bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Heart Rate Variability by Multiscale Entropy in Spontaneously Hypertensive Rats
Authors: Silva Luiz Eduardo Virgilio , Silva Carlos Alberto Aguiar , Salgado Helio Cesar , Fazan Rubens 
Published: November 2023

Most commonly used approaches to access heart rate variability (HRV) are based on linear models, such as spectral analysis. Recently, much attention has been given to nonlinear methods, because they quantify important additional properties of HRV dynamics. Multiscale entropy (MSE) can quantify the predictability of time series over several time scales, which is demonstrated to be related to neuro‐humoral regulation of cardiac activity. We calculated Sample Entropy over scales 1 to 20 in time series of cardiac interval from spontaneously hypertensive rats (SHR), to identify how hypertension affects the predictability of HR over multiple scales. ECG was continuously recorded during 90 minutes in SHR (N=7) and normotensive Wistar‐Kyoto rats (WKY, N=6) previously (5 days) instrumented with probes that allowed wireless ECG recordings. Beat by beat series of RR were extracted and processed (artifact and missed detections excluded) prior to analysis. Entropy values of SHR are significantly lower compared to WKY for scales four onwards. Total entropy is also significantly lower in SHR (11.6 ± 0.9 vs 16.7 ± 1.2, p=0.008). MSE curve in SHR showed a rapid decrease reaching a plateau after scale 3. In WKY the decrease of MSE was smaller than in SHR, but fully recovered towards the higher scales. The results suggest that mechanisms responsible for long‐term non‐linear dynamics of HRV, such as sympathetic activity and humoral factors, are the most affected in SHR.Support or Funding InformationFAPESP, CAPES, CNPq
CARDIORESPIRATORY CONTROL IN NEWBORN RATS SUBMITTED TO CHRONIC INTERMITTENT HYPOXIA
Authors: Menezes Miguel F. , Zoccal Daniel 
Published: November 2023

Postnatal hypoxia is a major risk factor for the development of cardiorespiratory diseases in adulthood. In this study, we evaluated the effects of postnatal intermittent hypoxia (IH) on baseline cardiorespiratory parameters and on ventilatory responses to hypercapnia. We also verified whether the IH‐induced cardiorespiratory changes were dependent on the DNA hypermethylation. Holtzman newborn rats (P0–1) were subjected to IH (6% O2 every 9 min, 8 hours/day, n= 27) or normoxia (n= 19) during the first 10 days of life and received i.p. injections of decitabine (a hypomethylating agent, 1 mg/kg) or vehicle (control) every 3 days, during 10 days. At 35 day old, mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR), tidal volume (VT) and minute ventilation (VE) were measured at rest and during hypercapnia (7% CO2, 10 min). Exposure to IH increased baseline MAP (95±1 vs 85±4 mmHg), HR (459±7 vs 414±9 bpm), VT (16.2±0.8 vs 10.7±0.4 mL/kg) and VE (1868±95 ml/kg/min vs 1213±86 ml/kg/min) (P<0.05), but not fR. Hypercapnia elevated fR, VT and VE in both groups, but the magnitude of the responses were significantly greater in IH animals (P<0.05). Decitabine treatment during the period of IH exposure was able to prevent the basal cardiorespiratory changes as well as the augmented hypercapnic‐induced ventilatory responses. The data suggest that postnatal IH promotes persistent changes in basal and chemoreflex mechanisms controlling cardiorespiratory parameters by mechanisms involving DNA hypermethylation.Support or Funding InformationSupport by FAPESP (2013/06077‐5).
Carotid body removal markedly improves survival via sympathoinhibition, depressor response and leftward shifting of the pressure‐natriuresis curve in Dahl salt ‐sensitive rats
Authors: Fujii Kana , Saku Keita , Oga Yasuhiro , Nishizaki Akiko , Akashi Takuya , Takehara Takako , Kishi Takuya , Sunagawa Kenji 
Published: November 2023

