bluuebunny/crossref_metadata_2025 huggingface dataset:
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 Information

Supported 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 Information

National 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 Information

John 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 Information

Support 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 Information

The 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 Information

Society 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 Information

Minority Health and Health Disparities International Research Training Program, Dennis R. Washington Achievement Graduate Scholarship
Heart Rate Response to Anthropogenic Disturbance in the Red‐eared Slider
Authors: Florimon Kelly Lourdes , Williams Cassondra Lee
Published: November 2023

When confronted with a disturbance, most mammals experience a fight or flight response, causing heart rate to increase. Submerged crocodilians, on the other hand, undergo a fright bradycardia, or a reduction in heart rate, which may help conserve oxygen while under water. It is not clear how the red‐eared slider (Trachemys scripta) responds to disturbances in the wild or in a laboratory setting. We hypothesized that turtles would experience an increase in heart rate in response to anthropogenic disturbances, suggesting a fight or flight response. To test this hypothesis, we measured heart rate in eight red‐eared sliders exposed to different disturbances. EKG leads were placed through the plastron above and below the heart and EKG data were collected by a self‐contained EKG data logger glued to the turtle's carapace. The logger was minimally invasive and did not interfere with the turtle's natural movements and activities. We first exposed the turtles to the sudden presence or absence of light when no investigator was present. In a separate experiment, we presented the turtles with a noise disturbance with an investigator present. The behavior of each turtle during these disturbance periods was analyzed using synchronized video recordings. We compared the change in heart rate of turtles that were engaged in similar behavior before, during, and after each disturbance. No significant change in heart rate was observed in response to the light disturbance. In response to the noise disturbance, none of the turtles demonstrated a reduction in heart rate. Post‐noise disturbance heart rate increased significantly compared to pre‐noise disturbance heart rate (p=0.02). The average heart rate before the noise disturbance ranged from 7.31 to 15.72 beats per minute (bpm), while the average heart rate after each noise disturbance ranged from 12.49 to 19.39 bpm. There was an overall average increase of 49.13% in heart rate after the noise disturbance. Although having a fright bradycardia would be advantageous for oxygen conservation, turtles have an extraordinary tolerance for anoxia and lactate accumulation. Therefore, it is reasonable that turtles would experience an increase in heart rate due to a fight or flight response, rather than a drop in heart rate caused by a fright bradycardia.
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 Information

Union College Undergraduate Research Committee
Rapid Onset Vasodilation in the Leg is Greater in Habitual Endurance Runners
Authors: Coolbaugh Crystal , Bush Emily , Sabin Shea , Scott Brent , Damon Bruce , Towse Theodore
Published: November 2023

Although the beneficial effects of habitual physical activity on the peripheral vasculature are well‐established, activity‐dependent differences in the blood flow response to single muscle contractions have been largely ignored. Therefore, the purpose of this study was to determine if habitual endurance running (average training volume > 50 miles/week for ≥ 3 years) alters contraction‐induced rapid vasodilation in a limb‐specific manner. Trained (n = 8, 24 ± 3 years) and untrained (n = 4, 24 ± 1 years) men performed 1‐s maximal voluntary contractions in the leg (dorsiflexion) and forearm (hand‐grip). A physical activity recall questionnaire and 7‐day accelerometer recordings were used to confirm differences in training status between groups (p < 0.001). Anterior tibial and brachial arterial blood flow (ml/min) were measured with Doppler ultrasound for 30‐s prior, during, and 90‐s following the muscle contraction. Trained men demonstrated a greater increase in arterial flow in the leg (peak 5.8 ± 0.66‐fold above rest) compared with untrained men (peak 3.5 ± 0.37‐fold above rest; p = 0.04). In contrast, postcontractile blood flow responses in the arm were similar despite training status (Trained: peak 2.8 ± 0.41‐fold above rest; Untrained: peak 3.2 ± 1.1‐fold above rest, p = 0.86). Our data demonstrate that the magnitude of the postcontractile blood flow response to brief muscle contractions is greater in the legs of habitual endurance runners compared with untrained men. Collectively, these findings indicate that quantification of physical activity is necessary to properly interpret differences in contraction‐induced rapid vasodilation due to aging or disease.

