bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compliance and Elasticity in Medical Physiology: Confusion and Clarification
Authors: Laban Nora , Dawood Radwa , Kuang Serena 
Published: May 2023

The concepts of compliance and elasticity are both used in medical physiology to describe how a soft tissue reacts to an external force. In general, compliance is defined as ΔV/ΔP (a change in volume (V)/a change in pressure(P)), but the interpretations of this definition are inconsistent. When compliance is addressed, the definition of elasticity is not presented, so the relationship between compliance and elasticity is not addressed, which causes confusion in students’ learning of the two concepts. The goals of this study are 1) draw attention to the inconsistent definitions through an analysis of teaching materials; 2) eliminate the confusion by supplementing the missing information to provide a complete picture of the two related concepts; and 3) illustrate how these concepts should be applied to 1-D and 3-D deformation in soft tissues. Results are as follows. 1) Inconsistent interpretations of compliance: Among 16 medical physiology textbooks and 2 USMLE Step 1 review books analyzed regarding the heart, arteries and vein, 33% of books claim compliance related to elasticity (without showing how), 22% to stiffness, 44% to distensibility, and 17% to capacitance. 2) The missing content but essential to medical physiology: In material science, Young’s/elastic modulus (E) and Bulk’s modulus (K) measure the elasticity for 1-D and 3-D materials respectively. Their relationship with compliance are formally addressed and mathematically illustrated via the following equations: E= σ/ε, where E is elastic modulus, σ is stress, and ε is strain; and K= - ΔP/(ΔV/V0), where K is Bulk’s modulus, and V0 is initial volume, and ΔP/(ΔV/V0) is compression. 3) During a vessel’s constriction, a point in the vessel’s wall moves in a 1-D dimension, so in dealing with arteries and veins, the first equation applies. The second equation applies to the heart due to the 3-D change of the heart. In conclusion, adding the following essential information eliminates the confusion about compliance and elasticity: 1) Definitions of Young’s and Bulk’s moduli to address soft tissues elasticity with 1-D and 3-D deformations and 2) The mathematical reciprocal relationship between a type of compliance and its corresponding modulus. 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.
Tonicity Can Be Expressed in Multiple Ways
Authors: Kuang Serena , Li Xiaonan , Yang Xiaoqi , Walter Stefan 
Published: May 2023

We have provided a definition for tonicity1 to eliminate many issues with the concept2-4 in physiology education and proposed that there are multiples ways to express tonicity1. In this abstract, we prove this hypothesis using logical reasoning. OC0 (the initial osmotic concentration in a solution compartment (S) before osmosis occurs)5 is the key term to be used. If person A and B are playing a game and score 12 and 8 points, respectively, there are many ways (narrative or quantitative) to express the result of the game, such as “A won the game,” “B lost the game,” “A earned 4 more points than B,” “B had 4 points less than A,” “12 to 8” or “3 to 2.” Osmosis in an osmosis system (S1-m-S2) can be viewed as a water-competing game between OC0 (S1) and OC0 (S2) across the membrane (m). If OC0 (S1) and OC0 (S2) equal 300 and 250 (mOsm/L), respectively, then the tonicity between S1 and S2 can be expressed as “S1 is hypertonic to S2.” This also means that any expressions that mean “S1 is hypertonic to S2” are alternate ways to express tonicity, including 300:250, 6:5, Δ OC0 = 300 – 250 = 50 (mOsm/L), π (S1): π (S2), and Δ π = π (S1) - π (S2). These multiple expressions are not exclusive. Among these ways, “00:250” is most informative. Just like A and B can only own their points (12 and 8) and the score (12 to 8) can only be owned by the game, as we have addressed previously1, S1 and S2 own their points (OC0 (S1) and OC0 (S2)) and the owner of the water-competing game (S1-m-S2), not any solution owns tonicity. A tiny difference between the scores of “12:8” and “300:250” or “ Δ π ” is the following: “12:8” shows the result of the game, “300:250” predicts the result of osmosis or “ Δ π ” shows the result of osmosis. In fact, Δ π is the only accurate definition in a list of inconsistent, elusive definitions of tonicity in the literature we presented in a past work2. As long as the truth of tonicity is clear, the multiple expressions of it can be developed without confusion. Hence, it is incorrect to refer to “a solution’s tonicity” or “the tonicity of a solution,” as is commonly seen in the literature and causes great confusion1. References: Kuang et al., The concept of tonicity: Problems and resolutions [Abstract], The FASEB Journal, 2020 34(S1); Kuang et al., A resolution for the inconsistency in the definitions of tonicity [Abstract], The FASEB Journal, 2022 36(S1); Kuang et al., Resolutions to the problems caused by introducing both osmolarity and effective osmolarity [Abstract], The FASEB Journal, 2022 36(S1); Kuang et al., Origin of the term “isotonic” [Abstract], The FASEB Journal, 2022 36(S1); Kuang et al., The concept of osmolarity: Problems and resolutions [Abstract], The FASEB Journal, 2020 34(S1). 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.
