bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of coronary artery disease on myocardial blood flow during passive heat stress
Authors: Barry Hadiatou , Chaseling Georgia K , D'Oliviera-Sousa Caroline , Iglésies-Grau Josep , Harel François , Pelletier-Galarneau Matthieu , Gagnon Daniel 
Published: May 2023

INTRODUCTION. Extreme heat is associated with a greater risk of cardiovascular mortality in older adults. However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. One possibility is that myocardial oxygen requirements during heat exposure surpass the capacity for myocardial oxygen delivery, thereby predisposing to myocardial ischemia. This may notably occur in individuals with coronary artery disease (CAD), because it reduces the capacity of the coronary arteries to dilate (i.e., coronary flow reserve). However, it is unknown to what extent myocardial blood flow (MBF) increases during heat exposure and whether this increase is altered by CAD. OBJECTIVE. This study tested the hypothesis that passive heat stress increases myocardial blood flow in older adults and that this increase is attenuated in older adults with CAD. METHODS. Healthy older adults (n=19, 68 ± 7 years) and older adults with CAD (n=12, 72 ± 6 years) were passively heated (water-perfused suit) until rectal temperature increased 1.5°C above baseline values. Myocardial blood flow was measured at baseline and at each 0.5°C increment in rectal temperature during heating by positron emission tomography following intravenous infusion of 82-Rubidium. Heart rate (ECG) and blood pressure (automated auscultation) were also measured to calculate rate pressure product (heart rate × systolic blood pressure). MBF reserve (MFR) was calculated by dividing the MBF at 1.5°C by baseline MBF. Adults with CAD were asked to withhold β-blockers, calcium channel blockers and nitroglycerin for 24h prior to the study. RESULTS. At a 1.5°C increase in core temperature, myocardial blood flow increased from 0.85 ± 0.20 to 1.51 ± 0.40 mL/min/g in healthy older adults and from 0.87 ± 0.19 to 1.37 ± 0.48 mL/min/g in adults with CAD. The change in myocardial blood flow at a 1.5°C increase in rectal temperature did not differ between groups (healthy: 0.66 ± 0.31 mL/g/min, CAD: 0.49 ± 0.42 mL/g/min, p=0.25. Furthermore, healthy adults and adults with CAD displayed a similar MFR at an increase in rectal temperature of 1.5°C (healthy: 1.8 ± 0.4 vs. CAD: 1.6 ± 0.6, p=0.25). CONCLUSION. These results demonstrate that passive heat stress increases myocardial blood flow nearly 1.6 times in older adults, and that this increase is not affected by CAD. These results will help determine if the increase in myocardial blood flow during passive heat exposure is sufficient to predispose to myocardial ischemia in individuals with low coronary flow reserve. Canadian Institutes for Health Research, Montreal Heart Institute 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.
Critical role of long non-coding RNAs in excessive erythropoietic response in Monge's disease
Authors: Azad Priti , Zhou Dan , Haddad Gabriel 
Published: May 2023

Excessive erythrocytosis (EE) is a major hallmark of patients suffering from chronic mountain sickness (CMS, Monge’s disease) and is responsible for major morbidity and even mortality in early adulthood. We took advantage of unique populations, one living at high altitude (Peru) showing EE, while another population, at the same altitude and region, shows no evidence of EE (non-CMS). We have built an in-vitro human iPS-derived model system to study the genetic and epigenetic mechanisms related to pathology of excessive erythropoetic response in these Monge's disease patients. Through RNA-seq, we identified and validated the function of a group of long non-coding RNA (lncRNAs) that regulate erythropoiesis in Monge’s disease. Among the lncRNAs, we found that LINC02228 specifically played a critical role in erythropoiesis the CMS cells and non-CMS based on our functional assays in our in-vitro model systems. We observed that LINC02228 has a huge impact on erythriod colony production (>50% reduction in colonies p<0.001 with the control vs LINC02228-KD). Furthermore, we have also assessed the downstream target genes for these lncRNA (Eg. CSNK2B) and mechanism(s) of erythropoetic regulation by these lncRNAs and found an important role and mediation of erythropoetic transcriptional factor GATA1. We conclude that LINC02228 mediate erythropoesis in Monge's diseases through critical downstream effectors (CSNK2B and GATA1). NIH 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.
Gunryeong-tang extracts protect against diabetes and heart dysfunction by reducing levels of inflammation and fibrosis in db/db mice
Authors: TAI AILIN , Yoon Jung Joo , Han Byung Hyuk , Lee Ho Sub , Kang Dae Gill 
Published: May 2023