BACKGROUNDExcessive sympathoexcitation in patients with heart failure is one of the fundamental mechanisms that leads to poor long‐term survival. Carotid body removal (CBR) has shown to reduce sympathetic nerve activity (SNA) and blood pressure (BP) in an animal model of hypertension. The sensitized carotid body is thought to be, in part, responsible for sympathoexcitation in hypertension. We hypothesized that the sensitized carotid body plays a critical role in sympathoexcitation in heart failure. The purpose of this investigation is to examine if CBR reduces SNA, prevents the worsening of heart failure and, in turn, improves survival in a rat model of hypertensive heart failure (Dahl salt‐sensitive rat).METHODSWe randomly allocated 6 week‐old Dahl salt‐sensitive rats fed with high‐salt diet (8% NaCl) into CBR (N=31) or SHAM (N=55). We removed tissues around the carotid bifurcation and established CBR in 7 week‐old rats. We assessed cardiac function (2D‐echo), 24‐hour urinary norepinephrine (uNE) excretion (an index of SNA), and BP. In 14‐week‐old rats, we estimated the pressure‐natriuresis curve by changing the salt intake. Finally, we compared hemodynamics, cardiac histology and survival rate in 16 week‐old rats.RESULTSCBR significantly reduced uNE at 12, 14 and 16 week‐old indicating the sympathoinhibitory effect (Fig. 1), and inhibited the BP elevation from 11 week‐old (Fig. 2). CBR significantly shifted the pressure‐natriuresis curve leftward without changing its slope (Fig. 3). CBR preserved left ventricular (LV) ejection fraction (61±9 vs. 68±8%, p<0.01) and lowered LV end‐diastolic pressure (9±4 vs.5±2 mmHg, p<0.05) suggesting improved cardiac function. In histology, CBR significantly attenuated myocardial fibrosis in both interstitial and perivascular area (p<0.05) (Fig. 4), and reduced the size of cardiomyocyte (804±90 vs. 674±114 μm2, p<0.05). CBR markedly improved the survival rate (Fig. 5).ConclusionCBR markedly improves the survival via sympathoinhibition and depressor response with the leftward shift of the pressure‐natriuresis curve in a rat model of hypertensive heart failure.
Pro‐arrhythmic effects of the cardiac sympathetic co‐transmitter, neuropeptide‐Y, during ischemia‐reperfusion and ST elevation myocardial infarction
Authors: Herring Neil , Kalla Manish , Dall'Armellina Erica , Woodward Lavinia , Lu Chief‐Ju , Banning Adrian , Prendergast Bernard , Forfar John Colin , Choudhury Robin , Channon Keith , Kharbanda Rajesh , Paterson David 
Published: November 2023

