bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiodynamic Associations With Mental Health And Resilience In Undergraduate Students
Authors: Knetsch Rachel , Klassen Stephen A. , Shoemaker J. Kevin 
Published: June 2021

The 2016 National College Health Assessment (NCHA) indicates a majority of Canadian students reported feeling overwhelmed, stressed, and anxious during their undergraduate studies, which lead to poorer academic performance. Heart rate variability (HRV), the variation in time between consecutive heart beats, is indicative of the inherent flexibility of a healthy autonomic nervous system. While autonomic indices, in the form of HRV, have been used to describe chronic physiological stress, the role of HRV as a physiological index of mental health remains unclear. Furthermore, HRV monitoring may provide a quantitative means for interpreting the gradation of stress and anxiety experienced by undergraduate students. The objective of this study was to analyze the relationship between cardiac autonomic control and mental health scores in undergraduate students. Seventy‐seven healthy undergraduate students (18–24 years of age, 17 males; Western University, Canada) wore a Firstbeat Bodyguard® device for a 24‐hour period while continuing with day‐to‐day activities. Sleep R‐R interval data were isolated, and the root mean square of successive differences (RMSSD; Firstbeat® software) was calculated. Students also completed the brief resilience scale (BRS), generalized anxiety disorder 7‐item scale (GAD‐7), and the mental health inventory (MHI) questionnaires. Regression analysis established the predictive relationship between RMSSD and the psychological survey scores for this sample. The RMSSD index correlated positively with BRS (r=0.30, p<0.01). The RMSSD index correlated negatively with GAD‐7 scores (r=−0.27, p<0.05). The RMSSD index did not correlate with MHI scores. These data suggest that higher HRV may indicate greater psychological resilience, and lower anxiety amongst undergraduate students.Support or Funding InformationWestern University Interdisciplinary Initiative ProgramThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sympathoexcitatory role for neurons projecting from the mesencephalic locomotor region to the rostral ventrolateral medulla in rats
Authors: Koba Satoshi , Kumada Nao , Hanai Eri , Kataoka Naoya , Nakamura Kazuhiro , Watanabe Tatsuo 
Published: June 2021

C1 neurons in the rostral ventrolateral medulla (RVLM) are reportedly excited by voluntary exercise. The present study aimed to explore neural pathway(s) upstream to the RVLM that can play a role in sympathetic adjustments to exercise. First, via neuronal tracing experiments, we found that rat mesencephalic locomotor region (MLR), in which cholinergic neurons are abundantly distributed, sends direct projections to the RVLM (MLR‐RVLM neurons) since the MLR contained a number of neuronal cells immunoreactive to cholera toxin subunit B (CTb) that had been injected into the RVLM in advance (n = 8). It is noted that very few neurons immunoreactive to choline acetyltransferase in the MLR were labeled with CTb (n = 3), suggesting that the MLR‐RVLM neurons are not cholinergic. Next, we found that optogenetic stimulation of MLR‐RVLM neurons causes sympathoexcitation in rats. An AAV vector that encodes the channelrhodopsin variant, ChIEF‐tdTomato was bilaterally microinjected into the MLR (n = 7). More than 3 weeks later, bilateral photostimulation (473 nm wavelength, 10 mW, 40 Hz) provided to the RVLM of the anesthetized rats significantly (P < 0.05) elevated blood pressure. In another set of rats (n = 3), a retrograde AAV vector that encodes the channelrhodopsin‐GFP was bilaterally microinjected to the RVLM. In these rats, bilateral photostimulation of the MLR, in which a number of GFP‐labeled cell bodies were confirmed, significantly increased renal sympathetic nerve activity and blood pressure. Finally, confocal imaging revealed that MLR‐derived, tdTomato‐labeled axons containing VGLUT2 were closely associated with tyrosine hydroxylase‐positive neurons in the RVLM, suggesting that MLR‐RVLM glutamatergic neurons form synaptic contacts with RVLM C1 neurons. Based on these observations, we propose that excitation of MLR‐RVLM glutamatergic neurons contribute to sympathetic adjustments to exercise via stimulation of RVLM C1 neurons.Support or Funding InformationThis study was supported by JSPS KAKENHI 15H05367 (SK) & 16K15190 (SK); 16H05128 & 15H05932 (KN).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Contralateral Forearm Somatosensory Stimulation on Heart Rate Responses to Isometric Hand Grip Exercise
Authors: Smith Sydney Olivia , Woehrle Emilie , Klassen Stephen Alexander , Jacobs Kaitlyn Grace , Knetsch Rachel , Shoemaker J. Kevin 
Published: June 2021