Diabetes mellitus (DM) is one of the most common metabolic disorders known to result from abnormal secretion of insulin and/or resistance to insulin. DM is characterized by hyperglycemia, decreased function of pancreatic islet cells and reduced insulin secretion. DM causes many types of complications, among which heart complications are a serious cause of death in people with diabetes. Gunryeong-tang (GRT, 君苓湯) is a traditional oriental herbal formula for the treatment of acute and chronic nephritis, which is used to promote water retention and reduce swelling. However, no study has been conducted on the cardioprotective effects of GRT in diabetes, so this study was investigated whether GRT alleviated diabetes and diabetic heart injury in db/db mice. The experiment was conducted for 8 weeks, distributed into four different groups: db/m control, db/db control, db/db treated with vildagliptin (50 mg/kg/day) or db/db treated with GRT (200 mg/kg/day). As a result, GRT has an impact in lowering high blood glucose levels and insulin resistance in db/db mice. GRT significantly improved cardiac function in db/db mice by inhibiting LDH, CK-MB, and CPK. After 8 weeks of GRT-treatment, M-mode echocardiography was performed to confirm whether GRT had effect on cardiac function. GRT significantly up-regulated impaired LV EF and FS in db/db mice. In addition, GRT was also confirmed to improve histopathological changes (hypertrophy, fibrosis and inflammation) and protein expression levels of related factors caused by diabetes. Furthermore, GRT remarkably improved the expression of factors involved in cardiac apoptosis in db/db mice. Taken together, our results suggest that GRT improves cardiac function and diabetic complications through suppression of cardiac fibrosis and inflammation. Therefore, it is believed that GRT can be developed as a new treatment for diabetes, especially heart complications. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1C1C2009542). 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.
Vagal nerve activity and sympathetic nerve activity are suppressed by alpha-2 adrenergic receptor agonists in conscious rats
Authors: Miki Kenju , Ikegame Shizuka , Yoshimoto Misa 
Published: May 2023

Vagal nerve activity (VNA) and sympathetic nerve activity (SNA) have been known to influence each other and changes in their activity directly, but details on this remain unknown. This study used an alpha-2 adrenergic receptor agonist (dexmedetomidine) to study how SNA affects VNA in the conscious state. Electroencephalography, electromyography, electrocardiography, cervical VNA, renal SNA, and catheters for arterial pressure measurement and intravenous drug administration were measured after male Wistar rats were anesthetized and implanted with electrodes. Dexmedetomidine (50 micro g/kg) was intravenously administered in conscious rats. Cervical VNA decreased and reached its lowest values about 10 min after intravenous dexmedetomidine administration. However, renal SNA, electromyography, and heart rate decreased immediately after administration, whereas arterial pressure increased immediately. These results show that alpha-2 adrenergic receptor agonists simultaneously inhibit VNA and SNA. Furthermore, the present data suggest that excessive SNA activation increases norepinephrine release, inducing an increase in the concentration of circulating norepinephrine, which in turn inhibits SNA via negative feedback and suppresses VNA. JST (JPMJMS2023) 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.
Electrophysiological assessment of patients recovered from COVID-19 infection
Authors: Almazidi Sarah , Al-Subieh Ahmed , Al-Sabti Areej , Al-Mutairi Abdullah , Al-Yahya Asmaa , Al-Taweraqi Reema , Al-Dakhil Lina , Al-Ahmari Abdulla , Al-rouq Fawzia 
Published: May 2023