Beta‐blockers are the only anti‐arrhythmic drugs that improve mortality post myocardial infarction (MI), but a significant risk of ventricular arrhythmia remains. We have shown that ventricular fibrillation threshold is reduced following high‐level sympathetic stimulation even in the presence of a beta‐blocker due to release of the sympathetic co‐transmitter neuropeptide‐Y (NPY). We hypothesized that exogenous NPY would increase the prevalence of ventricular arrhythmias following ischemia reperfusion in the isolated rat heart. Moreover, we hypothesized that plasma NPY levels would correlate with ventricular arrhythmias following primary percutaneous intervention (PPCI) in patients being treated for ST‐elevation MI (STEMI). In the isolated Langendorff perfused (10ml/min) rat heart NPY (250nM, n=10) significantly increased the prevalence of ventricular arrhythmias (90% v's 20%, p<0.01) following 7 minutes of no flow ischemia compared to control (n=10), and also their severity as measured by arrhythmia scoring (2.0±0.4 v's 0.3±0.2, mean±SEM, p<0.01). In 55 patients presenting with left coronary artery STEMI for PPCI, those with venous plasma NPY levels taken immediately post PPCI above the median (>19 pg/ml) were significantly older (68.0±2.2 v's 58.2±2.5 year old, p<0.01) but had similar cardiovascular risk factors, peak troponin rise and beta‐blocker usage. There was no difference in ejection fraction measured on cardiac MRI after 24 hours (45.3±2.1 v's 46.3±1.9%, n=39) and 6 months (51.8±2.6 v's 55.0±2.9%, n=34) post STEMI between the two groups, and no difference in infarct size (20.4±2.8 v's 17.2±2.6% late Gd enhancement at 6 months). However, over the course of the coronary care unit admission following PPCI, those with NPY levels above the median had a higher prevalence (53.6% v's 25.9%, p=0.03) and a higher severity of ventricular arrhythmias (score: 0.96±0.23 v's 0.33±0.12, p=0.02). NPY may be a novel arrhythmic trigger during ischemia reperfusion and drugs inhibiting NPY or NPY receptors may offer a potential therapeutic opportunity.Support or Funding InformationSupported by the British Heart Foundation and NIHR Oxford Biomedical Research Centre
N‐Acetyl Cysteine Reduces Sympathetic Activation during Acute Intermittent Hypoxia in Healthy Human Subjects: Implications for Obstructive Sleep Apnea
Authors: Jouett Noah , Moralez Gilbert , White Daniel Wade , Tian Jun , Smith Michael L. , Zimmerman Matthew C. , Raven Peter Bernard 
Published: November 2023

The intermittent apneas and hypopneas that occur in Obstructive Sleep Apnea (OSA) patients result in dysregulated chemoreflex control of sympathetic nerve activity (SNA) and contribute to the enhanced cardiovascular disease risk in these patients. Developing novel pharmacological therapies to manage the cardiovascular disease burden of OSA patients would provide significant public health benefit. Prior studies in animal models of OSA have demonstrated that reactive oxygen species (ROS) generated at the peripheral chemoreceptors and in the brainstem results in an exaggerated SNA in response to intermittent hypoxia. This investigation tested the hypotheses that: (a) N‐Acetyl Cysteine (N‐AC) attenuates acute intermittent hypoxia induced sympathoexcitation; by (b) suppressing ROS measured in peripheral venous blood. 28 healthy human subjects were recruited. One hour prior to experimentation, each subject randomly ingested either 70 mg·kg−1 of N‐Acetyl Cysteine (N‐AC, n=16) or vehicle placebo (PL, n=12). Subjects underwent a 20 minute intermittent hypoxia training (IHT) protocol consisting of cyclical end‐expiratory apneas with 100% N2. Three lead electrocardiogram (ECG) and arterial blood pressure (ABP), muscle sympathetic nerve activity (MSNA, n=19) and ROS derived from antecubital venous whole blood using electron paramagnetic resonance (EPR, n=18) spectroscopy were measured. N‐AC decreased MSNA burst frequency during IHT compared to PL (PL 24 ± 2 bursts/min vs. N‐AC: 18 ± 2 bursts/min, P = 0.01) and burst incidence (PL: 35 ± 2 bursts/100HB vs. N‐AC: 25 ± 2 bursts/100HB, P = 0.003). However, N‐AC did not alter EPR spectrum amplitude during IHT compared to placebo (PL: 2.2 × 105 ± 0.6 × 105arbitrary units (AU) vs. N‐AC: 2.7 × 105 ± 0.6 × 105 AU, P = 0.49) in venous blood. Moreover, IHT did not increase ROS concentrations in the peripheral circulation as measured by EPR (P > 0.91). The (a) lack of effect for N‐AC on EPR amplitude and (b) lack of an increase in ROS after IHT are probably indicative of little ROS blood‐brain barrier penetrability/spillover and/or extremely short chemical half‐life of ROS. These data indicate that N‐AC reduces MSNA in response to IHT either centrally by interacting with the central nervous system or peripherally by reducing afferent sensory activity emanating from the peripheral chemoreceptors. This investigation opens the possibility to develop antioxidant‐based pharmacotherapeutics to inhibit the sympathoexcitation associated with OSA and improve the cardiovascular disease burden in this patient population.Support or Funding InformationNational Institute of General Medical Sciences, Grant# P30GM103335National Heart Lung and Blood Institute, Grant #HL106431
The Effects of Remifentanil on the Cardiorespiratory Responses to Severe Arterial Hypoxia in the Rabbit
Authors: Quail Anthony Walker , Cottee David Bruce , Johnstone Janice Maree , White Saxon William 
Published: November 2023

