Flück Daniela , Hilty Matthias P , Lundby Carsten 
Published: November 2023

High altitude hypoxia causes sympathoexcitation in humans, but the underlying mechanisms remain unclear. In this study we tested the hypothesis that muscle sympathetic nerve activity (MSNA) would be lowered at high altitude when carotid chemoreceptor activity is reduced by intravenous dopamine infusion.Nine healthy individuals (mean [SD]; 26 [4] yr, 179 [9] cm, 75 [10] kg, 1 women) were studied at sea level (Zurich) and at the Jungfraujoch research station (3454 m), 15–17 days after arrival. Intravenous infusions of a placebo (saline) and dopamine (3 μg/(kg*min)) were administered on both study days, according to a single blind design. Minute ventilation (VE) and the partial pressure of end‐tidal oxygen (PETO2) and carbon dioxide (PETCO2) were measured breath‐by‐breath (Cosmed). Mean arterial pressure (MAP), cardiac output (CO) and total peripheral resistance (TPR) were recorded on a beat‐to‐beat basis via finger photoplethysmography (Nexfin) and multi‐unit recordings of MSNA were obtained using peroneal microneurography (ADInstruments).Sojourn to high altitude decreased PETO2 (mean±SE; saline, 93±1 to 60±1; dopamine, 91±1 to 57±1 mmHg), PETCO2 (saline, 40±1 to 31±0.4; dopamine, 41±1 to 32±1 mmHg) and increased VE (saline, 8.6±0.5 to 11.3±0.6; dopamine, 8.2±0.5 to 10.6±0.8 L· min−1) (P<0.05). MAP (saline, 82±4 to 91±3; dopamine, 82±4 to 91±3 mmHg) and MSNA burst frequency (saline, 16±3 to 28±4; dopamine, 16±4 to 31±4 bursts· min−1) were also increased at altitude, while CO (saline, 7.4±0.5 to 7.7±0.4; dopamine, 8.3±0.5 to 8.3±0.3 L· min−1) was unchanged, and TPR was decreased (saline, 15.1±1 to 14.7±1; dopamine, 14.7±1 to 12.7±1 L· min−1) (P<0.05). Dopamine infusion increased CO, decreased TPR, but had no effect on either MAP or MSNA burst frequency (P<0.05).These data suggest that high altitude‐mediated increases in MSNA are not attributable to a dopaminergic mechanism.