bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Modulation of Leg Shear Rate Profile in Young and Older Adults
Authors: Hanson Brady , Fermoyle Caitlin , Alpenglow Jeremy , LaSalle Taylor , Craig Jesse , Bunsawat Kanokwan , Broxterman Ryan 
Published: May 2024

Aging alters the shear rate profile in the arm, characterized by increased oscillatory (bidirectional) shear, potentially from progressive increases in sympathetic nervous system activity. However, the extent to which the shear profile in the atheroprone vasculature of the leg is mediated by sympathetic overactivity via α-adrenergic receptor activation is unknown. We sought to determine how pharmacological modulation of α-adrenergic receptor activity alters shear in the femoral artery with aging. We hypothesized, within the leg, that increased α-adrenergic vasoconstriction would lead to a pro-atherosclerotic shear profile in young adults while α-adrenergic blockade would improve the shear rate profile in older adults, as previously reported in the arm. Resting femoral artery shear rate profiles were assessed in five young (4M/1F, 26±5 yr) and seven older (4M/3F, 65±7 yr) adults during saline (control), phentolamine (PHEN, nonselective α -adrenergic antagonist), and phenylephrine (PE, a selective α-adrenergic agonist) intra-arterial infusions using Doppler ultrasound. Under control conditions, there were no age-related differences in antegrade, retrograde, or total (antegrade + retrograde) shear rates. During PHEN infusion, antegrade shear increased in both young and older adults (Y: 597±214 v. 1011±313 s−1; O: 412±168 v. 648±334 s−1, p<0.05 for both), while retrograde (Y: 122±49 v. 62±21 s−1; O: 109±59 v. 54±43 s−1, p<0.05 for both), and oscillatory shear decreased (Y: 0.17±0.01 v. 0.06±0.01; O: 0.20±0.02 v. 0.09±0.02, p<0.05 for both) compared to control. Although the magnitude of change was similar between age groups, antegrade and total shear were greater in young following PHEN. Infusion of PE had no effect on antegrade (Y: p=0.16; Op=0.78,), retrograde (Y: p=0.83; O: p=0.17), and oscillatory shear (Y: p=0.25; O: p=0.09) but did cause an age-related separation in antegrade and total shear such that the young were greater following PE. Collectively, these preliminary data suggest withdrawal of α-adrenergic vasoconstriction with PHEN leads to a more favorable shear pattern (i.e., increased antegrade shear, and decreased retrograde and oscillatory) within the femoral artery, independent of age. Overall, these findings indicate that femoral shear rate may be influenced by the α-adrenergic system in a manner that is uniquely different from what has been previously reported in the arm. R01HL142603, I01CX001999, IK2RX001215. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Science Communication Training for Graduate Exercise Physiology Students
Authors: Elmer Steven 
Published: May 2024

Physiologists have a responsibility to inform the public about how new discoveries and challenges will impact the health of society. However, most physiologists do not have formal training in science communication. The purpose of this study was to implement a science communication training pilot program for graduate students. Students (n = 23) were introduced to science communication training that emphasized key skill development (writing, public speaking, leadership, project management, teaching) as part of their advanced exercise physiology course. Subsequently, students carried out service-learning projects that tasked them with presenting evidence-based health information to public audiences (e.g., community members, clinicians, K-12 students, journalists, policy makers). In a subset of students (n = 8), a survey was administered to assess students’ perceptions of the value of science communication and their ability to communicate to different audiences. Service-learning projects that students completed included blog posts, infographics, podcast series, visits with K-12 schools, and public townhall presentations. Most students (≥75%) agreed that completing the science communication training helped them develop confidence speaking to a range of audiences. After completing the science communication training, students were more interested in learning about how to better communicate science concepts to the public compared to before the training (88% vs. 25%). Collectively, these preliminary results suggest that science communication training helped graduate exercise physiology students recognize the gap between science and society, develop confidence speaking to a range of audiences, and communicate more effectively. These results support findings from other disciplines such as biology and medicine. Implementation of science communication training is paramount, and the approach described here could be useful for physiology students, educators, and departments. American Physiological Society - Teaching Career Enhancement Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Proteomics Approach to Identify Anthracycline-induced Cardiotoxicity Mechanisms in Human Cardiac Fibroblasts
Authors: Bagchi Ashim , Holdiness Ryan , Dhar Anya , Stolarz Amanda , Bagchi Rushita 
Published: May 2024