How to Study Osmosis If the Membrane Water Moves Across Is Nonideal
Authors: Kuang Serena , Yang Xiaoqi , Li Xiaonan 
Published: May 2023

In our past works, we introduced two fundamental osmosis systems (a simple S-m-H2O and a composite S1-m-S2) to study osmosis1,2, where m is a selectively permeable membrane that separates two fluid compartments. A composite S1-m-S2 can be deconstructed into two simple osmosis systems (S1-m-H2O and H2O-m-S2)1,2. When applying these two fundamental osmosis systems, a given m can either be permeable to water only (an ideal m) or its permeability to one species of non-charged solute particles (SP, e.g., urea) can be ignored. If m' represents a nonideal membrane whose permeability to urea cannot be ignored, then a new research question emerges: how can osmosis be studied in S-m'-H2O and S1-m'-S2, respectively? This abstract provides the answers by logical reasoning. First, S-m'-H2O can be viewed as the overlap of a pure osmosis system with an ideal m (S-m-H2O) and a permeant SP (pSP), urea diffusion system: S-m'-H2O = S-m-H2O + Surea-m'-H2O, so that osmosis and urea diffusion can be studied separately. The former is governed by van ’t Hoff’s law and the latter by Fick’s law. Second, similarly, S1-m'-S2 = S1-m-S2 + S1urea-m'-S2urea. Third, the effect of urea diffusion on osmosis depends on several conditions: 1) In S-m'-H2O, urea diffusion and osmosis are always in opposite directions, so urea diffusion reduces the resulting osmotic pressure (π). 2) In S1-m'-S2, if S1 is hypertonic to S2 and [urea]S1 > [urea]S2, then the diffusion and osmosis are in opposite directions, so the diffusion reduces the resulting osmotic pressure gradient (Δ π). 3) If S1 is hypotonic to S2 and [urea]S1 > [urea]S2, then osmosis and diffusion are in the same direction, so the diffusion augments the resulting Δ π. In conclusion: 1) Deconstruction of an osmosis system that has a nonideal m' allows separate studies of osmosis and pSP diffusion, respectively. 2) The effect of pSP diffusion on osmosis needs to be differentiated according to the type of osmosis systems and the direction of osmosis and pSP diffusion. 3) While the simple S-m-H2O and composite S1-m-S2 are fundamental osmosis systems, S-m'-H2O and S1-m'-S2 are complex passive membrane transport systems that transport both water and pSP. 4) If a given nonideal m' is permeable to two types of pSP (e.g., urea and glucose), then the diffusion system needs to be further deconstructed into a urea diffusion system and a glucose diffusion system. References: Kuang et al., The concept of osmolarity: Problems and resolutions [Abstract], The FASEB Journal, 2020 34(S1); Kuang et al., The concept of tonicity: Problems and resolutions [Abstract], The FASEB Journal, 2020 34(S1). 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.
