bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypocapnia increases heart rate in patients with Postural Orthostatic Tachycardia Syndrome (POTS)
Authors: Ranada Shaun , Karalasingham Kavithra , Baker Jacquie , Hira Rashmin , Wilson Richard , Phillips Aaron , Sheldon Robert , Raj Satish
Published: May 2023

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by chronic orthostatic intolerance and significantly impacts quality of life of patients. POTS predominantly affects women of child-bearing age with an estimated prevalence of up to 1%. POTS is defined by an excessive increase in heart rate (HR) of ≥30 bpm within 10 minutes of upright posture, in the absence of orthostatic hypotension. POTS is associated with chronic symptoms (≥6 months) including hyperventilation (HV) in the form of hyperpnea. HV reduces arterial CO2 (hypocapnia) and worsens tachycardia in POTS. Whether it is hypocapnia that increases HR in these patients is unclear. Studies have not investigated the effects of CO2 on HR due to the confounding effects of posture and ventilation. Objective: We aimed to determine if hypocapnia exacerbates tachycardia in POTS patients. Hypothesis: We hypothesize that hypocapnia will increase HR in POTS. Methods: We conducted a randomized crossover trial of hypocapnic HV vs. eucapnic HV in 13 female POTS patients (34±9 y). Participants completed the supine breathing protocol: 1) HV with resultant hypocapnia, and 2) HV (with end-tidal CO2 (ETCO2) clamped at baseline). Breath-by-breath respiratory (ventilation (VE), tidal volume (VT), ETCO2, end-tidal O2 (ETO2)) and beat-to-beat hemodynamics (HR, stroke volume (SV), cardiac output (CO)) were measured. Data are reported as mean±SD. Paired t-tests were used to compare respiratory and hemodynamic parameters between hypocapnic HV vs. eucapnic HV. Results: During HV, ETCO2 was significantly lower during hypocapnia vs. eucapnia (19.6±3.7 mmHg vs. 37.4±3.5 mmHg; p<0.0001). ETO2 was greater during hypocapnia vs eucapnia (117.4±4.7 mmHg vs. 114.6±3.1 mmHg; p<0.001). There was no difference in VE (22.2±6.5 L/min vs. 22.0±5.1 L/min; p=0.8) or VT (1.4±0.4 L vs. 1.4±0.3 L; p=0.9) between hypocapnia and eucapnia. HR was significantly greater during hypocapnia vs. eucapnia (99±12 bpm vs 82±10 bpm; p<0.001); SV was significantly lower during hypocapnia vs. eucapnia (66±14 mL vs. 74±13 mL; p=0.02); and there was no difference in CO between hypocapnia and eucapnia (6.4±1.3 L/min vs. 6.1±1.6 L/min; p=0.3). Conclusion: Independent of ventilation, hypocapnia increases HR in patients with POTS. Our findings suggests that hypocapnia causes a reduction in SV, perhaps due to increased blood pooling in the capacitance vessels leading to reduced venous return.

This work was supported by Standing up to POTS.

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.
Fentanyl induced disruption of the coordinated reciprocal activity of inspiratory and expiratory respiratory muscles
Authors: Grams Kirstyn , Neumueller Suzanne , Forster Hubert , Buiter Nicole , Hilbert Grace , Pan Lawrence , Lewis Stephen , Hodges Matthew
Published: May 2023

Opioid induced respiratory depression (OIRD) occurs when respiratory pump and/or airway muscle activity are reduced ostensibly due to reduced output from the brainstem respiratory control system, resulting in central (CA) and/or obstructive apnea (OA) and reduced breathing frequency. Although less commonly reported in the literature, ORID may also result from an inappropriate activation of accessory muscles leading to the “Wooden Chest Syndrome” (WCS) -when airflow is limited due to simultaneous activation of inspiratory and expiratory pump and/or airway respiratory muscles to decrease chest wall compliance and inappropriately increase airway resistance. This phenomenon is difficult to directly study in humans, but here we present data from our large animal model (adult female goats). We tested the hypothesis that IV fentanyl would lead to transient dysfunction in respiratory accessory muscles indicative of WCS. We surgically instrumented goats (n=7) with electromyographic (EMG) wires in inspiratory (diaphragm; DIA) and expiratory (Transversus Abdominus; TA) pump muscles, as well as airway dilator (Thyropharyngeus; Thy) and constrictor (Genioglossus; GG) muscles. After >2 weeks of surgical recovery, responses to saline or various doses of fentanyl citrate (25-125 mcg/kg; IV) were tested for 30 min before and up to 90 min after injection. As described in an adjacent poster, particularly over the first several minutes after fentanyl injection, CA and OA were observed in some goats. However, disruption of airflow was primarily associated with increased simultaneous activation of pump and airway inspiratory and expiratory muscles resembling WCS. For most muscles, the rate of rise in muscle activity (an index of firing intensity) increased within 2 minutes following fentanyl injection and remained significantly (P<0.05) elevated up to 90 minutes. During WCS periods, airflow was oscillatory or interrupted suggesting transient closure of the airway. In addition, there were time- and dose-dependent effects on frequency, duration, and total activity of the pump and airway muscles. By 60 minutes post-injection, there were periods of transient return of muscle activity and airflow to at or below baseline values. There was no significant effect of saline on muscle activity. Overall, these data suggest that following fentanyl injection in awake goats, there was an increase in firing of pump and airway muscles which ultimately disrupts the coordinated reciprocal activity of inspiratory and expiratory muscles and contributes to OIRD.

