bluuebunny/crossref_metadata_2025_split huggingface dataset:
Representing connectivity circuits in autonomic physiology: the SPARC map of organ innervation
Authors: Gillespie Tom , Martone Maryann 
Published: May 2023

The Stimulating Peripheral Activity to Relieve Conditions (SPARC) program is a NIH-funded consortium to improve the understanding of how the autonomic nervous system (ANS) interacts with end organs and the central nervous system. A major goal of SPARC is to use this knowledge to develop the next generation of neuromodulator devices as effective disease therapies. To support neuromodulation planning, the routes of ANS neuron populations (as well as those populations conveying visceral sensing) are to be mapped in terms of the anatomical structures where they pass through or terminate. Such a map would also serve as an organizing scaffold for (i) a growing SPARC repository of electrophysiology recordings and molecular assay data, as well as (ii) the computational simulation of the effect of neural stimulation on any relevant point on the CNS or ANS. The resulting SPARC map represents connectivity as a network of conduits, and is known as the SPARC Connectivity Knowledge Base of the Autonomic Nervous System (SCKAN). SCKAN contains explicit knowledge about CNS-ANS-end organ circuitry derived from SPARC data and scientific literature, in a form that supports computational reasoning. All connections are annotated with standard reference SPARC vocabularies allowing us to integrate datasets that are annotated to the same annotation standard. Circuits on the map represent details of ANS connectivity associated with a particular organ, e.g., bladder control, defensive breathing, modulation of peristalsis or cardiac inotropy/chronotropy. These circuits are created through interviews with SPARC investigators, anatomical experts and the scientific literature. They contain detailed representations of neuron populations giving rise to ANS connections, including mappings of the locations of cell bodies, dendrites, axon segments and synaptic endings. Circuits are modeled using ApiNATOMY, a knowledge model and tool suite specifically created to represent biological connectivity. Furthermore, these detailed circuits are supplemented with general knowledge on connectivity between CNS nuclei, ANS ganglia, nerves, and end organs derived from the scientific literature. To facilitate extracting this knowledge from the literature and maintaining relevance over time, we developed a Natural Language Processing (NLP) pipeline, which extracts connectivity relationships between unique anatomical structures within a sentence from the scientific literature. SCKAN is being used to create a queryable visual atlas of ANS circuitry through the SPARC portal. SPARC Funding: NIH Common Fund, NIH Office of the Director, Award OT2 OD030541 This is the full abstract presented at the American Physiology Summit 2023 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 interplay between iron regulation and ferroptosis cell death signaling
Authors: Garcia Jorge , Chapa Xavier , Javadov Sabzali 
Published: May 2023

Iron is an important ion that is mainly involved in different aspects of cellular metabolism. Normally, iron homeostasis is regulated by storage and transport proteins that help stabilize and facilitate transport throughout the body. Transferrin is the main iron transport protein in the blood; it transports ferric iron (Fe3+) from absorption sites to different tissue cells via endocytosis upon interacting with the transferrin receptor. In the cell, in addition to the cytoplasm, mitochondria are heavily involved in iron metabolism. The excess of labile (free unbound) iron in the cell can undergo the Fenton reaction to further enhance ROS production inevitably leading to cell death through apoptosis and/or ferroptosis. Ferroptosis is a new type of cell death that is mediated by iron-dependent lipid peroxidation and is associated with a myriad of diseases such as cardiovascular and neurodegenerative diseases, and cancer, among others. Mitochondria are involved in ferroptotic cell death signaling, nevertheless, the exact mechanisms underlying the contribution of mitochondria to ferroptotic signaling remain unknown. This study was performed to elucidate the effects of iron on cell viability and mitochondrial function in cardiomyocytes. H9c2 cardiomyocytes were cultured in the presence/absence of ferric ammonium citrate (FAC, 200 and 400 μM), tert-butyl hydroxide (TBH, 10 and 100 μM), and deferoxamine (DFO, 200 and 400 μM) individually and in combination. Cell death was quantified by the lactate dehydrogenase (LDH) activity in the culture media whereas mitochondrial function was estimated by changes in the mitochondrial membrane potential measured by using TMRM, a potential-sensitive fluorescent dye. Our results show that TBH at low concentrations or FAC at both low and high concentrations did not induce cell death. However, FAC at high concentration (400 μM) in combination with TBH (10 μM) significantly increased cell death. Additionally, DFO alone induced cell death, demonstrating the importance of maintaining iron balance in cellular media. In conclusion, this study demonstrated that the detrimental effects of iron (FAC) on cell viability are increased in the presence of oxidative stress (TBH) in H9c2 cardiomyocytes. This study was supported by the National Institutes of Health (Grant R16GM145390). This is the full abstract presented at the American Physiology Summit 2023 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.