Chronic cannabigerol administration lowers blood pressure in phenotypically normal mice
Authors: Vernail Victoria , Bingaman Sarah , Raup-Konsavage Wesley , Vrana Kent , Arnold Amy 
Published: May 2023

Cannabigerol (CBG), the precursor of the major cannabinoid compounds synthesized from Cannabis sativa L., has emerged as a novel potential therapeutic target due to its lack of psychoactive effects and efficacy at reducing pain and inflammation in animal models. Despite this, little is known about the safety of CBG, including its impact on cardiovascular function. Our laboratory recently showed that acute CBG administration lowers blood pressure, by over 20 mmHg, in phenotypically normal male mice via an α2-adrenoreceptor mechanism, which could suggest the need for caution in using this compound in healthy individuals. In this study, we tested the hypothesis that CBG can also lower blood pressure in mice when administered chronically. To test this hypothesis, four male C57BL/6J mice were implanted with radiotelemetry probes at 8-10 weeks of age and allowed to recover for 10 days. This approach allows for continuous measurement of blood pressure, heart rate, and locomotor activity in conscious animals. Baseline blood pressure and heart rate were recorded for 24-hours prior to drug treatment. Mice were then administered CBG at a dose previously found to acutely lower blood pressure (10 mg/kg, intraperitoneal) for 14 days, with vital signs recorded for 24-hours at the end of treatment. We found that chronic CBG reduced 24-hour systolic blood pressure by ~5 mmHg (129±3 mmHg baseline vs. 124±2 mmHg post-CBG; p=0.040 via paired t-test), with similar trends for diastolic and mean blood pressure. This depressor effect was accompanied by a significant decrease in heart rate (581±15 bpm baseline vs. 502±19 bpm post-CBG; p=0.003), with no effect on locomotor activity. These overall findings suggest that chronic CBG may produce a small, but significant, decrease in blood pressure in phenotypically normal male mice. The magnitude of chronic CBG depressor effects was smaller than previously observed for acute administration. This could reflect multiple mechanisms including a2-adrenoreceptor desensitization or baroreflex buffering, but this remains to be tested. Regardless, these findings may provide caution for potential hypotensive effects of CBG under normotensive conditions. Funding sources: PA Options for Wellness and Penn State Medical Marijuana Academic Clinical Research Center 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.
Treatment with PFKFB3 inhibitor potentially improves diastolic function and arterial stiffness in PHD2ECKO mice
Authors: Williams Quinesha , Zeng Heng , Besanson Jessie , Cantrell Aubrey , Chen Jian-Xiong 
Published: May 2023

AIMS: Arterial stiffness is a central factor of cardiovascular disease states and etiologies, such as hypertension and heart failure. Currently there is no available therapy to effectively target arterial stiffness. An oxygen sensing protein, prolyl hydroxylase domain-2 (PHD), is an emerging novel target for vascular remodeling. Previous studies have shown that specific deletion of PHD2 in the endothelium (PHD2ECKO) results in upregulation of hypoxia inducible factor (HIF), a crucial regulator of oxygen homeostasis. HIF affects several pathways, such as angiogenesis and energy metabolism. A glycolytic enzyme, 6-phosphofructo-2-kinase/fructose 2,6-biphosphatase 3 (PFKFB3), produces fructose 2,6-biphosphate. This metabolite allosterically activates phosphofructokinase 1 (PFK1), a rate-limiting enzyme of glycolysis. This study investigates the effects of PFKFB3 inhibition on PHD2ECKO mice using (2E)-3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one [3PO]. We hypothesize that treatment with 3PO will attenuate arterial stiffness in PHD2ECKO mice, thus leading to significant improvement in cardiac function. METHODS AND RESULTS: PHD2ECKO and PHD2f/f mice were injected with 3PO (25mg/kg/day) for 14 days i.p. Echocardiographic measurements were performed prior to treatment