Supported by NIH DA050571

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.
Hypokalemia induced by loss of Kir5.1 initiates WNK-SPAK/OSR1 signaling in Dahl salt-sensitive rats
Authors: Xu Biyang , Mutig Kerim , Klemens Christine , Palygin Oleg , Staruschenko Alexander
Published: May 2023

In the distal convoluted tubule (DCT), Na+ and K+ transport is tightly regulated by Na+-Cl- cotransporter (NCC). A K+-restrictive diet activates NCC through with no lysine (K) kinase (WNK)-Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1) pathway, which increases NaCl retention in the distal tubule. Our previous work demonstrated that deletion of Kcnj16 (the gene that encodes Kir5.1) in Dahl salt-sensitive (SS) rats (SSKcnj16-/-) affecting Na+/K+ transport in the kidney and cause profound hypokalemia with a compensatory increase in both NCC and phospho-NCC (pNCC) activity and expression. Here, we hypothesized that hypokalemia induced by the loss of the Kir5.1 initiates WNK-SPAK/OSR1 signalling and correspondingly upregulate the expression of Na+ transporters without the changes in apical potassium transport or blood pressure increase.12-week-old male SSWT and SSKcnj16-/- rats fed by the normal salt diet (0.4% Na+, 1.36% K+) were used in our studies (N=5 per group). SSKcnj16-/- rats exhibit previously described phenotype with the presence of salt wasting, hypokalemia, and low blood pressure. At the end of the experiment, kidneys were flushed and processed for Western blot, immunofluorescence, and electron microscopy analysis.Electron micrographs of kidney sections of SSKcnj16-/- rats show the significant developing of large WNK body clusters compared to SSWT rats. Total and phosphorylated SPAK signalling were dramatically increased in the DCTs of SSKcnj16-/- rats as determined by immunofluorescent labelling and Western blot. In addition, the expression of cleaved α-ENaC was significantly upregulated in SSKcnj16-/- rats. The expression of apical potassium transporters responsible for renal outer medullary K+ (ROMK) and α- and β4-subunits of Ca2+-activated K+ (BK) channels remained unchanged despite the severe hypokalemia in SSKcnj16-/- rats.Our results demonstrated that hypokalemia induced by loss of Kir5.1 activated the WNK-SPAK/OSR1-NCC pathway and corresponding distal Na+ transport, however it does not impact electrolyte wasting phenotype or promote an increase in blood pressure in SSKcnj16-/- rats.

Funding sources: National Institute of Health Grants R35 HL135749 (to AS), Department of Veterans Affairs grant I01 BX004024 (to AS).

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.
Oxidative stress contributes to attenuated insulin-mediated dilation in the microvasculature of women with a history of gestational diabetes
Authors: Hernandez Paola , Halstead Kristen , Schwartz Kelsey , Brustkern Kaila , Jalal Diana , Stanhewicz Anna
Published: May 2023

Women with a history of gestational diabetes mellitus (GDM) are at greater risk for cardiovascular disease (CVD) and type II diabetes mellitus (T2DM). Endothelium- and nitric oxide-dependent dilation are attenuated in the microvasculature of otherwise healthy women with a history of GDM and this reduction is mediated, in part, by increased oxidative stress. However, whether this attenuation also reduces insulin-mediated microvascular responses in these women is unknown. We hypothesized that 1) insulin-mediated vasodilation would be attenuated, and that 2) antioxidant treatment would increase these responses, in women with a history of GDM compared to matched women with a history of healthy pregnancy (HC). Nine HC (32±6 yrs.) and 8 GDM (33±6 yrs.) participated in 1 experimental visit. Three microdialysis fibers were placed in the ventral forearm for the local delivery of lactated Ringer’s (control), 15mM N G-nitro-L-arginine methyl ester (L-NAME; NO synthase-inhibition), or 5mM ascorbate (non-specific antioxidant). Following baseline measurements, increasing doses of insulin [10-8 -10-4 M] were added to the site-specific perfusates. Red blood cell flux was measured continuously with laser-Doppler flowmetry, and cutaneous vascular conductance was calculated (CVC=flux/MAP) and standardized to maximum (%CVC max; 28mM SNP + 43°C). Subjects with GDM had attenuated insulin-mediated vasodilation (GDM:16.0 ± 3.0 vs. HC: 31.3 ± 4.7 %CVCmax; p= 0.02) at the control site. L-NAME attenuated insulin-mediated dilation in HC (14.7 ± 3.5 %CVCmax, p=0.004) but not in GDM (12.2 ± 1.9 %CVCmax, p=0.48). Local ascorbate perfusion increased insulin-mediated dilation in GDM (27.6 ± 7.2 %CVCmax; p=0.04) but had no effect in HC (p=0.85). These data suggest that women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and that this attenuation is mediated, in part, by increased oxidative stress.