BackgroundVagal withdrawal forms the dominant mechanism determining the rapid heart rate (HR) response at the onset of moderate intensity isometric handgrip (IHG) exercise. Previous evidence suggested that the addition of submotor somatosensory stimulation (STIM) can elevate vagal cardiac function in some individuals. This study tested the hypothesis that STIM can interfere with the vagal withdrawal and HR responses at the exercise onset.MethodsYoung healthy individuals (n=7, ages 24 ± 1.2 years) were recruited. STIM was provided by transcutaneous electrical nerve stimulation (TENS; 100 Hz, 50 μs) on the medial forearm through anesthetized skin. A 3‐lead ECG provided R‐R interval data. Participants performed 2–3 trials of IHG at 35–40% maximal voluntary contraction, each lasting 20 seconds and separated by one minute of rest. These were performed both with and without STIM and baseline cardiovagal influence was modified by repeating the tests in seated and supine positions using a varied order of STIM delivery.ResultsIHG elicited increased HR in each posture (supine: baseline=64 ± 9 bpm, IHG=73 ± 7 bpm; p<0.05; seated: baseline=66 ± 6 bpm, IHG=78 ± 8 bpm, p<0.05). In the seated position, STIM reduced the maximum HR response to IHG, compared to no STIM, in five out of seven participants resulting in an overall modest effect (no STIM: 19 ± 10 bpm; STIM: 15 ± 8 bpm; p<0.05; d=0.44). In the supine position, however, the effect of STIM to reduce the HR response was observed in only three out of seven participants. Thus, there was no significant difference between treatments (no STIM: 15 ± 7 bpm; STIM: 16 ± 9 bpm; p>0.05; d=0.12).ConclusionThese data suggests that the HR response to exercise in young healthy adults can be modulated with submotor somatosensory nerve stimulation but that this effect is most apparent in the seated position.Support or Funding InformationSupported by Natural Sciences and Engineering Research Council of CanadaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Loss of Hypoxia Inducible Factor‐1α Increases Right Ventricular Hypertrophy in Chronic Hypoxia‐Induced Pulmonary Hypertension
Authors: Smith Kimberly A. , Waypa Gregory B. , Dudley V. Joseph , Schumacker Paul T. 
Published: June 2021

Pulmonary hypertension (PH) is a risk factor for right ventricular (RV) hypertrophy and right heart failure in patients with congenital heart disease, chronic obstructive pulmonary disease, interstitial lung diseases, and obstructive sleep apnea. Chronic alveolar hypoxia (CH) in these diseases promotes sustained pulmonary vasoconstriction and pulmonary artery (PA) remodeling resulting in the development of PH. Patient outcome, however, is often determined by the response of the RV to increased afterload caused by increased PA resistance. Little is known about the cellular and molecular mechanisms involved in RV hypertrophy associated with PH, which begins as compensated hypertrophy but can progress to dilated, decompensated RV failure, and death. Recently, we have shown that loss of hypoxia inducible factor 1 alpha (HIF‐1α) in PA smooth muscle cell (PASMC) attenuates PA remodeling and the increase in RV systolic pressure (RVSP) induced by CH but fails to attenuate RV remodeling. This suggests that CH directly regulates RV remodeling independently from PH and increased RVSP. Therefore, we aimed to determine the role of HIF‐1α in RV remodeling in CH‐induced PH. Genetic deletion of HIF‐1α from smooth muscle (SM) was achieved by breeding SM‐heavy myosin chain‐Cre expressing mice (SMC) with HIF‐1αflox/flox mice to generate SMC‐HIF‐1αflox/flox mice. Genetic deletion of HIF‐1α from cardiomyocytes was achieved by breeding cardiac‐specific alpha myosin‐heavy chain‐Cre expressing mice (Myh6Cre) with HIF‐1αflox/flox mice to generate Myh6Cre‐HIF‐1αflox/flox mice. A double SM and cardiomyocyte knockout was also generated by crossing SMC‐HIF‐1αflox/flox with Myh6Cre‐HIF‐1αflox/flox mice to generate SMC‐Myh6Cre‐HIF‐1αflox/flox mice. Tamoxifen was administered i.p. to activate Cre‐mediated excision of the HIF‐1α gene in targeted cells of adult mice. Wildtype, SMC‐, Myh6Cre‐ and SMC‐Myh6Cre‐HIF‐1α‐depleted mice were then housed under normoxia or CH (10% O2) for four weeks. CH increased RVSP and RV remodeling in wildtype mice. Loss of HIF‐1α in SMC‐HIF‐1α or SMC‐Myh6Cre‐HIF‐1α attenuated the CH‐induced increase in RVSP, but did not alter RV remodeling. Interestingly, the deletion of HIF‐1α from cardiomyocytes (Myh6Cre‐HIF‐1α) increased RV hypertrophy compared to wildtype mice in CH while having no effect on RVSP. These data suggest that HIF‐1α regulates RV remodeling and that loss of HIF‐α in cardiomyocytes results in unregulated cardiac remodeling during CH. Understanding the role of HIF‐1α in RV remodeling in PH may provide therapeutic targets for the development of improved treatment strategies for patients with PH.Support or Funding InformationSupported by NIH Grants HL35440 and HL122062 (PTS) and Parker B. Francis Fellowship (KAS)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sildenafil Abolishes Pulmonary Hypertension Induced by Left Heart Pressure Overload in Rats
Authors: Chovanec Milan , Al‐Hiti Hikmet , Kaftanova Barbora , Durisova Jana , Hampl Vaclav , Herget Jan 
Published: June 2021