Reactive hyperemia acutely decreases peripheral arterial stiffness
Authors: Jackson Ronald , Lima Natalia , Sherman Sara , Clifford Philip 
Published: May 2023

Previous studies have shown that peripheral arterial stiffness can be reduced acutely by exercise, mechanical compression, and heat. Since reactive hyperemia elicits large increases in conduit artery blood flow similar to the other maneuvers, it may have similar effects on peripheral arterial stiffness. However, the effect of reactive hyperemia on peripheral arterial stiffness has not been investigated. We tested the hypothesis that reactive hyperemia would acutely decrease peripheral arterial stiffness as measured by pulse wave velocity (PWV). Seven healthy young adults (4 women; age: 30 ±4 years; mean±SD) were included in this study. Brachial to radial PWV was measured by placing pulse tonometer’s simultaneously over the brachial and radial arteries. Reactive hyperemia was performed using a rapid-release cuff positioned on the right upper arm, inflated to 220 mmHg and sustained for 5 min. Arterial blood pressure was continuously monitored via photoplethysmography beat by beat on the middle finger of the contralateral hand. Measurements were made before cuff inflation and at 5, 15, and 30 min after cuff release. At baseline before cuff inflation, brachial to radial PWV was 10.8 ±1.6 m/sec. PWV decreased (p<0.05) to 8.7 ± 1.8 m/sec at 5 min. PWV was not different from baseline (p>0.05) at 15 min (10.8 ± 2.7 m/sec) or at 30 min (10.1 ± 3.3 m/sec). Mean arterial pressure (MAP) was not significantly different (p>0.05) across time points. The results show that reactive hyperemia produces an acute reduction in brachial to radial PWV. However, the reduction was not long lasting. This was a local response not confounded by arterial pressure changes. The large increase in conduit artery blood flow or trapped metabolites may provide a potential mechanism. This is the full abstract presented at the American Physiology Summit 2023 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.
Developmental changes in cardiac composition before and after birth in sheep
Authors: Vasquez Reyes Kaylee-Abril , Louey Samantha , Jonker Sonnet 
Published: May 2023

Introduction: The myocardium is made up of many elements that each play an important role in heart function. The contractile cardiomyocytes proliferate prenatally, and become terminally differentiated in the weeks leading up to birth. Despite a loss of ~ 1/3 of the cardiomyocytes about 1 week before birth, the hearts continue to increase in size (Jonker et al., 2015). At birth, the demands on the cardiovascular system change, which may affect the relative cellular makeup of the myocardium. In this study, we determined the fractional composition of the myocardium in four different ages around the time of birth. Methods: Hearts, arrested in diastole, were collected from control fetal (135d and 142d gestational age; dGA; term is 147d) and newborn (1d and 5d postnatal age; PN) lambs. Sections of left ventricle were fixed (4% paraformaldehyde), paraffin embedded and stained (Masson’s Trichrome). Images (400x) were analyzed by unbiased sampling (grid system, FIJI) to classify according to these categories: cardiomyocyte cell body, cardiomyocyte nucleus, blood vessel lumen, blood vessel wall, collagen, non-collagen connective tissue. All values are represented as percent of total area (±SD). Groups (n=3-4 each age) were compared by 1-way ANOVA followed, if indicated, by Tukey's multiple comparisons test. Males and females were both represented in each age (135dGA, 143dGA, 1dPN, 5dPN: n=1/2, 2/2, 3/1, 2/1, respectively). Results: The average area composed of cardiomyocyte for all groups was 81.7 ± 7.4%, and did not differ between ages. The average area composed of vasculature for all groups was 8.6 ± 5.2%, and did not change with age. Connective tissue area was 3-fold