Doxorubicin-induced cardiotoxicity (DIC) is a major life-threatening side-effect of chemotherapy in cancer patients. DIC leading to heart failure is caused by numerous mechanisms, including impaired mitochondrial function, disruption of calcium homeostasis, and altered gene and protein response that triggers cell death and, eventually, fibrosis. We performed a preliminary investigation of the effect of doxorubicin (DOX) on the cardiac fibroblast proteome using mass-spectrometry. Quantitative analysis showed significantly altered expression of 186 proteins. Nine out of forty-two Dox-upregulated proteins and seventeen out of twenty-four Dox-downregulated proteins showed a reciprocal trend in expression upon inhibiting a structural scaffold protein involved in cardiac calcium channel regulation. Overall, our data suggests the involvement of pathways in regulating mitochondrial energy metabolism, matrix remodeling, cell cycle/arrest, and cell survival via Rho/Rac nuclear exchanger proteins. DIC is multifactorial, and based on our pilot data, modulation of calcium channel regulators may be a promising strategy to mitigate the progression of DIC to heart failure. Research support received from the American Heart Association, NIH and the University of Arkansas for Medical Sciences. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Empagliflozin Extends Lifespan While Reducing Physical Activity in Drosophila Melanogaster: Insights into Non-Glycemic Pharmacological Effects
Authors: Brim-Edwards Jackson , Harris Hailey , Vrailas-Mortimer Alysia , Robinson Matthew , Newsom Sean 
Published: May 2024

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin (EMPA), are primarily used to manage hyperglycemia in type 2 diabetes (T2D). Beyond their role in glycemic control, SGLT2i can elicit off-target effects, including induction of a mild energetic stress phenotype—a state previously associated with increased longevity in various organisms. Drosophila melanogaster lack the SGLT2 protein and, therefore, can be used to model the effects of SGLT2i independent of renal glucose reuptake. We tested the hypothesis that EMPA would promote and increase longevity and physical activity (PA) by providing adult virgin female Drosophila with either DMSO (vehicle) or EMPA in the diet at concentrations of 5 μM, 25 μM, and 50 μM. EMPA treatment resulted in a significant extension of median lifespan at all concentrations: 4% (p=0.049) for 5 μM, 24% (p=0.035) for 25 μM, and 8% (p=0.025) for 50 μM, compared with DMSO. A linear mixed model analysis also demonstrated significant interactions between EMPA treatment and time on PA levels—5 μM (p=0.001), 25 μM (p=0.04), and 50 μM (p=5.85e-07)—indicating a pronounced reduction in PA over time in EMPA-treated groups compared with DMSO. Our findings that EMPA promotes longevity and lowers physical activity in Drosophila demonstrate that SGLT2i can have significant physiologic impacts that are independent of inhibition of SGLT2. Supported by funding from the Valley Fellowship (Oregon State University) awarded to SAN. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Cardiorenal Effects of Chronic High Phosphate Diet in Female Rats
Authors: Williams Adaysha , Yunker Lauren , Kriegel Alison 
Published: May 2024