We have previously shown that the central vagus is sensitive to several modern anesthetics (Quail et al 2013, 2015). Remifentanil is an ultra‐short acting synthetic opiate widely used in anesthesia, sedation, obstetrics and analgesia. Opiates can act at the carotid body (McQueen and Ribeiro 1980; Mayer, et al., 1989) and at the commissural nucleus of the solitary tract in the CNS (Zhang et al. 2011), but effects on the integrated components of chemoreflex control are unknown. We examined the hypothesis that components of the cardiorespiratory responses evoked by severe arterial hypoxia (PaO2 < 35 mm Hg) are selectively altered by remifentanil. Six female NZ White rabbits were cannulated via an ear artery and vein (lidocaine 1%). Minute ventilation (VE), tidal volume (VT), respiratory frequency (f), heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (ear SpO2) were measured in conscious rabbits breathing room air, followed by 5 minutes of hypoxia (FiO2 7–8%). After one hour recovery, rabbits breathed room air during i.v. remifentanil (0.1, 0.2, 0.3, or 0.4 mcg/kg/min), followed by matched hypoxia, then recovery breathing room air. Two doses of remifentanil were studied on each of two days, one week apart. Arterial blood samples were taken for blood gas analysis. Data were analysed using repeated measures ANOVA. In rabbits breathing room air remifentanil caused a dose‐related fall in f, VE and HR (P<0.01), while VT and MAP were unchanged. During remifentanil and hypoxia, the reflex bradycardia evoked in conscious rabbits was largely preserved (P<0.05) in a dose‐related manner. The increase in VT remained intact, however the increase in VE was attenuated, with f increasing from a lowered baseline. Remifentanil produced dose‐dependent sedation. We conclude that vagal control of heart rate with remifentanil during severe hypoxia is maintained, while the effects on VE, VT and f appear selective. The data suggest the actions of remifentanil on cardiorespiratory control during hypoxia are mainly central, rather than at the carotid body.Support or Funding InformationJohn Hunter Charitable Research Trust and Hunter Medical Research Institute
Positive airway pressure therapy improves nocturnal beat‐to‐beat blood pressure reactivity in patients with obesity hypoventilation syndrome
Authors: Carter Jason R , Fonkoue Ida T , Grimaldi Daniela , Emami Leila , Gozal David , Mokhlesi Babak 
Published: November 2023