Pulmonary hypertension (PH) induced by pressure overload of the left heart has recently attracted increasing attention in clinical practice. Unfortunately, no specific treatment of PH is approved for this group of patients. We previously described a simple rodent model of this condition. In this study, we used it to test a hypothesis that sildenafil can be beneficial in this type of PH. Left heart pressure overload was induced in adult male Wistar rats by partial intravascular obstruction of the ascending aorta. Three weeks later, sildenafil was given (25mg/kg, oesophageal gavage once a day) for the next 2 weeks (group HFS, n=7). The group HFS was compared to the group of rats with left heart pressure overload for 3 weeks with no additional use of sildenafil (group HF, n=9) and with controls (group C, n=6). Mean pulmonary arterial pressure was significantly lower in the group HFS compared to the group HF (12.9±0.8 mmHg vs. 20.3±1.0 mmHg, p<0.0001, respectively) but was not different from the group C (10.7±1.1 mmHg). Weight of the right ventricle relative to the body weight (RV/BW ratio) as well as right ventricle weight relative to the left ventricle plus septum (RV/LV+S ratio) were significantly lower in the group HFS compared to the group HF (RV/BW ratio: 4.1±0.3.10−4 vs. 6.3±0.8.10−4; p<0.01, respectively and RV/LV+S ratio: 0.23±0.02 vs. 0.41 ±0.07; p<0.05, respectively) but they were not different in the group HFS compared to the group C in both parameters. The amount of expired nitric oxide, measured by chemiluminescent method on day 10 of the left heart pressure overload, was significantly increased in the group HF compared to the group C (343.0±30.5 pg/min/100g vs. 239.8±18.2 pg/min/100g; p<0.05, respectively). Sildenafil abolishes the developed pulmonary hypertension caused by the left heart pressure overload in the rats.Support or Funding InformationSupported by grants: GAUK 210216 and GACR 17‐11223SThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects on Breathing and the CO2 Chemoreflex of 5‐HT and NK‐1 Receptor Antagonists in the Retrotrapezoid Nucleus (RTN)
Authors: Dillard Matt L. , Mouradian Gary , Hodges Matthew R. 
Published: June 2021

Serotonin (5‐HT) and Substance P, typically increase the excitability of neurons within the neural network controlling breathing through G protein‐coupled receptors. These neuromodulators also stimulate pH/CO2 sensitive Phox2b‐expressing (Phox2b+) neurons in the retrotrapezoid nucleus (RTN), but their role in supporting the ventilatory CO2 chemoreflex within the RTN has not been tested in vivo. We hypothesize that unilateral antagonism in the RTN of 5‐HT and/or NK‐1 receptors will attenuate the ventilatory CO2 chemoreflex. To test this hypothesis, 8 week old male Sprague Dawley rats were chronically implanted with guide cannula unilaterally using stereotaxic coordinates previously published (Dias et al., 2008). After 7 or more days of recovery, microdialysis probes were inserted into the guide cannula for dialysis of mCSF alone followed by mCSF mixed with individual or a cocktail of antagonists to 5‐HT7 receptors (SB 269970 (100 μM)), 5‐HT2A receptors (MDL 11,939 (20 μM)) and/or NK‐1 receptors (SR 140333 (40 μM)) while measuring breathing in room air (35 min) and during a 7% CO2 challenge (10 min) before and during drug dialysis. We found that SB 269970 consistently reduced hypercapnic breathing frequency (−9 ± 2%, n=3) compared to mCSF alone, and had mixed effects on eupneic breathing and hypercapnic tidal volume. MDL‐11939 consistently reduced eupneic breathing frequency (−7 ± 0.4%, n=3) and hypercapnic tidal volume (−17 ± 0.8%, n=3) compared to mCSF alone, but had mixed effects on eupneic tidal volume and hypercapnic breathing frequency. In addition, a cocktail of all antagonists consistently increased eupneic breathing frequency (+14%, n=2) and decreased hypercapnic breathing frequency (−7 ± 0.4%, n=2) compared to mCSF alone. These preliminary data suggest 5‐HT and Substance P within the RTN may modulate breathing at rest and during hypercapnic conditions in vivo.Support or Funding InformationThis work was supported by NIH HL122358.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dropping the base: Characterizing the hypercarbia recovery strategies following extreme hypercapnia in the highly CO2 tolerant hagfish (Eptatretus stoutii)
Authors: Clifford Alexander Michael , Weinrauch Alyssa M. , Goss Greg G. 
Published: June 2021