greater at 1dPN (8.5 ± 3.6%) than 143dGA (2.8 ± 1.2%, P<0.05) and 5dPN (2.5 ± 0.8%, P<0.05). This was not due to more collagen, which did not differ between ages. Further analysis of the cardiomyocyte fraction indicated that the nucleus was 60% larger (compared to total myocyte area) at 1dPN (P<0.04; in advancing age order: 18.2 ± 3.3%, 14.2 ± 1.0%, 26.3 ± 4.9%, 17.1 ± 1.8%). Conclusion: Our preliminary analysis indicates little change in the cellular composition of the left ventricle myocardium, save for a transient increase in connective tissue area and larger nuclei per cardiomyocyte area 1 day after birth. A change in glycogen after birth could be a factor that leads to increased cardiomyocyte nuclear area per cytoplasm and increased relative fraction of connective tissue. This study was funded by NIH NHLBI R01HL142483. KAVR was funded by a NIH supplement to R01HL142483. This is the full abstract presented at the American Physiology Summit 2023 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 response of fetal sheep cardiomyocytes to intralipid infusion
Authors: Iverson Kaliyah , Loey Samantha , Jonker Sonnet 
Published: May 2023

Introduction: The developing heart undergoes changes in metabolic substrates parallel with perinatal developmental stages. The preferred substrates for fetal hearts are carbohydrates, which transitions to a preference for fatty acids postnatally. The underdevelopment of lipid metabolism mechanisms in preterm infants cause imbalances or dysfunction in uptake, cellular processing, and storage of fatty acids; and increase the risks for long term cardiovascular and metabolic diseases. It is unknown whether the heart can process fatty acids before birth, and how it affects cardiomyocyte growth. The aim of this study was to determine the effects of Intralipid infusion on fetal sheep cardiac myocyte growth. We hypothesized that the size of cardiomyocytes would remain unchanged, however we expected an increase in maturity. Methods: Intralipid 20® was infused into instrumented fetal sheep (IL, 0.4 ml/kg/hr for 8 days, n=4F/7M); the contralateral twin received saline at a comparable rate (CON, n=7F/4M). Hearts were collected at 133 days gestational age (dGA; term is 147 dGA), and enzymatically dissociated, then myocytes fixed in paraformaldehyde. The length and width were measured in 100 myocytes using a wet mount, under calibrated light microscopy (40x, Zeiss Axiophot), and analyzed with Image Pro 6.3. Nucleation was determined in 500 cells; percentage binucleation is a surrogate measure of maturation. Data are presented as mean ± standard deviation. Groups were compared by t-test. Results: Body weight (IL, 4.2 ± 0.6 vs. CON, 4.1 ± 0.6kg) and heart weight (IL, 29.9 ± 4.1 vs. CON, 27.2 ± 4.6g) were not different between the lipid and control fetuses. Interim results indicate no differences in length or diameter in cardiomyocytes of the left and right ventricle (IL, N=3-7; CON, N=7-9). We found no differences in cardiomyocyte length in the septum, but Intralipid (N=10) increased the diameter of mononucleated (+12%, P=0.016) and binucleated (+11%, P=0.012) myocytes (vs. CON, N=7). In the septum, Intralipid treatment increased binucleation (P<0.02; 69.2 ± 8.0% vs 60.8 ± 9.7%). In the RV, increased binucleation was only a tendency (P<0.06; 70.7 ± 6.4% vs 60.8 ± 9.9%; IL n=6). Binucleation was unaffected in the LV (67.1 ± 9.9%). Summary/Conclusion: The increase in diameter of fetal cardiomyocytes in the septum could reflect different regional regulation of growth to the infused intralipid. Interestingly, parallels could be made between the septal hypertrophy described in offspring from diabetic mothers. This study is funded by NIH R01HL146997 and R01HL142483. KI is funded by a NIH supplement to R01HL142483. This is the full abstract presented at the American Physiology Summit 2023 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.