Supported by The UI Fraternal Order of Eagles Diabetes 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.
Relative influence of individual characteristics on critical WBGT limits in young adults (PSU HEAT Project)
Authors: Wolf S. Tony , Havenith George , Kenney W. Larry
Published: May 2023

Critical environmental limits are temperature-humidity thresholds above which heat balance cannot be maintained for a given metabolic heat production. This study examined the association between individual characteristics [sex, body surface area (AD), aerobic capacity (V̇O2max; L∙min-1), and body mass (mb)] and critical environmental limits in young adults. Forty-four (20 M/24 F; 23±4 yr) subjects were exposed to progressive heat stress in an environmental chamber at two low net metabolic rates (Mnet); minimal activity (MinAct; Mnet = 160±35 W) and light ambulation (LightAmb; Mnet = 259±54 W). In 2 hot-dry (HD; <25% rh) environments, ambient water vapor pressure (Pa = 12 or 16 mmHg) was held constant and dry-bulb temperature (Tdb) was systematically increased. In 2 warm-humid (WH; >50% rh) environments, Tdb was held constant at 34 or 36 °C and Pa was systematically increased. The critical wet-bulb globe temperature (WBGTcrit) was determined for each condition. There were no sex differences in WBGTcrit for any condition ( p ≥ 0.21). During MinAct, only mb was retained in a backward linear regression model explaining the variance in WBGTcrit in WH (R2adj = 0.08, p < 0.001), whereas mb and V̇O2max were retained for HD environments (R2adj = 0.09, p < 0.001). During LightAmb, mb and AD were retained in the model for both WH (R2adj = 0.46, p < 0.001) and HD environments (R2adj = 0.22; p < 0.001). These data demonstrate the relative importance of individual characteristics on WBGTcrit during low-intensity weight-bearing (LightAmb) and non-weight-bearing (MinAct) activity in extreme thermal environments.

This work was supported by NIH R01 AG067471.

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.
Oxidative stress induces non-apoptotic cell death and release of placental derived mitochondrial DNA
Authors: Gardner Jennifer , Cushen Spencer , Bradshaw Jessica , Garlotte Isabelle , Zhou Zhengyang , Phillips Nicole , Goulopoulou Styliani
Published: May 2023

Introduction: The placenta, a metabolically active tissue, forms a critical interface between the developing fetus and mother. Stressors such as oxidative stress contribute to placental inflammation, cell death, and release of proinflammatory factors into the maternal circulation. Extracellular mitochondrial DNA (mtDNA) is a proinflammatory factor that can be found in blood circulation in response to cellular stress. Circulating cell-free mtDNA increases during healthy pregnancy and is dysregulated in pregnancies with preeclampsia. Mechanisms underlying the release of mtDNA into circulation from the placenta remain unclear. The objective of this study is to elucidate the relationship between oxidative stress, cell death, and the release of mtDNA from the placenta. We hypothesized that human placental cells exposed to oxidative stressors release mtDNA into the extracellular space via cell death-dependent mechanisms. Methods: BeWo cells (ATCC® CCL-98), a model of placental trophoblast, were treated with the oxidative stressors, rotenone (0.8, 5, 10, 25, 50 μM) or antimycin A (10, 50, 100, 320 μM) and their respective vehicles for 4 hours. Supernatants were collected and the following experiments were performed: absolute real-time qPCR quantification with TaqMan™ probes and chemistry to quantify intracellular and extracellular mtDNA (amplification target: MT-ND5gene) and nuclear DNA (nDNA), assays to measure reactive oxygen species, flow cytometry to assess cell death mechanisms. Results: Exposure of placental cells to antimycin A induced the release of mtDNA (p<0.0001) and nDNA (p=0.024), whilst intracellular mtDNA copy number was unaffected (p=0.62). Antimycin A (320 μM) reduced cell viability (vehicle: 64.44 ± 5.46% vs antimycin A: 18.14 ± 5.78%, p=0.0005), increased non-apoptotic cell death (vehicle: 10.39± 3.11% vs antimycin A (100, 320 μM): 30.51 ± 4.43%, 40.16± 5.08%, p=0.0001), and did not affect apoptosis (p=0.11). In addition, there was no change in the release of mtDNA (p=0.43) or nDNA (p=0.82), cell viability (p=0.94), non-apoptotic cell death (p=0.52), or apoptosis (p=0.85) in cells treated with rotenone. Conclusions: Placental cells exposed to oxidative stressors undergo non-apoptotic cell death and release mtDNA. These responses are only observed at high concentrations of antimycin A, a pharmacological inhibitor of complex III of the electron transport chain (ETC), but not rotenone, an inhibitor of complex I of the ETC, suggesting the presence of cytoprotective or rescue mechanisms against oxidative stressors in the placenta.

NIH R01 HL146562, AHA 22PRE-900431, AHA 22POST-903250, NIH T32 AG 020494

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.
Interoceptive receptive fields and functional architecture of physiological control in the mouse brainstem
Authors: Ran Chen , Boettcher Jack , Kaye Judith , Gallori Catherine , Wang Yandan , Liberles Stephen
Published: May 2023