and at 2 weeks of treatment with 3PO. Blood pressure measurements were performed for three consecutive days of week one and week two.Echocardiography showed improvement of diastolic function in PHD2ECKO mice post-treatment with 3PO. This was exhibited by significant reductions in diastolic diameter and diastolic volume. Pulse wave velocity (PWV) is decreased, while coronary reserve flow (CFR) is increased post-treatment of the PFKFB3 inhibitor. Though these results are not significant, this notably shows some improvement in arterial stiffness. Blood pressure measurements showed improvements in systolic and diastolic blood pressure for PHD2ECKO mice. Systolic and diastolic blood pressure significantly decreased post-treatment of 3PO. CONCLUSIONS: Inhibition of PFKFB3 in endothelium PHD2 deficient mice improves diastolic cardiac function. Though insignificant, there was an improvement of arterial stiffness. Results showed a slight increase in CRF and decrease in PWV. This suggests that the glycolytic pathway can be a therapeutic target in cardiac function and arterial stiffness. This work was supported by National Institute of General Medical Sciences and National Heart, Lung, and Blood Institute (R01HL151536, JX Chen), the National Heart, Lung, and Blood Institute (R56HL164321, H. Zeng). 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 cardioprotective effects of Empagliflozin in Doxorubicin-induced endoplasmic reticulum (ER) stress
Authors: Malik Akshi , Bagchi Ashim , Jassal Davinder , Singal Pawan 
Published: May 2023

The use of doxorubicin (Dox) in cancer patients carries the risk of cardiotoxicity which is associated with an excessive production of reactive oxygen species as well as an imbalance in the redox state affecting mitochondrial functioning, ER homeostasis and protein folding. An accumulation of misfolded proteins triggers the unfolded protein response (UPR) known as ER stress. Subsequently ER-stress induced apoptosis results in loss of cardiomyocytes. Despite clinical trials indicating the benefits of an antidiabetic drug, Empagliflozin (EMPA) in reducing cardiovascular deaths and hospitalization rate in heart failure patients, it remains uncertain whether EMPA exerts a cardioprotective effect on Dox-induced cardiomyopathy (DIC). Herein, we aimed to investigate the effects of EMPA on Dox-induced ER stress and cardiomyopathy. In isolated adult rat cardiomyocytes, Dox (10μM, 24hrs) induced oxidative stress causing the activation of inflammation markers as well as ER-stress markers. Interestingly, EMPA (500nM, 24hrs) treatment prior to Dox was able to reduce oxidative stress; inflammatory markers (IL-1β, TNFα, and TGFβ), and significantly increased the expression of STAT-3. Dox-induced ER-stress activated ER transmembrane proteins and upregulated the expression of various genes, including X-box binding protein 1 (XBP1). The splicing of XBP1 mRNA on Dox treatment generated spliced XBP1 and subsequently up-regulated chaperones like glucose regulated protein 94 (GRP94), glucose regulated protein 78 (GRP78), and/or protein disulfide-isomerase (PDI). These Dox-induced changes in the upregulation of ER stress proteins were blunted by EMPA. EMPA also promoted expression of inositol requiring kinase 1α (IRE1α) which helped in maintaining ER homeostasis. Additionally, EMPA treatment, down-regulated caspase-12 and caspase-3 activation as well as phosphorylation of c-JUN NH2-terminal kinase (JNK), thereby promoting cardiomyocyte survival. These cardioprotective effects of EMPA on the reduction of ER stress in an in-vitro DIC model suggests its therapeutic potential that can occur independent of the effects related to diabetes. Thus, EMPA may contribute to improvements in cardiac damage during Dox mediated stress and inflammation. The recognition of Dox-induced cardiotoxicity as well as a dire need for a cardioprotective agent to be administered in conjunction with Dox is evident and EMPA may prove to be such an agent. Supported by CANUSA grant. 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.