Positive airway pressure (PAP) treatment has been shown to have a modest effect on ambulatory blood pressure (BP) in patients with obstructive sleep apnea. However, there is a paucity of data on the effect of PAP therapy on rapid, yet significant BP swings during sleep, particularly in patients with obesity hypoventilation syndrome (OHS). The present study hypothesizes that PAP will improve nocturnal BP on the first treatment night (titration PAP), and that these improvements will become more significant with 6 weeks of PAP therapy. Seventeen adults (7 men, 10 women; age 50±11 years, BMI 49±2 kg/m2) with OHS participated in three overnight laboratory visits that included polysomnography and beat‐to‐beat BP monitoring via finger plethysmography. Six weeks of PAP therapy decreased partial pressure of arterial carbon dioxide (PaCO2), serum venous bicarbonate, end tidal CO2 during wakefulness, peak transcutaneous CO2 (TcCO2) during sleep, and TcCO2 > 50 mmHg during sleep (p<0.05). Six weeks of PAP therapy, however, did not change pH, partial pressure of arterial oxygen (PaO2), arterial oxygen saturation (SpO2), TcCO2 > 60 mmHg, and spirometry measurements. Six weeks of PAP, but not titration PAP, lowered mean nocturnal BP (p<0.05). When nocturnal beat‐to‐beat BPs were aggregated into bins consisting of at least 3 consecutive cardiac cycles with a >10mmHg BP surge (i.e., Δ10–20, Δ20–30, Δ30–40, Δ>40mmHg), titration and 6‐wk PAP reduced the number of BP surges per hour (time × bin, p<0.05). PAP adherence over the 6‐wk period was significantly correlated to reductions in nocturnal systolic (r=0.713, p=0.001) and diastolic (r=0.497, p=0.043) BP surges. Despite these PAP‐induced improvements in nocturnal beat‐to‐beat BP reactivity, 6‐wk of PAP therapy did not alter daytime BP. In conclusion, PAP treatment reduces nocturnal beat‐to‐beat BP reactivity in patients with OHS, and this improvement in nocturnal BP regulation was greatest in patients with high PAP adherence.Support or Funding InformationSupport from NIH (HL‐119161 and HL‐122919) and Philips/Respironics.
The Ontogenetic Scaling of Metabolic Rate in Wing‐ Polymorphic Gryllus firmus
Authors: Cooper Avril Danielle Juah , Schilder Rudolf J 
Published: November 2023

Extensive study of animal energetics has demonstrated that smaller immature animals tend to have higher body mass‐specific metabolic rates than larger animals, (i.e mice vs. elephants) with metabolic rate scaling approximately as animal body mass to the 3/4 power. In other words, small organisms use more energy per unit body weight than larger ones. The focus of this field has been primarily on vertebrate species and as a consequence it is unclear whether this general tendency applies to insects and insect development. In our study we used respirometry of resting and active metabolism in the flight polymorphic sand field cricket Gryllus firmus to address this question. In nature, G. firmus develops as long‐winged, flight capable and short‐winged, flightless adults that differ in flight muscle and reproductive investment. Therefore, we also examined whether metabolic rates differ during development of the two morphs, i.e. are long‐winged morphs more energetically costly to produce than short‐winged morphs?Support or Funding InformationThe American Physiological Society, Bethesda, MD 20814 National Science Foundation Integrative Organismal Systems Award No. IOS‐1238831
Elevated Carbon Monoxide Production In Marine Mammals
Authors: Tift Michael Scott , St. Leger Judy , Leuker Tim , Ponganis Paul J 
Published: November 2023

Carbon monoxide (CO) is typically thought to be an exogenous gas that has toxic properties from binding tightly to the oxygen‐carrying heme proteins (i.e. hemoglobin and myoglobin). However, the recent discovery of 1) heme degradation leading to endogenous carbon monoxide production, and 2) therapeutic properties from low concentrations of CO has shed new light on the gas. The most promising therapeutic potential has been attributed to CO reducing injuries associated with ischemia‐reperfusion events (e.g. inflammation, apoptosis and cell proliferation). Due to the increased heme protein stores (hemoglobin and myoglobin) and ischemia‐reperfusion events associated with the dive response in diving animals, we investigated endogenous CO levels in the breath (ppm CO) and blood (% carboxyhemoglobin ‐ COHb) of four species of cetaceans (Bottlenose dolphins, short‐finned pilot whales, killer whales and beluga whales) and two pinniped species (northern elephant seals and Hawaiian monk seals). Our findings show that animals with the most elevated heme protein stores (elephant seals, monk seals and beluga whales) have exhaled CO levels (23ppm, 6ppm and 7ppm, respectively) that mimic those seen in human cigarette smokers (> 6 ppm). However, only the elephant seal displayed elevations in blood CO with values as high as 17.6% COHb (5.8X values seen in chronic cigarette smokers). The high values seen in the elephant seals are likely due to elevated erythrocyte turnover in a species with the highest mass specific mammalian blood volume and hemoglobin concentrations. We suggest that these natural elevations in CO potentially serve to protect the animals against injuries related to consistent ischemia‐reperfusion events associated with a lifestyle of breath‐holding and the dive‐response.Support or Funding InformationSociety for Integrative and Comparative Biology (GIAR)PADI Foundation Grant Recipient (2014)
Deiodinase type 3 methylation increases in response to thyroid stimulating hormone in a fasting adapted mammal
Authors: Martinez Bridget , Gemmell Neil , Crocker Daniel E , Ortiz Rudy M 
Published: November 2023