As scavengers that feed on decaying carrion (e.g. fish, large marine mammals), hagfish (Eptatretus stoutii) can be subjected to noxious environmental stresses such as high ammonia, anoxia and hypercapnia. While the physiological impacts and the hagfishes' tolerance of these stressors have been well characterized, little data exists on the mechanisms and strategies for recovery from these stressors that would be mandatory in the natural environment. Indeed, hagfish are capable of tolerating extreme hypercapnia (>30 Torr; 72h) by building up plasma [HCO3−] over 24 – 48 h of exposure, attaining the highest plasma [HCO3−] levels ever observed in any organism (~70 mmol HCO3− L−1). The goal of this study was to characterize the hypercarbia recovery strategies of the highly CO2 tolerant following hypercapnia exposure. In a series of experiments, hagfish were exposed to hypercapnia (4% CO2) for 48 h to induce hypercarbia before being allowed to recover in normocapnic seawater. During this recovery period, measurements of blood acid/base status, plasma [Cl−] and net H+/HCO3− flux were made to elucidate the recovery strategies of the hagfish. Upon reintroduction into nonromantic conditions, hagfish rapidly (<8h) offloaded the compensatory base load (65.8 ± 2.1 mmol HCO3− L−1) while sustaining an incredible blood alkalosis of ~0.8 pH units compared to post‐exposure conditions, to a blood pH 8.67 ± 0.03 within 4h of recovery. While increases in both whole‐animal HCO3− excretion and glomerular filtration were observed throughout recovery (2–8 h), neither can fully account for the observed rates of whole‐animal HCO3− loss, which peaked at ~3.5 mmol kg−1 h−1. Inhibition of carbonic anhydrase using acetazolamide revealed that restoration of plasma [HCO3−] from hypercapnia‐induced hypercarbia is likely facilitated in a dualistic manner, initially relying on both carbonic anhydrase mediated CO2 offloading and Cl−/HCO3− exchange processes, both of which are likely either upregulated or further activated as recovery progresses.Support or Funding InformationNSERC (GGG: 203736)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Selective Depletion of Astrocytes Derived From a Phox2b‐Progenitor Domain Reduces Hypoxia Ventilatory Response in Conscious Mice
Authors: Silva Talita M. , Czeisler Catherine , Takakura Ana C. , Otero José J. , Moreira Thiago S. 
Published: June 2021

The peripheral chemoreceptors stimulate the respiratory pattern generator directly and indirectly by activating retrotrapezoid nucleus (RTN) via a neuronal projection from the nucleus of the solitary tract. The RTN neurons express the transcription factor Phox2b. In addition to neurons, astrocytes from ventral medullary surface appear to contribute to respiratory drive and have a developmental connection with RTN neurons, the aim of this study is determine the extent to which selective ablation of PHOX2B‐derived astrocytes affect ventilation during development. We interbred ALDH1L1loxp‐GFP‐STOP‐loxp‐DTA mice to PHOX2Bcre mice. Breathing variables [tidal volume (VT), respiratory frequency (fR), and minute ventilation (VE)] were measured by whole body unrestrained plethysmography in conscious adult mice. PHOX2B‐derived astrocytes ablation (genotype PHOX2Bcre, ALDH1L1loxp‐GFP‐STOP‐loxp‐DTA) reduces hypoxia (8% O2)‐induced increased in VE (3139.22 ± 250.76, vs. control [genotype ALDH1L1loxp‐GFP‐STOP‐loxp‐DTA] 4194.7 ± 235.16 μl/min/g; p = 0.021; n=6) and VT (13.93 ± 0.6, vs. control 16.53 ± 0.7 μl/g; p = 0.0019; n=6). Our results showed that ablation of PHOX2B‐derived astrocytes produced severely impaired O2 chemosensory response, indicating that these cells may be part of a specialized neural circuitry involved breathing activation.Support or Funding InformationFAPESP and NIHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Wall Shear Stress and Sphingosine‐1‐Phosphate Synergistically Activate Ca2+ Signaling via Piezo1 to Mediate Angiogenesis
Authors: Kang Hojin , Mittal Manish , Zhong Ming , Komarova Yulia , Mehta Dolly , Malik Asrar B. 
Published: June 2021