Influence of Hydration Status and Plasma Copeptin on Ambulatory Blood Pressure in Healthy Young Adults
Authors: Jeong Soolim , Barnett Alex , Linder Braxton , Tharpe McKenna , Hutchison Zach , Culver Meral , Nichols Olivia , Fuller-Rowell Thomas , Watso Joseph , Robinson Austin 
Published: May 2023

BACKGROUND: Adequate hydration is essential for regulating various physiological systems and may influence blood pressure (BP). Hypohydration is linked with elevated copeptin (surrogate of arginine vasopressin), which is associated with elevated cardiovascular disease risk. However, there is limited information on the influence of hydration and copeptin on ambulatory BP measures in young adults. Therefore, we sought to investigate associations between hydration, copeptin, and ambulatory BP. METHODS: We studied 41 participants (19 M/22 F, 24 White/17 Black, age 21±1 years, body mass index 26±5 kg/m2, screening BP 111± 10/67±8 mmHg; Mean ± SD) who provided a 24-hour urine sample. We measured urine specific gravity (USG), urine osmolality (OSM), and plasma copeptin as biomarkers of hydration. We used ambulatory BP monitoring (Suntech Oscar2) to assess BP during daytime (1000-2000) and nighttime (0000-0600). Our primary outcomes were plasma copeptin (pmol/L) and night-to-day BP dip ratio (nighttime/daytime BP) in dehydrated (USG >1.020 or OSM >800 mOsm/kg) vs euhydrated participants. Statistical procedures included Student’s t-tests and Mann-Whitney U tests. We also used Spearman’s rho correlation (controlling for BMI, sex, and race). We set α at ≤0.05. RESULTS: Copeptin concentration was elevated in dehydrated compared with euhydrated participants (USG: 6.6±2.9 vs 4.3±2.0 pmol/L, p<0.005; OSM: 6.6±2.7 vs 4.1±2.0 pmol/L, p<0.001). After controlling for BMI, sex, and race, copeptin was associated with USG (rho=0.44, p=0.005) and OSM (rho=0.51, p=0.001). Systolic and diastolic BP dip ratios did not differ by hydration status for either USG or OSM ( ps>0.179). Additionally, adjusted BP dip ratios were not correlated with OSM or USG ( ps>0.149). Plasma copeptin was not associated with BP dip ratios ( ps>0.155) but was associated with absolute nocturnal systolic (rho=-0.34, p=0.036) and diastolic BP dip (rho=-0.33, p=0.041). When we split participants by low and high copeptin concentration (median split), higher copeptin was associated with a lower (i.e., worse) systolic BP dip ratio (0.87±0.06 vs 0.90±0.06, p=0.048) and lower absolute nocturnal systolic and diastolic BP dip ( ps<0.01). CONCLUSIONS: Hydration biomarkers were correlated with plasma copeptin, but not ambulatory BP. The significance of our findings are that higher copeptin was associated with blunted nocturnal BP dipping in younger adults, which could predispose them to increased future cardiovascular disease risk. This is the full abstract presented at the American Physiology Summit 2023 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.