Our external senses of sight, smell, sound, touch, and taste enable us to perceive the external world. In addition, our viscerosensory system monitors the physiological state of peripheral organs. This bodily sensory system orchestrates multi-organ physiological responses, regulating feeding, drinking, sickness behaviors, and generating the internal senses such as satiety, hunger, nausea, visceral malaise. In comparison to external sensory systems, the principles that define visceral sensory processing remain poorly defined. We developed a two-photon calcium imaging preparation to understand internal organ representations in the nucleus of the solitary tract (NTS), a sensory gateway in the brainstem that receives bodily signals mostly via the vagus nerve. Combining the imaging platform with stimulation of multiple visceral organs, we uncover diverse neuronal responses to internal stimuli, while functionally defined cell-types are highly organized within the NTS. Combining functional imaging with pharmacogenetic manipulations and viral tracing from genetically defined vagal sensory cell types, we show that the highly organized representations of internal senses are generated by vagal axon sorting and higher-order sensory processing within the NTS. Using a newly developed spatially patterned optogenetic stimulation system, we showed that stimulating different spatial domains of the NTS differentially modulates autonomic functions. Together, our study reveals basic coding principles used by the brain to process visceral inputs and sheds light on the treatment of viscerosensory and autonomic diseases, including obesity, diabetes, eating disorders, and neuroimmune diseases.

The work was supported by NIH grants to S.D.L. (DP1 AT009497, R01 DK122976 and R01 DK103703), the Food Allergy Science Initiative, and a Leonard and Isabelle Goldenson Postdoctoral Fellowship, a Harvard Brain Science Initiative Young Investigator Transitions Award, and an American Diabetes Association Postdoctoral Fellowship to C.R. S.D.L. is an investigator of the Howard Hughes Medical Institute.

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.
A comparison between heat and temperate-cool environment regarding changes in core temperature with regular exercise: A meta-analysis of randomized controlled trials
Authors: Okazaki Kazunobu , Toya Atsuya , Igarashi Yutaka
Published: May 2023

Purpose: Previous several meta-analyses reported that regular exercise decreased core temperature. However, those meta-analyses included non-randomized controlled trials and did not consider a difference in environment. This meta-analysis aimed to limit studies to randomized controlled trials (RCTs) and evaluate the differences in effects of regular exercise under heat and cool environment on core temperature. Methods: Inclusion criteria were RCTs involving healthy adults, performing exercise in heat index (HI; according to National Weather Service) ≥27°C as the heat environment group (HEAT) and in HI <27°C as the temperate-cool environment group (NORMAL), performing same exercise protocol on both groups, and reporting core temperature at rest or the end of exercise tests. In statistical analyses, the mean differences ([mean value at postintervention in the HEAT – mean value at baseline in the HEAT] – [mean value at postintervention in the NORMAL – mean value at baseline in the NORMAL]) in core temperature were converted into the Hedges’ g values; these values were pooled, and heterogeneity (i.e., a difference among RCTs) was assessed using a Q value. Results: RCTs evaluating core temperature at rest and the end of exercise tests were 5 studies (100 subjects; mean age, 22 to 28 years) and 7 studies (128 subjects; age, 21 to 28 years), respectively. The duration of intervention ranged from 3 to 12 days. Results of the meta-analyses indicated that the pooled g value in core temperature at rest did not decrease significantly (-0.08 [95% confidence interval: -0.18 to 0.03]), and significant heterogeneity was not contained (Q=8.9; P=0.11); in addition, that the pooled g value in core temperature at the end of exercise tests decreased significantly (-0.63 [95% confidence interval: -1.24 to -0.02]), but significant heterogeneity was contained (Q=18.0; P<0.01). Conclusions: The present study is a finding with few RCTs but indicates that regular exercise under heat environment decreases core temperature at the end of exercise than that under normal environment. However, since the results of the meta-analysis contained heterogeneity, the effect may also depend on other factors.

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.
6-month treatment with galectin-1 improves LGMD2B disease pathology in dysferlin-deficient mice
Authors: Kartchner Braden , Spallino Jonathan , Westhoff Luke , Durham Ethan , Nelson Parker , Hansen Colton , Van Ry Pam
Published: May 2023

Limb-girdle muscular dystrophy type 2B (LGMD2B) is a devastating autosomal recessive disease for which there are no current FDA-approved treatments. Our previous research shows that short-term recombinant human Galectin-1 (rHsGal-1) treatment is effective in improving muscle repair and decreasing fat deposition in the BLA/J mouse model. Our current objective is to determine the efficacy of a long-term (6-month) weekly treatment with rHsGal-1 in improving disease pathology in BLA/J mice. Mice treated weekly with intraperitoneal injections of 2.7 mg/kg rHsGal-1 show significant improvements in the time it takes to cross a 10 mm wide balance beam in comparison with saline-injected mice. Treated mice also show less decline over time in how often they rear on their hind legs while exploring a new environment, which suggests improved pathology of the psoas and gluteus muscles, which are especially affected in the BLA/J model. Oil Red O staining of the psoas muscles shows decreased lipid deposition in the muscle of rHsGal-1 treated mice. Other histological stains show improved pathology in various affected muscles. We conclude that weekly treatment with rHsGal-1 is a promising therapeutic for individuals with LGMD2B.