Epigenetic regulation through the methylation of genomic cytosine nucleotides is a crucial component in the regulation of gene expression. DNA methylation in mammalian genomes serves as an important modulator of when and where a gene should be expressed, by primarily targeting 5′‐CpG‐3′ dinucleotides which have been associated with gene regulatory sites, including promoter sequences. Food deprivation in mammals is associated with increases in reverse triiodothyronine (rT3), an inactive form of the metabolism driving thyroid hormone triiodothyronine (T3), as a direct consequence of increases in the expression of the gene deiodinase type 3 (DI3). However, in prolong‐fasted, metabolically active elephant seal pups, cellular thyroid hormone‐mediated components are up‐regulated with fasting duration, while rT3 levels remain low. To address our hypothesis that methylation status of DI3 contributes to the silencing of a gene that would otherwise be expressed under such physiological conditions, we infused early fasted pups with thyroid stimulating hormone (TSH), extracted and treated genomic DNA with sodium bisulfite in an effort to detect and quantify 5‐methylcytosine (5mCs) at single base‐pair resolution. In reference to the genomic sequence of DI3 in elephant seals, prior to infusion with TSH, there is 50% methylation of 15/30 CpG sites in adipose tissue. Twenty‐four hours post infusion with TSH, the degree of methylation of DI3 increases to 93%, with methylation observed in 27/29 CpG sites. Moreover, in muscle, methylation reaches 90%, with 26/29 CpG sites being methylated at only 60 minutes post‐infusion with TSH, suggesting a tissue specific sensitivity. Aside from providing an initial and novel assessment of methylation regulation and status in elephant seals, the data demonstrates a unique adaptation to a methylation pattern where the compacted chromatin structure of DI3 plays a crucial role in suppressing the normal physiological response to fasting otherwise present in most mammals.Support or Funding InformationMinority Health and Health Disparities International Research Training Program, Dennis R. Washington Achievement Graduate Scholarship
Effects of jumping on grasshopper muscle carbohydrate levels
Authors: MacDonald Alexis A , Azher Sharmeen , Kirkton Scott D 
Published: November 2023

As a product of anaerobic respiration, high lactate concentrations are produced in muscle tissue following intense exercise. In 1985, George Brooks hypothesized that lactate may be oxidized by muscles for energy. Although initially controversial, his hypothesis has gained support with mammalian studies showing lactate to be utilized by the muscle (rather than being transported out of the muscle for oxidation in the liver). It is unknown what happens to lactate in an invertebrate. Our research examines the fate of lactate following exercise in Schistocerca americana grasshoppers. Grasshopper jumping muscle is one of the only known invertebrate muscles to produce lactic acid during exercise. Our lab has shown that lactate levels increase dramatically in the grasshopper jumping muscle following hopping and that the lactate remains in the leg rather than being distributed in the body hemolymph or abdominal organs. To determine whether the muscle might be using the lactate as a potential energy source, we used an anthrone assay to measure glycogen and total carbohydrate in the jumping muscle at rest, immediately after jumping, and during recovery. Our initial findings support the hypothesis that lactate is being converted to carbohydrates. Glycogen and carbohydrate concentrations are inversely related to lactate concentrations. Therefore, carbohydrate levels are highest in the muscle of both rested and fully recovered grasshoppers. Carbohydrate concentrations are lowest immediately following jumping and slowly rise during recovery. Similar to what is seen in mammals, our preliminary findings suggest that lactate is used as an energy source within the grasshopper jumping muscle.Support or Funding InformationUnion College Undergraduate Research Committee