Cardiorenal Syndrome Type 4 (CRS4) refers to the development of cardiovascular dysfunction as a result of chronic kidney disease. The accumulation of circulating phosphate in the later stages of chronic kidney disease (CKD) has been positively associated with cardiac hypertrophy and dysfunction. In our previous work, we found that male Sprague Dawley rats that underwent 5/6 nephrectomy (5/6Nx) to induce CKD phenotypes also developed cardiac pathology when serum phosphorus levels became elevated. Small RNA sequencing of left ventricle tissue revealed upregulated microRNA-21-5p and -3p expression in 5/6Nx rats, when compared to sham-operated controls, and suppression of miR-21-5p attenuated left ventricle pathology in male 5/6Nx rats. We hypothesize that hyperphosphatemia, independent of CKD, can impair cardiac function and that miR-21 may mediate these effects. It has been recently reported that females exhibit higher urinary phosphate excretion in response to high dietary phosphate intake than males. In this study, hyperphosphatemia was induced by placing 9-week old female wild-type (WT) Sprague Dawley and global miR-21 knockout (miR-21−/−; lacking both miR-21-5p and -3p rats) (n=4-9/group) on either high phosphate (2% Pi) or control diet (0.6% Pi) for 8 weeks. Echocardiography and renal ultrasound were performed under anesthesia to assess cardiac function and renal cross-sectional area, respectively, prior to tissue collection at endpoint. Rats of either genotype fed 2% Pi diet exhibited increased left kidney weight, left kidney/body weight, and left kidney cross-sectional area (2-way ANOVA, main effect of diet; p<0.05). In animals fed 2% Pi, miR-21−/− rats had significantly higher left ventricle fractional shortening than WT rats (57.06 ± 3.32 vs. 43.96 ± 1.34; 2-way ANOVA with Tukey multiple comparisons; p<0.05). This study allowed the cardiovascular effects of chronically elevated phosphate to be isolated from other uremic toxins elevated in CKD. We find that loss of miR-21 augments cardiac function, supporting a role for miR-21 in mediating phosphate-related pathology. Ongoing studies are focused on identifying specific molecular mechanisms driving these changes. This study was supported by T32HL007852 and R01HL128332. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Rapsyn overexpression improves recovery of the neuromuscular junction from tourniquet-induced ischemia-reperfusion injury in mouse hindlimb
Authors: Tu Hui Yin , Barksdale Aaron N , Wadman Michael C , Li Yu-Long 
Published: May 2024

The neuromuscular junction (NMJ) is an important factor to influence skeletal muscle contractile function. Tourniquet-induced ischemia-reperfusion (IR) results in the fragmentation of nicotinic acetylcholine receptors (nAChR) clusters in the NMJ and impairs neural controlled skeletal muscle contraction. Rapsyn, a cytoplasmic nAChR-associated protein concentrates and anchors nAChRs in the postsynaptic membrane and participates in the nAChR assembly at NMJ. Here, we observed the effect of overexpression of Rapsyn on morphological and functional recovery of the NMJ from tourniquet-induced IR injuries in mouse hindlimb. Unilateral hindlimb of C57/BL6 mice were subjected to 3 hours of ischemia by placing a rubber band and followed 6 weeks of reperfusion. Ad-m-RAPSN (5.2 x 1010 PFU/ml) was injected into gastrocnemius muscle (50 μl) by Hamilton microliter syringe after 2 weeks of tourniquet-induced IR. After 6 weeks of IR, the sciatic nerve-stimulated gastrocnemius muscle contraction and endplate potential (EPP) were recorded in in-situ muscle samples; the NMJs were labelled with alpha-bungarotoxin (BTX) and nerofilment-200 (NF-200) + synaptophysin (Syn) antibodies, and NMJ images were captured with Zeiss LSM 800. After 6 weeks of IR, NMJs in the gastrocnemius muscle showed significantly fragmented nAChR clusters (9.3 ± 0.7 vs. sham 1.7 ± 0.1 for numbers of fragments) with low rapsyn expression, and the EPP (15.29 ± 0.93 mV vs. sham 26.87 ± 0.89 mV) and nerve-stimulated muscle contraction (117.2 ± 8.5 g vs. sham 157.9 ± 4.9 g) were reduced. Ad-m-RAPSN injection increased rapsyn expression, mitigated fragmentation of nAChR clusters (3.2 ± 0.3), increased the EPP (20.35 ± 0.86) and nerve-stimulated muscle contraction (138.1 ± 3.5 g). The data suggest that tourniquet-related IR induces AChR cluster fragmentation and impairs NMJ function, and rapsyn overexpression improves the morphological and functional recovery of the NMJ from tourniquet-induced IR injuries.. This research is supported by the NIH/NIGMS 1R01GM145736 to Y-LL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Addressing the enigma of treating heart failure with preserved ejection fraction with P2X3 receptor antagonism
Authors: Pachen Mridula , Chen Robert , Chang Joshua , F.R Paton Julian , Ramchandra Rohit 
Published: May 2024