This research is funded by the Jain Foundation

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.
Epoxyeicosatrienoic Acid Mimics Protect Mesangial Cells from Sorafenib Induced Cell Death
Authors: Mishra Abhishek , El-Meanawy Ashraf , Belayet Jawad , Wang Weicang , Wang Yuxin , Hammock Bruce , Bourg Marcus , Mohammad Rawand , Vik Anders , Imig John
Published: May 2023

Study objective: Sorafenib an antiangiogenic drug which are widely used in cancer treatment, and it inhibits vascular endothelial growth factor (VEGF) and tyrosine kinases (TK)involved in both tumor cell proliferation and angiogenesis. Unfortunately, VEGF and TK inhibitors cause severe kidney glomerular injury and proteinuria. Kidney injury that occurs with sorafenib chemotherapeutic treatment is a major clinical challenge that lacks a drug to revert or reduce this kidney glomerular cell damage. Hypothesis: Epoxyeicosatrienoic acid (EET) mimics reduce the nephrotoxic effects of sorafenib on glomerular mesangial cells. Methodology: Human renal mesangial cells (HRMCs) were cultured at 37˚C in RPMI 1640 medium containing 10% FBS, 100 U/ml penicillin, and 0.1 mg/ml streptomycin. Live cell imaging was performed to monitor real-time cell death activity in HRMCs. Apoptosis was determined using the caspase 3/7 dye and the HRMCs cells were imaged every 2 hours for 72 hours using the Incucyte system. HMRCs were tested under four conditions: 1) Sorafenib (10 μM), 2) Sorafenib (10 μM) plus 8,9-EET analogs (1 μM), 3) Sorafenib (10 μM) plus 8,9-EET analogs (3 μM), 4) Sorafenib (10 μM) plus 8,9-EET analogs (10 μM). Thirteen 8,9-EET analogs were also tested for soluble epoxide hydrolase (sEH) inhibitory activity against human sEH recombinant protein. Results: Sorafenib caused significant cell death and increased caspase 3/7 activity in HRMCs. Nine of the 8,9-EET analogs were ineffective in reducing sorafenib induced HRMC cell death and caspase 3/7 activity. Four 8,9-EET analogs in a dose-dependent manner reduced sorafenib induced cell death in HRMCs. This preliminary structure activity relationship analysis revealed an oxamide group as a bioisostere for the epoxide in the 8,9-position of the fatty acid chain, producing protective effects against sorafenib induced cell death in HRMCs. Gratifyingly, this group lacked significant sEH-inhibitory activity. The 8,9-EET analogs RM-84 and MBD-32 reduced sorafenib induced caspase 3/7 activity by 20-40% in HRMCs. Additional protective action was found with the 8,9-EET analogs MDB-52-I the MDB-52-II which dose dependently reduced sorafenib induced caspase 3/7 activity by 60-90% in HRMCs. Conclusion: Collectively, these findings demonstrate the potential for 8,9-EET analogs as a therapeutic strategy against sorafenib-induced glomerular nephrotoxicity.

Arkansas Research Alliance

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.
Protective effect of Securiniga suffruticosa on Diesel vehicles-derived PM2.5 induces lung and cardiovascular injury
Authors: Han Byung Hyuk , Yoon Jung Joo , Tai Ai Lin , Lee Ho Sub , Kang Dae Gill
Published: May 2023

Respiratory exposure to Particulate Matter (PM), including Diesel exhaust particulate (DEP), causes oxidative stress-induced lung inflammation. Especially, fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) is a serious air pollutant associated with various health problems. DEP and PM2.5 pollutants in the air are enter into pulmonary and even bloodstream, and can be causes of inflammatory disorders that are related with respiratory response. The present study aimed to examine the inhibitory effect of Securiniga suffruticosa (S. suffruiticosa) on DEP-induced lung and cardiovascular diseases. The mice groups are follows; sham group: C57BL6 male mice, DEP group: C57BL6 male mice inhaled DEP, S. suffruiticosa Low group: DEP + 100 mg/kg/day S. suffruiticosa, and S. suffruiticosa High group: DEP + 300 mg/kg/day S. suffruiticosa. Mice inhaled DEP by using nebulizer chamber and were sacrificed 48 hours after final exposure of DEP. Treatment with S. suffruiticosa reduced the expression of inducible CXCL1 and CXCL2 in bronchoalveolar lavage fluid and Muc5ac, ICAM-1, TNF-α, IL-6 mRNA in lung were also attenuated by S. suffruiticosa. In thoracic aorta, DEP increased CAMs, TNF-α and inflammasome markers such as NLRP3, Caspase-1, and ASC. However, S. suffruiticosa suppressed these levels. In HUVECs, S. suffruiticosa inhibited PM2.5 induced production of intracellular reactive oxygen species (ROS); and inhibited the translocation of NF-κB p65 to the nucleus in HUVECs (human umbilical vein endothelial cells). Taken together, this study proved that exposure to PM2.5 induced both lung and vascular inflammation, however, S. suffruiticosa attenuated this injury via the downregulation of the NLRP3 signaling pathway. These findings suggest that S. suffruiticosa may have potential therapeutic benefit against air pollution-mediated lung and cardiovascular diseases.

This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1I1A1A01056937).