Background: Neurological manifestation associated with Coronavirus-19 (COVID-19) is commonly reported. However, these patients were not routinely referred for electrophysiological testing. Many studies reported abnormalities in nerve conduction studies (NCS) in patients who recovered from COVID-19 infection. Aim: we aimed to investigate the effect of COVID-19 infection on patients who performed NCS prior to the COVID-19 pandemic and after recovering from COVID-19 illness. Methods: A cohort retrospective study was conducted, which included males and females (average age 50.6 years old) participants who performed NCS before the pandemic and were not hospitalized during their COVID-19 illness. We assessed sensory and motor NCS for the ulnar, median, peroneal, tibial, and sural nerves. A total of 14 ulnar and median nerves and six tibial, peroneal, and sural nerves were assessed. Results: All tested parameters were normal in most of our participants. However, there was a significant increase in amplitude and decrease in conduction velocity (CV) in sensory NCS in median nerves ( p <0.005) and ulnar nerves ( p <0.05). There is an increase in amplitudes and a decrease in the CV in the lower limbs' sensory and motor NCS and the motor ulnar and median nerves, but this did not reach a significance level. Conclusion: This is the first study to assess the effect of COVID-19 on the same nerves (before and after COVID-19 infection). Although all NCS parameters were normal, the paired analysis showed that the median and ulnar sensory nerves are the most affected by COVID-19. Standardized electrodiagnostic guidelines are recommended to be established for recovered COVID-19 patients for early diagnosis of neural functions to ensure optimal recovery. This research was not funded. 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.
Sodium density associates with nighttime systolic blood pressure in young healthy adults
Authors: Axler Michael , Lobene Andrea , Kaseman Kathryn , Awayes Yasmine , Lennon Shannon 
Published: May 2023

Cardiovascular disease (CVD) is influenced by diet quality, such that poor diets generally lead to increased risk. In particular, diets high in sodium have been shown to raise blood pressure (BP) and can lead to arterial stiffening subsequently increasing CVD risk. Current sodium recommendations aimed at lowering CVD risk are given in absolute amounts and do not account for total energy intake. This makes it difficult for individuals with greater energy intakes to meet daily recommended targets. Dietary sodium density (i.e., mg sodium/kcal energy) has been suggested to be a stronger determinant of BP than absolute sodium intake; however, the relation between sodium density and vascular health has yet to be studied in normotensive adults. Our objective was to examine the association between sodium density and ambulatory BP and arterial stiffness in young, healthy, normotensive adults. We hypothesized that sodium density would relate to 24-hour BP and arterial stiffness just as absolute sodium intake does. Sixty-two participants (23M/39W, age 27±6 years, BMI 23.4±2.7 kg/m², BP 112±11/69±9 mmHg) recorded their habitual diet for three days and wore an ambulatory BP monitor to assess 24-hour, daytime, and nighttime BP. Arterial stiffness was assessed by pulse wave velocity (PWV) and wave reflection with augmentation index (AIx). Associations between absolute sodium intake and sodium density with BP and stiffness measures were assessed using bivariate and partial Pearson correlations. On average, participants consumed 2029±547 kcals and 3250±1231 mg sodium. Daytime BP was 118±11/70±7 mmHg and nighttime BP was 106±14/58±9 mmHg. Sodium intake (r=0.31, p=0.03) and sodium density (r=0.35, p=0.01) both correlated with nighttime systolic BP but not nighttime diastolic BP nor daytime or 24-hour systolic or diastolic BP. After controlling for age and sex, both sodium intake (r=0.44, p=0.01) and sodium density (r=0.56, p<0.001) remained significantly associated with nighttime systolic BP. There were no significant correlations between sodium intake or sodium density and PWV or AIx (all p>0.05). These findings indicate sodium density is associated with elevated BP, specifically nighttime systolic BP, in healthy young men and women, suggesting sodium density relates to BP as strongly as absolute sodium intake. Supported by NIH Grant 1R01HL145055 and P20GM113125. 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.
Single-cell mRNA expression profiling of chemosensitive locus coeruleus neurons from American bullfrogs
Authors: Amaral-Silva Lara , Santin Joseph 
Published: May 2023