Heart failure with preserved ejection fraction (HFpEF) is a major health burden and a primary cause of death globally, yet there remains no curative treatment. Previous studies have indicated an important role for P2X3 receptors (P2X3R) in mediating high levels of sympathetic drive in hypertension (1). Given the high sympathetic drive in HFpEF(2), we investigated whether P2X3R antagonism would improve this condition. We tested the hypotheses that in HFpEF, P2X3R activation causes high levels of blood pressure and excessive vasoconstriction in the hindlimb vasculature during exercise. Following unilateral renal artery clipping, an ovine model of HFpEF was established in female sheep displaying hypertension and diastolic dysfunction. A sham-operated group acted as a control. Mean arterial pressure (MAP), heart rate (HR), and hindlimb blood flow (HLBF) were recorded before and during treadmill exercise, and the effect of either a P2X3R antagonist (L227, 10mg/kg) or vehicle was assessed. The clipping of one renal artery increased MAP (91±5 vs. 131±6, p≤0.05). The administration of the P2X3R antagonist reduced both MAP (-6±7 mmHg, p≤0.05) and HR (-6±6 bpm, p<0.05) in HFpEF sheep but no effect in sham-operated animals. HLBF during exercise was attenuated in the HFpEF model compared to sham-operated sheep (an increase of 2±1 vs. 4±2 L/min, respectively, p<0.05). Importantly, P2X3R blockade improved the change in HLBF during exercise from 1±0.1 to 2±0.4 L/min in HFpEF sheep, but there was no change in the sham-operated animals. There was no change in the MAP or HR response to the exercise with the P2X3R blockade. P2X3R plays a role in the aetiology of hypertension and in the attenuation of HLBF responses during exercise in HFpEF. P2X3R antagonism may provide a novel target to alleviate symptoms of HFpEF and improve exercise tolerance through increased HLBF. 1. Pijacka W, Moraes DJ, Ratcliffe LE, Nightingale AK, Hart EC, da Silva MP, Machado BH, McBryde FD, Abdala AP, Ford AP and Paton JFR. Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nature medicine 22: 1151-1159, 2016. 2. Seravalle G, Quarti-Trevano F, Dell’Oro R, Gronda E, Spaziani D, Facchetti R, Cuspidi C, Mancia G, and Grassi G. Sympathetic and baroreflex alterations in congestive heart failure with preserved, midrange and reduced ejection fraction. Journal of Hypertension 37: 443-448, 2019. Health Research Council of New Zealand and Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Designing and testing an Integrated Study Strategy: Core Concepts in physiology and Mind Maps
Authors: Gomez-Camacho Sarahi , Galván Zorrilla Dana Camila , García-Muñoz Katya Michelle , Sánchez-Briones María Eugenia 
Published: May 2024