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.
Effect of Atractylodes lancea on Cardio-Renal Function in High-Fat-High-Fructose Diet Induced Metabolic Syndrome Rats
Authors: Yang Yun Jeong , Jang Youn Jae , Kim Hye Yoom , Kim Yong Hee , Lee Ho Sub , Kang Dae Gill
Published: May 2023

CRS (Cardio-Renal Metabolic Syndrome) refers to a series of entangled metabolic disorders, including type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease and heart failure, and is associated with obesity, systemic inflammation, and insulin resistance. Atractylodes lancea (AL) is the rhizome of Atractylodes. AL has been found to have diuretic, sedation, antibacterial, anticancer effects. Therefore, in this study, confirmed the effect of AL on improving cardiovascular and kidney function in the metabolic syndrome model. In this experiment, HFHFr were provided to rats for 8 weeks to induce metabolic syndrome, and the OMT (10 mg/kg/day) or AL (100 or 200 mg/kg/day) were administered orally for 8 weeks with HFHFr for 8 weeks to confirm its efficacy. Therefore, a total of 16 weeks of experiments were conducted. To compare Cont with HFHFr, MS categorys were measured. As a result, AL confirmed that HFHr decreased BW, fasting glucose, TG, and abdominal circumference, systolic blood pressure, and increased HDL-C. As a result of measuring insulin and performing OGTT to confirm insulin resistance, which is a major symptom of MS, AAL ameliorates increased insulin levels, and AAL2 significantly decreased blood glucose levels over time. As a result of confirming echocardiography for cardiac function diagnosis, ejection fraction (EF) and fractional shortening (FS) levels were lower in metabolic syndrome than in the control group and significantly improved in the AAL administration group. Staining to confirm the effect of the heart on fibrosis confirmed that collagen accumulation and fibrosis were increased in HFHFr, and improved by AAL compared to the control group. Therefore, these findings suggest that AL improves obesity, insulin resistance, dyslipidemia, and high blood pressure caused by metabolic syndrome, and has a protective effect on heart function decline and fibrosis of the heart and blood vessels.

This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1C1C2095327).

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.
Impact of intravenous propofol and volatile sevoflurane anesthesia on renal function in an experimental pig model of hemorrhage-induced acute kidney injury
Authors: Franzén Stephanie , Frithiof Robert
Published: May 2023

Volatile anesthesia has recently been associated with an independent stimulatory effect on the renal sympathetic nervous system, which causes a reduction in renal blood flow (RBF) and renal excretory function. This anesthetic modality could therefore be a significant contributor to renal injury in the surgical setting. We therefore aimed to investigate the role of anesthetic modality on renal function in an experimental pig model and hypothesized that volatile anesthesia aggravates renal recovery after hemorrhage and resuscitation.Pigs (30±2 kg, 1:1 male-female) were anesthetized with either propofol-fentanyl (P) or sevoflurane-fentanyl (S) and surgically prepared. Renal function and hemodynamics were monitored during a baseline period, a 30-min hemorrhage period, and after 1h recovery after fluid resuscitation with the lost volume (1:1 blood-Ringers Acetate).During baseline, RBF and oxygen delivery (DO2) was significantly lower in the pigs with sevoflurane than propofol anesthesia (RBF P: 191±40 vs S: 130±30 ml min-1, p<0.001; DO2 P: 31±5 vs S: 15±3 ml min-1, p<0.001). Renal vascular resistance (RVR) was also higher in the sevoflurane anesthetized pigs during baseline (P: 0.2±0.05 vs S: 0.5±0.1, p=0.002). There was no statistically different effect of hemorrhage on renal function or hemodynamics between the two anesthetic modalities. Moreover, hemorrhage did not significantly reduce diuresis (P: decreased by 0.7±0.4 ml min-1, p=0.08; S: decreased by 0.4±0.4 ml min-1, p=0.38). After resuscitation, both groups recovered similarly regarding hemodynamics and renal function however, creatinine clearance was still significantly decreased in the sevoflurane group compared with baseline (decreased by 37±31 ml min-1, p=0.02) but recovered in the propofol group. Regarding renal excretory function, no significant differences between the anesthetic modalities were revealed during the experimental protocol.Sevoflurane anesthesia reduced RBF and DO2 and increased RVR. After hemorrhage and resuscitation, creatinine clearance was significantly lower than before the hemorrhage in the sevoflurane group. Even though this reduction in renal perfusion is in alignment with an increase in renal sympathetic nerve activity, no significant impact of anesthetic modality was seen on renal excretory function. However, sevoflurane anesthesia still has an effect on RBF and creatinine clearance. The choice of anesthesia could therefore effect the incidence of acute kidney injury in patients with higher susceptibility for acute kidney injury.

Funding sources: Magnus Bergvall Foundation (2017-02295) and Swedish Research Council (2014-02569 and 2014-07606).

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.
Linkage of NAFLD with diabetes complications
Authors: Shamansurova Zulaykho , Saatov Talat , Rakhmonova Gulzor , Khasanova Gulhayo , Abdiev Ilkhom , Aikhodjaeva Mokhira , Maksutova Nigora
Published: May 2023