The locus coeruleus (LC) is a cluster of neurons in the midbrain that, among other roles, participates in the control of breathing by sensing CO2 and evoking hyperventilation, which is observed in mammals, amphibians, and reptiles. The LC is considered the major noradrenergic nucleus of the brain, but in addition to norepinephrine, the mammalian LC also produces glutamate and GABA. Yet, little is known about the neurotransmitter phenotypes of chemosensitive LC neurons in other vertebrates. Thus, we investigated the neurotransmitter profile of neurons responsible for CO2/pH chemoreception in American bullfrogs. For that, 19 LC neurons from 5 American bullfrogs ( Lithobates catesbeianus) brains were analyzed. Chemosensitivity was ensured by monitoring the increase of firing in response to hypercapnia (switching from 1.5% to 5% CO2) in whole-cell patch clamp. A hypercapnic response was observed in all neurons recorded, which were then aspirated into the recording pipette and preserved. Single-cell quantitative PCR was performed to measure the mRNA copy number of markers for glutamatergic (glutamate transporter, VGLUT2), GABAergic (GABA catalytic enzyme, GAD1), and norepinephrinergic (norepinephrine biosynthetic enzyme, DBH) neurons. In addition, we measured the expression of genes with a potential role in pH/CO2 sensitivity; KCNK5 that encodes TASK-2, an alkaline-activated K+ channel; ASIC2 that encodes an acid-sensing cation channel; and KCNJ16 that encodes Kir 5.1, a K+ channel inhibited by acidosis. All LC neurons expressed both VGLUT2 and DBH, while GAD1 had a minimal expression, supporting the role of cotransmission using glutamate and norepinephrine in chemosensitive neurons. KCNK5 and ASIC2 were expressed in most neurons, while KCNJ16 was not. This result suggests that TASK-2 and ASIC2 proteins may contribute to CO2/pH chemosensitivity of LC neurons. Moreover, the expression of these pH sensing related genes ( KCNK5 and ASIC2) had expression linearly correlated to the noradrenergic marker DBH ( e.g., when DHB was high, KCNK5 was high and vice versa) but were not correlated to VGLUT2. Our results point to a transcriptional program that links the noradrenergic cell identity, but not the glutamatergic identity, with the capacity to sense CO2/pH. Given the comparable role of LC in regulating blood gases across vertebrates, our results suggest that the cotransmission of norepinephrine and glutamate from chemosensitive LC neurons plays a role in CO2/pH sensing. This research was funded by the Department of Defense (W911NF2010275) and NIH (R01NS114514) 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.
Cystathionine gamma lyase (CSE) deficiency promotes increased contraction of the corpus cavernosum
Authors: Azeez Tooyib , Pierrre Clifford , La Favor Justin 
Published: May 2023