The sensing of wall shear stress (WSS) by endothelial cells (ECs) mediates sprouting angiogenesis; however, the underlying signaling mechanisms remain unclear. Here we investigated the synergism between WSS and the angiogenic mediator Sphingosine‐1‐phosphate (S1P) in activation of the mechanosensitive ion channel protein Piezo1, expressed in ECs. Studies were made in EC monolayers exposed to WSS of 5 dyne/cm2, the level approximating venular WSS, in which sprouting angiogenesis in 3D collagen matrix was assessed with and without challenge with S1P. WSS or S1P alone induced little angiogenesis; however, WSS combined with S1P resulted in robust angiogenesis suggesting that efficient angiogenesis requires both mechanical and humoral stimuli. These angiogenic responses were inhibited by suppression of Piezo1 expression in both human and murine endothelial monolayers as well as in vivo models. Specifically, studies in mice in which Piezo1 was conditionally deleted in ECs (Piezo1iEC‐KO) demonstrated the requisite role of S1P‐dependent activation of Piezo1 in mediating angiogenesis in vivo. S1P functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of calpain and the metalloproteinases, matrix metalloproteinase‐2 (MMP2) and membrane type 1‐matrix metalloproteinase (MT1‐MMP). S1P synergizes with WSS to induce Ca2+ influx via Piezo1 and thereby activate activities of MT1‐MMP, and mediate sprouting angiogenesis.Support or Funding InformationThis work is supported by T32 HL07829, AHA 17SDG33700146 grants to HK and HL45638 grant to YK and ABM.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex‐Specific Aspects in Cardiac Transplantation Evaluated by Left Ventricular Size in Male and Female Recipients
Authors: Kerkhof Peter L. , Parry Gareth 
Published: June 2021

BACKGROUNDBoth ejection fraction (EF) and end‐systolic volume (ESV) have been advanced as significant determinants of survival in patients with myocardial ischemia or heart failure. In heart transplant (HTX) patients sex‐based mismatch is recognized as an important factor for outcome. Also, it is well established that in the healthy adult population, as well as in various cardiac diseases, the left ventricular (LV) volume is significantly smaller in females (F) compared to males (M), even after indexation for body surface area.AIMOn the basis of the reported observations we investigated the impact of the various donor/recipient combinations on both ESV and EF, as well as on their interrelationship.METHODSIn previous studies we have demonstrated that EF is nonlinearly related to ESV, yielding identical regression curves for men and women based on the robust expression EF = 100 [1 + C1{ESV/(C2‐ESV)}], where C1 and C2 are population based constants. In 94 HTX patients we studied LV volume obtained by CT, where images were processed on a Siemens Syngo Via workstation.RESULTSDistribution of the various sex‐related combinations was: M to M (51), M to F (12), F to M (13), and F to F (18). We calculated ESV vs EDV regression lines to estimate C1 and C2.For M to M the C1 and C2 are 0.68 and −53.14, respectively, with R2=0.45For M to F the C1 and C2 are 0.83 and −64.86, respectively, with R2=0.84.Linearized EF versus ESV yields significant (P for all < 0.001) inverse relationships which for the four study groups are fairly similar. Despite the fact that 40% of the hearts were from male donors, ESV was found to be smaller (P=0.0019) in all female recipients, similar as observed in healthy women when compared to men. In contrast and against expectation, EF was not higher in female compared to male recipients, suggesting that an extra component beyond EF needs to be identified which may have better power to discriminate.CONCLUSIONSSex‐associated LV volumetric characteristics known from previous studies, also appear to be reflected in the recipients regardless of donor sex, suggesting that the LV size of the new heart tends to adapt to the sex of the recipient. We found that EF does not discriminate between the four groups, in contrast to ESV which is significantly smaller in female recipients, irrespective of the sex of the donor. Longitudinal studies may provide further clarification about the underlying mechanism(s) which are responsible for the sex‐specific adaptation in HTX recipients.Support or Funding Informationnone