Introduction: People with type 2 Diabetes Mellitus (DM2) have high risk and frequency of non-alcoholic fatty liver disease (NAFLD) development. Altered liver function reflected on glycemia level and increased risk of diabetes complications. The aims of our study were try to find relationship between NAFLD, glycemic control, type of treatment and frequency of diabetes complications. Material and methods: 62 people with DM2 admitted in hospital of Republican Specialised Scientific Practical Medical Centre of Endocrinology named after acad. Y.KH. Turakulov, were observed. 32 men and 30 women among them with average age 58.9±0.58 years old and average DM2 duration was 9±2.3 years. In all observed people Body mass index (BMI), total blood count, urine check, glycemia, HbA1c, AlT, AsT, total cholesterol, triglycerides and liver ultrasound were assessed. Liver fibrosis score were calculated according to Fib4 formula. Results: NAFLD were determined in 45.8%, almost half among observed DM2 patients. There were significant differences in BMI (P<0,05), total blood platelets count (P<0,01), HbA1c (P<0,05), blood fibrinogen (P<0,05), triglycerides level (P<0,05) in DM2 with and without NAFLD. Interestingly blood platelets count were found significantly lower in NAFLD group(P<0,001) and Fib4 score were 1.5 times higher (P<0,05) in DM2 group with NAFLD. Analysis of frequency of DM2 complications such as diabetic retinopathy (DR), nephropathy (DN), neuropathy (DPNP) showed more severe stages in NAFLD group. Particularly, DN with proteinuria were detected in 62% with NAFLD and in 35% without; severe DR2 and DR3 were registered in 69% with NAFLD and in 33% without, severe DPNP were diagnosed in 81% with NAFLD and in 74% without NAFLD. Conclusion: NAFLD are frequent future in DM2 and were detected in 45.8% patients, characterized with greater BMI, higher HbA1c, blood fibrinogen and lower platelets number in total blood count and 1.5 times higher Fib4 score. NAFLD associated with more severe stages of diabetes complications and have a great impact on diabetes complication development.

no funding

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.
Differential impacts of pregnancy and lactation on maternal calcium homeostasis: a mathematical modeling analysis
Authors: Stadt Melissa , Alexander Todd , Layton Anita
Published: May 2023

The maternal physiological adaptations during pregnancy and lactation impact almost all tissues and organs, including those involved in calcium homeostasis. Despite having a similar additional calcium demand, maternal adaptations in pregnancy and lactation are different. During pregnancy, the mother’s body increases intestinal absorption of calcium. However, during lactation, intestinal absorption returns to normal levels and the calcium needs of breastmilk are met by increased bone resorption and renal calcium reabsorption. Existing mathematical models of calcium homeostasis do not consider these unique physiological states. Given this observation, the goal of this project is to develop the first pregnancy- and lactation-specific mathematical models of calcium regulation. The resulting models represent how a female body adapts to support the excess demands brought on by pregnancy and lactation. Our computational models reveal how both differential adaptations support calcium delivery to the fetus and breastmilk while maintaining normal calcium ranges in the maternal body.

This work is supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada.

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.
Seasonal Tanning-Induced Increases in Skin Pigmentation Do Not Affect Nitric Oxide-Mediated Vasodilation of the Cutaneous Microvasculature
Authors: Fisher Kat , Kenney W. Larry , Wolf S. Tony
Published: May 2023

Acute ultraviolet radiation (UVR) exposure reduces nitric oxide (NO)-dependent cutaneous vasodilation. Additionally, increased constitutive skin melanin concentrations are associated with reduced NO-dependent cutaneous vasodilation. However, the impact of seasonal tanning-induced increases in skin melanin concentration on NO-dependent cutaneous vasodilation has not been investigated. PURPOSE: To investigate the effect of seasonal tanning-induced increases in skin melanin on the NO-dependent cutaneous vasodilation response to local heating. We hypothesized that NO-dependent cutaneous vasodilation would be reduced in tanned skin relative to untanned skin. METHODS: Three intradermal microdialysis fibers were placed in the ventral upper arm (least sun exposed), ventral forearm (moderately sun exposed), and dorsal forearm (most sun exposed) of seven adults (33 ± 14 yrs; 4M/3F) with light-to-moderate constitutive skin pigmentation. Differences in sun exposure among the sites was confirmed using the melanin-index (M-index; an index of skin pigmentation), measured via skin reflectance spectrophotometry. Lactated Ringer’s solution was perfused through the microdialysis fibers while local heating to 42°C induced cutaneous vasodilation. After attaining a stable plateau in cutaneous blood flow, 15mM NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) was perfused at all sites to quantify NO-mediated vasodilation. Red cell flux was measured using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC=LDF/mean arterial pressure) was calculated for each phase of the local heating response (i.e., baseline, initial peak, local heating plateau, post L-NAME plateau) and expressed as percent maximum (%CVCmax; 28mM sodium nitroprusside + 43°C local heating). RESULTS: M-index was highest (i.e., skin pigmentation was darkest) in the dorsal forearm (50.5 ± 11.8 a.u.) compared to the ventral forearm (37.5 ± 7.4 a.u.; p ≤ 0.03) and upper arm (30.2 ± 5.1 a.u.; p ≤ 0.001). There were no baseline (p ≥ 0.37), initial peak (p ≥ 0.22), post L-NAME plateau (p ≥ 0.12), or maximal CVC (p ≥ 0.23) differences among the three sites. Likewise, the magnitude of the local heating plateau was not different among the three sites (dorsal: 88±17%; ventral: 81±20%; upper: 90±12%; p ≥ 0.16), nor was NO-mediated vasodilation (dorsal: 59±15%; ventral: 54±13%; upper: 55±11.0%; p ≥ 0.79). CONCLUSION: These data suggest that, in contrast to the effects of acute UVR exposure or a constitutively dark skin pigmentation, seasonal tanning-induced increases in skin pigmentation do not alter NO-dependent cutaneous vasodilation responses to local heating.