This abstract shows the result of an innovative approach for learning physiology by combining two widely recognized methods: Core Concepts in physiology and Mind Maps. The objective is demonstrating the graphic product that visualize conceptual relationships holistically (mind map) combined with core concepts in cardiovascular physiology generated by a group of students enrolled to the integrative physiology course (2nd-year medical students, medical bachelor's degree, Professional Studies Faculty, Autonomous University of San Luis Potosí, México) during the semester august to December 2023. Methods: the curriculum content of cardiovascular physiology includes excitation-contraction coupling of the heart, the heart cycle, determinants of arterial pressure and peripheric vascular characteristics, including special circulations. The development of the mind map was according to the academic content of the course (4 weeks). The group of students worked with a training physiology teacher (including core concept training) for one 2-hour session per week (total= 4 sessions). The result is a mind map that includes the aspects of cardiovascular physiology addressed by the core concepts tool. Conclusion: Contemporary education faces increasing challenges in information retention and comprehension., and in this context, the integration of these two strategies emerges as a promising solution. This combination of learning tool is applicable in environments of low socioeconomical status because not involve doesn´t involve any monetary investments. Curricular Commission and the Academy or Clinical and Basic Sciences belonging to the bachelor´s degree of the Professional Studies Faculty, Autonomous University of San Luis Potosí, México. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The effcacy of short-term tetrahydrobiopterin administration to improve locomotor muscle microvascular function in heart failure with preserved ejection fraction
Authors: Bunsawat Kanokwan , Jarrett Catherine , Broxterman Ryan , Craig Jesse , Francisco Michael , Alpenglow Jeremy , Iacovelli Jarred 
Published: May 2024

Background: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit locomotor muscle microvascular dysfunction due partly to reduced nitric oxide (NO) bioavailability. Tetrahydrobiopterin (BH4) is a requisite cofactor for the enzymatic production of NO by NO synthase (NOS). BH4 insuffciency promotes NOS uncoupling, which reduces NO production and augments cellular oxidative stress. Given the potential of BH4 to improve NO bioavailability, we tested the hypothesis that short-term BH4 administration would improve locomotor muscle microvascular function in patients with HFpEF. Methods: Eight patients with HFpEF (74±7 years; 31.3±4.9 kg/m2) participated in a randomized, double-blind, crossover study, having consumed either BH4 (Sapropterin, 10 mg/kg) or placebo for 10 days, separated by a 14-day washout period. Locomotor muscle microvascular function was assessed as leg blood flow (LBF) and leg vascular conductance (LVC) responses to passive leg movement (PLM) before (pre) and after (post) each treatment. PLM-induced LBF and LVC responses were expressed as peak change (Δpeak) or total hyperemic response (area under the curve above baseline; AUC). Results: LBFΔpeak did not change following BH4 (267 ± 136 mL/min vs. 250 ± 101 mL/min) or placebo (317 ± 119 mL/min vs. 269 ± 97 mL/min) administration (pre vs. post; p>0.05). Similarly, LVCΔpeak was unchanged following either BH4 (396 ± 165 mL/min/100mmHg vs. 465 ± 180 mL/min/100mmHg) or placebo (579 ± 238 mL/min/100mmHg vs. 496 ± 185 mL/min/100mmHg) administration (pre vs. post; p>0.05). The changes in LBFAUC and LVCAUC were not affected by either treatment (LBFAUC; BH4: Δ91 ± 103 mL vs. Δ82 ± 69 mL; placebo: Δ148 ± 119 mL vs. Δ87 ± 81 mL; LVCAUC; BH4: Δ65 ± 55 mL/100mmHg vs. Δ98 ± 78 mL/100mnHg; placebo: Δ182 ± 127 mL/100mmHg vs. Δ105 ± 94 mL/100mmHg) (pre vs. post; p>0.05). Conclusion: Short-term BH4 administration did not improve locomotor muscle microvascular function in patients with HFpEF. This project was funded, in part, by the National Institutes of Health (HL118313, D.W.W.; T32HL139451, K.B.; the U.S. Department of Veterans Affairs (I01RX001311, D.W.W.; IK2RX003670, to K.B.), and the American Heart Association (18POST33960192; K.B.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.