Mitochondrial Ca2+ dynamics differ between the left and right ventricles in murine and porcine hearts
Authors: Sung Jae Hwi , Villanueva Hector , Igualador Ariadna , Prins Kurt , Liu Julia 
Published: May 2023

Despite their differences in metabolism, mechanics, and developmental origin, the right ventricle (RV) is often assumed to function similarly to the left ventricle (LV). Specifically, though Ca2+ transport into mitochondria is well established to play a crucial role in matching cardiac energy production to demand, little is known regarding whether mitochondrial Ca2+ (mtCa2+) handling is distinct in the RV and LV. Our objective was to test the hypothesis that the regulation of mtCa2+ differs in the RV and LV. By isolating mitochondria from RV and LV free wall tissues from wild-type mice and healthy pigs, we compared several parameters indicative of Ca2+-regulated mitochondrial function. Basal mtCa2+ levels were higher in RV mitochondria than in LV mitochondria. When successive boluses of Ca2+ were administered to isolated mitochondria, RV mitochondria took up fewer Ca2+ boluses, showing lower Ca2+ retention capacity. RV mitochondria displayed relatively more protein carbonylation, suggesting oxidative stress. Interestingly, ATP production rate was higher in RV mitochondria relative to LV mitochondria; however, only LV mitochondria exhibited an increase in ATP production rate in the presence of Ca2+. We also compared the protein expression of the subunits of the mitochondrial Ca2+ uniporter complex (MCUC) and the mitochondrial Na+/Ca2+ exchanger (NCLX) and found that levels of the MCUC subunit Essential MCU Regulator (EMRE) and NCLX were higher in the LV than the RV, potentially facilitating more dynamic Ca2+ transport in and out of LV mitochondria. Collectively, these data suggest that mtCa2+ is calibrated to higher but more static levels in the RV, whereas in the LV basal mtCa2+ is lower to ensure dynamic range for physiological stimuli to increase mitochondrial bioenergetics, corresponding to the larger changes in workload experienced by the LV. This study was supported by the National Institutes of Health (1K22HL137901 to Julia C. Liu) and by the Department of Integrative Biology and Physiology (to Jae Hwi Sung). 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.
Caloric adequacy normalizes brain tissue protein turnover in a rat brain injury model
Authors: Curl Casey , Leija Robert , Peck Austin , Arevalo Jose , Osmond Adam , Doung Justin , Miller Benjamin , Horning Michael , Brooks George 
Published: May 2023

Traumatic brain injury (TBI) is a leading cause for hospitalization in America, often having long lasting effects including increased morbidity, mortality and cognitive deficits post recovery. Based on Standard of Care (SOC) treatment, TBI patients are grossly underfed, yet it is unclear how underfeeding effects protein turnover post-TBI. Thus, we designed a study to elucidate the effects of TBI and caloric restriction (CR) on protein dynamics post-TBI. Hypothesis: We hypothesize that TBI would elicit an increased fractional synthesis rate (FSR) in all brain tissue as compared to control, ad libitum (AL) fed animals, while CR would suppress FSR. Thus, we predicted that the CR+TBI animals would have an elevated FSR over CR control but suppressed compared to AL+TBI animals. Methods: Deuterium oxide was used to measure FSR 13-day post TBI in multiple tissues [skeletal muscle, heart, right and left cerebellum, right and left cortex and hippocampus] of Sprague Dawley rats, AL fed control (AL-Con: n=3), AL+TBI (n=6), or CR+TBI (n=5) and CR-Control (n=6). Tissue homogenates were fractionated to isolate the mitochondrial fraction, and cytoplasmic/sarcoplasmic fraction. Pentafluorobenzyl bromide derivatized alanine samples were measured by GC-MS to evaluate ions with m/z 448, 449, 450. FSR was determined using the m/z ion ratios and MIDA. We found that TBI significantly increased FSR over control animals in the left and right cortex (p≤0.05) and suppressed FSR in the cerebellum (p≤0.05). We found that CR in conjunction with TBI caused an increased FSR in the mitochondrial, cytosolic, and whole tissue of the cortical regions of the brain compared to CR control animals (p≤0.05). The increased FSR found with the CR-TBI group was mitigated with ad lib feeding, exhibiting caloric adequacy mitigates the effects of TBI in cortical and cerebral brain regions. This research shows evidence that caloric restriction has a negative impact on brain healing post-TBI. This project was funded by a grant to GAB from the PAC 12 athletic association (CAL-Brooks-17-02) 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.