Cystathionine γ lyase (CSE) is the primary enzyme responsible for hydrogen sulfide (H2S) production in the vasculature. Although, it is known that H2S is a vasodilator systemically, little is known about the effect of CSE on the arteries and tissues responsible for erectile function. Adequate relaxation of the pre-penile arteries and corpus cavernosum are important for effective penile erection, while excessive contraction impedes erectile response. The aim of our study was to determine the effect of CSE deletion on pre-penile vessels and erectile tissue reactivity. We hypothesized that CSE deletion will impair vascular relaxation of these tissues. We used 12 CSE KO mice and 12 age matched controls for this study. The mice were fed with normal chow and water ad libitum and sacrificed at 1 year of age. The distal internal pudendal arteries (dIPA), internal iliac arteries (IIA) and corpus cavernosum (CC) were harvested and used for ex vivo functional assessment. Tissue and wire myography studies were carried out to assess adrenergic and endothelium-dependent vasoconstrictions using cumulative dose-responses to phenylephrine (PE), endothelin, U-46619 and electrical stimulation (E-stim). Endothelium-dependent relaxation was assessed by acetylcholine (ACh) and endothelium-independent relaxation was assessed using Sodium nitroprusside (SNP). Na2S was used to assess the vascular reactivity to H2S. Finally, Non-adrenergic non-cholinergic (NANC) transmission was assessed using E-stim; 20V of electrical impulses were delivered to the tissues with frequency ranging from 0.5 to 16Hz following the administration of atropine, guanethidine and pre-constriction with PE. There were no significant differences observed in the relaxation due to ACh, SNP or NANC-stimulation in any tissue type. However, we found that the loss of CSE increased the contraction of the CC in response to electrical stimulation (p=0.024) and U-46619 (p=0.030). These results indicate that chronic deficiency of CSE increases sensitivity to two prominent vasoconstriction pathways in the CC, which may result in increased vascular resistance in the penis rather than the arteries that supply blood to the penis. Chronic H2S deficiency may thus result in impaired erectile function. This work was supported in part by National Institute of Health grant R03DK131242 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.
Metabolic Consequences of Skeletal Muscle Specific High Expression (SM-HE) of mu-Crystallin Following Low-and High-Fat Diet Interventions are Diet and Sex-Specific
Authors: Noland Kaila , Li Yi , Aja Susan , Bloch Robert 
Published: May 2023

mu-Crystallin is a thyroid hormone binding protein but its role in metabolism is poorly understood. Our previous work on mice with skeletal muscle- specific high expression (SM-HE) of mu-crystallin ( Crym-tg), showed a shift towards oxidative metabolism away from glycolysis (13.7%, as measured by RER via indirect calorimetry), as well as increased expression of slow twitch muscle fiber genes as identified via RNA-seq.Here we report the effects of challenging both male and female, Crym-tg and wildtype littermates to low- and high-fat diets (LFD or HFD). Mice were placed on either diet for 16 weeks, and then subjected to QMR for body composition analysis as well as glucose and insulin tolerance tests (GTT and ITT). Mice were then acclimated to CLAMS cages and studied by indirect calorimetry during ad libitum and fast/refeed conditions. Voluntary wheels were then introduced, and indirect calorimetry measures were again collected, GTT and ITT testing was repeated before harvesting tissue for mRNA and protein interrogation.Our results show sex- and diet-specific differences between Crym-tg and WT littermates. Male Crym-tg mice on LFD weigh significantly less than their WT counterparts due to differences in lean mass. Female mice on LFD show no change in overall mass or body composition compared to controls. Female Crym-tg mice on HFD weigh significantly less than WT, again due to changes in lean mass. Males on HFD did not show significant changes in overall mass or body composition. We found no distinct patterns in the parameters monitored by indirect calorimetry that could account for these changes.Following design of a qPCR array for metabolic genes of interest (GOI) (chosen from the RNA-seq data of our previous work in male Crym­-tg mice on normal chow) we saw a distinct difference in expression profiles. Selected GOI showed little variation in mice on LFD. However, dramatically significant differences were seen in mice on HFD. GOIs, when assayed for the male mice, showed a significant decrease in expression across the group for Crym-tg mice as compared to wildtype. Concomitantly, female Crym-tg mice when assayed for the same GOIs showed a significant increase in expression across the group.The work presented here highlights the need for continued studies interrogating sex-specific differences in metabolism. Our results suggest that obesity is not strictly defined by diet and exercise, but also depends on genetic factors, including the levels of expression of Crym. MMPC subcontract from the University of Georgia (R. McInroe, P.I.) 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.