Dysregulation of hepatic microcirculatory function and tissue oxygenation in a rodent model of sleep apnea
Authors: Marcus Noah , Gadkari Priyanka , Smith Carter , Highum Aubrey , Gerritts Raina , Madigan Benjamin , Harbeck Katherine , Lei Ryan , Schwartz Kelsey , Lang James , Clayton Sarah 
Published: May 2023

Sleep apnea (SA) is highly prevalent in patients with non-alcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD is incompletely understood however hemodynamic dysregulation and tissue hypoxia are hypothesized to play important roles. SA is associated with vascular and autonomic dysfunction however its effects on hepatic hemodynamic control have not been explored. We hypothesized that exposure to an experimental model of SA (CIH) would result in exaggerated reductions in hepatic perfusion (HP) and tissue PO2 (HPO2) during intermittent asphyxia (IA) and that these changes would be exacerbated by ovariectomy (OVX). Female Sprague Dawley rats (n=4-6 per group) were exposed to CIH or sham for 8h/d for 14 days. At the conclusion of CIH or sham, HP and HPO2 responses to IA (ten episodes FiO2 10%, FiCO2 3%, 30s each) were measured under anesthesia. Data was analyzed using ANOVA or unpaired t-tests. IA normoxic HP and PO2 was significantly decreased relative to pre-AIH in all groups, but HP was markedly lower in OVX-CIH vs sham or CIH (p<0.05). Reduction in HP during the hypoxic portion of IA was greater in CIH and OVX-CIH than sham (p<0.05) but was not different between the two CIH groups. HPO2 decreased to a greater extent in CIH v. sham during the hypoxic portion of IA (p<0.05). In conclusion, 14 days of CIH causes dysregulation of hepatic hemodynamics and tissue PO2 and loss of female sex steroid hormones may exacerbate these changes. Our findings identify a potential role of SA in the pathophysiology of NAFLD. DMU Mentored Student Research Program This is the full abstract presented at the American Physiology Summit 2023 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.
Spontaneous Cardiac Baroreflex Sensitivity in Young, Healthy Black and White Adults: Influence of Race and Sex
Authors: Taherzadeh Ziba , Garza Nicole , Skow Rachel , Young Benjamin , Nandadeva Damsara , Stephens Brandi , Grotle Ann-Katrin , Fadel Paul 
Published: May 2023

Background: Black (BL) individuals living in the United States are more likely to develop hypertension and cardiovascular disease compared to their White (WH) counterparts. However, studies investigating racial differences in blood pressure regulation and baroreflex sensitivity (BRS) are limited and have reported equivocal results. Furthermore, despite BL females also having a high prevalence of hypertension and cardiovascular disease, sex differences are often not considered. Additionally, baroreflex effectiveness index (BEI) is a newer measure used to estimate baroreflex function, yet studies have not examined the influence of sex or race on BEI. Therefore, the purpose of this project was to investigate the effects of both race and sex on cardiac BRS and BEI. We hypothesized that BL individuals would have lower cardiac BRS and BEI than WH individuals. Methods: We studied 88 young healthy adults, 28 BL males (21 ± 3 years; mean ± SD), 17 WH males (24 ± 4 years), 15 BL females (21 ± 3 years), and 28 WH females (23 ± 4 years). Heart rate (ECG) and beat-to-beat arterial blood pressure (finger photoplethysmography) were continuously recorded during a five-minute resting baseline. Cardiac BRS was measured using the Sequence Method, by identifying the gain of the relationship between systolic blood pressure and RRI from sequence(s) of three or more consecutive heartbeats in which systolic blood pressure and RRI change in the same direction. BEI was quantified by baroreflex-driven ramps relative to all systolic blood pressure ramps. Results: Cardiac BRS was significantly higher in BL individuals (31 ± 15 ms/mmHg) compared to WH individuals (25 ± 11 ms/mmHg; main effect of race, p = 0.02). Interestingly, post hoc comparisons revealed that this was only true within the males (p = 0.03), but not females (p = 0.63). However, there was no difference in cardiac BRS between males and females (main effect of sex, p = 0.35) and no interaction between sex and race (p = 0.27). There were also no effects of race (p = 0.65) or sex (p = 0.15) on BEI. Conclusion: These preliminary data suggest that, in contrast to our hypothesis, young BL individuals have higher cardiac BRS compared to WH individuals; an effect that is only present in males. In contrast, BEI was not influenced by race or sex. Collectively, our findings do not suggest that lower cardiac BRS plays a major role in the higher prevalence of cardiovascular disease in BL individuals. This is the full abstract presented at the American Physiology Summit 2023 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.