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 Electronic Cigarette Users Exhibit Reduced Cardiorespiratory Fitness and Associated Increased Cardiovascular Disease Risk
Authors: Simovic Tijana , Matheson Chloe , Cobb Kolton , Heefner Allison , Thode Christopher , Billingsley Hayley , Salmons Hannah , Ahmed Syed Imran , Carbone Salvatore , Garten Ryan , Breland Alison , Cobb Caroline , Nana-Sinkam Patrick , Rodriguez-Miguelez Paula
Published: May 2023

BACKGROUND: Electronic cigarettes (e-cigs) are popular tobacco products that are currently advertised as a safer alternative to traditional cigarettes. Preliminary data, primarily from animal studies, suggests that e-cigs are associated with an increased cardiovascular disease (CVD) risk. Cardiorespiratory fitness is a marker of cardiovascular (CV) health and a predictor of CV mortality, which is diminished in traditional tobacco users. However, the effect of chronic e-cigs usage on cardiorespiratory fitness and associated CVD risk in otherwise healthy individuals without established CVD or CVD risk factor, is currently unknown. PURPOSE: The purpose of this study was to investigate the impact of chronic e-cig use on cardiorespiratory fitness and CVD risk in healthy young adults. METHODS: Ten chronic e-cig users (ECU, 4 males and 6 females; age: 24±3 yr; e-cigs usage 3±1.5 yr.) and ten demographical matched, never users (NU, 4 males and 6 females; age: 22.7±2 yr.) participated in this study. Cardiorespiratory fitness was measured by peak oxygen consumption (VO2peak) via a respiratory gas exchange analyzer during a cardiopulmonary exercise test. CVD risk was calculated using Framingham’s 30-year CVD risk score accounting for 8 risk factors (age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein, presence of diabetes mellitus, hypertension treatment, and smoking status). RESULTS: Chronic e-cig users exhibited significantly lower VO2peak (ECU vs. NU; 30.9±4.9 vs. 37.8±6.4 ml/kg/min; p=0.015) and percent predicted (ECU vs. NU; 85.9±16 vs. 105.4±14 % predicted; p=0.001) when compared to never users. Framingham’s 30-year CVD risk score was significantly higher in ECU than in NU (7.7± 4.8, vs. 2.7±0.8 %; p=0.017). Furthermore, an inverse association was identified between VO2peak and 30-year CVD risk ( r=-0.720; p= 0.030). CONCLUSIONS: For the first time, we have identified significantly reduced cardiorespiratory fitness, a marker of CV health and mortality risk, in chronic e-cig users when compared to never users. In addition, chronic e-cig users exhibit higher CVD risk scores. Results from our study imply a negative effect of chronic e-cig use on CV health in otherwise young, apparently healthy adults. Future studies are warranted to investigate the long-term effects of e-cig use on CV health. Supported in part by a Rapid Response Project NIDA/FDA (PRM).

Supported in part by a Rapid Response Project NIDA/FDA (PRM).

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.
MiR-433-3p Inhibition Alleviates Increased Endothelial Cell Permeability in Diabetes
Authors: Kovacs-Kasa Anita , Walker Samantha , Koseoglu Murat , Brian Annex
Published: May 2023

Hypothesis: miR-433-3p is a potential therapeutic target to reduce the excess endothelial permeability seen in peripheral skeletal muscle of diabetes. Background: Peripheral arterial disease (PAD) is a complication of systemic atherosclerosis that results from occlusions in the large arteries of the leg(s). Though best known as a large vessel disease, patients with PAD also have microvascular disease including excess vascular permeability. Patients with diabetes have an increased risk to develop PAD and more severe symptoms compared to nondiabetic patients with PAD patients. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that modulate gene expression by targeting mRNA post-transcriptionally. Methods: Age-, sex-, and risk factor-controlled plasma samples were selected from a PAD biobank. Plasma samples from non-PAD controls, patients with intermittent claudication (IC), or with critical limb ischemia (CLI), with or without diabetes, were selected and miR-433-3p expression was assessed by RT-qPCR. MiR-433-3p expression was analyzed in human ECs after high glucose (HG) (25 mM) or osmolar control (25 mM Mannitol) treatment under normoxia or hypoxia-serum starvation. ECs were also treated with miR-433 inhibitor or negative control. Endothelial vascular permeability, angiogenesis, and cell viability/survival were tested. Vascular permeability by Evans Blue Dye (EBD) was measured in High Fat Diet (HFD) mice versus C57BL/6 mice treated with 100 μM hind-limb, intramuscular injections of miR-433-3p inhibitor, or scramble. Results: Plasma levels of miR-433-3p were elevated in CLI patients with diabetes. In human ECs, miR-433-3p expression was also elevated after high glucose treatment. Endothelial barrier function was impaired after HG, which was restored by miR-433 inhibition. Similarly, miR-433-3p inhibitor improved angiogenesis and cell survival after HG treatment in ECs. HFD mice demonstrated an increased vascular permeability compared to C57BL/6 mice which was attenuated by miR-433-3p inhibition. Conclusion: These data suggest miR-433-3p’s effect on vascular permeability which may contribute to the very poor clinical course seen in PAD and DM. Improved EC permeability with miR-433-3p inhibition may improve skeletal muscle perfusion and create a novel approach for patients with PAD, diabetes, or both.

NIH 5R01HL150003-03 (BHA) and AHA CDA932159 (AK)

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.