Support or Funding Information

Funding: NIH/NIBIB T32 EB001628; CTSA UL1TR000445
Effects of hypoxia with matched convective O2 delivery on fatigue and O2 on‐kinetics in canine skeletal muscle in situ
Authors: Ferguson Brian S , McDonald James R , Mowry Francesca , Sun Yi , Rasica Letizia , Porcelli Simone , Hogan Michael C , Grassi Bruno , Gladden Bruce
Published: November 2023

PURPOSE

Factors influencing maintenance of force development (i.e., fatigue) remain incompletely understood. Previous research in the perfused canine gastrocnemius‐superficial digital flexor muscle complex (GS) (e.g., Barclay. J Appl Physiol 61(3):1084–90, 1986) has suggested that higher blood flow, independent of O2 delivery diminishes the fatigue rate. The aim of this investigation was to evaluate skeletal muscle fatigue development at two different metabolic rates in the GS while blood flow was varied but O2 delivery held constant.

METHODS

Canine GS (n=14) were surgically isolated and electrically stimulated via the sciatic nerve (8V, 0.2ms duration, 50Hz, 200ms train) generating tetanic contractions at either 2 contractions every 3 seconds (~70% VO2peak, n=7) or 1 contraction every second (~100% VO2peak, n=7). Fractional O2 was manipulated with additional nitrogen to the inspired air for final concentrations of ≈21, 12, and 8% O2. Convective O2 delivery to the muscle [blood flow (Q) x arterial O2 content (CaO2)] was held constant by elevating muscle blood flow via a perfusion pump. Muscle developed force was monitored over 3‐min periods of stimulation (sufficient time for significant fatigue to occur) while O2 and blood gases were measured.

RESULTS

Arterial PO2 prior to the different trials at 70% VO2peak was 105±13, 41±2, and 27±1 torr, and for 100% VO2peak was 101±15, 45±4, and 33±5 torr for 21, 12, and 8% inspired O2 respectively. Convective O2 delivery was not different (p≥0.05) among the three O2 fractions; 70% VO2peak = 202±58, 206±57, and 205±49 mL O2·kg−1·min−1; 100% VO2peak = 282±31, 284±43, and 285±52 mL O2·kg−1·min−1 for 21, 12, and 8% respectively. During the 70% VO2peak trials, fatigue was minor for all conditions with 8% inspired O2 fatigue index (FI) = 5.3±3.1% being greater than during the 21% inspired O2, FI = 1.9±1.2% (p≤0.05). During 100% VO2peak, fatigue was much more marked, 22.5±4.8, 22.3±7.5, and 27.8±2.1% for 21, 12, and 8% trials, but not significantly different across conditions (p≥0.05).

CONCLUSIONS

Blood flow independent of O2 delivery had minimal to no effect on the development of fatigue in isolated perfused skeletal muscle stimulated to 70% VO2peak and 100% VO2peak. This was the case despite large differences in arterial and venous PO2, and therefore, likely mean capillary PO2. These results differ from previous work which found effects of blood flow on fatigue that were independent of O2 delivery.
Prediction of Mountain Marathon Performance with Anaerobic Capacity
Authors: Rogers Michael J , Rietchel Lauren J , Singh Prabhjot K , Foster Ian J , Wookey Alison L , White Matthew D
Published: November 2023

PURPOSE

Anaerobic capacity, aerobic capacity and morphology were assessed for their potential effects on race performance during a 50 km mountain ultra‐marathon.

HYPOTHESIS

It was hypothesized that anaerobic and aerobic capacities would be the best predictors of finishing times in this ultra‐marathon.

METHODS

Ten healthy males were recruited to participate in this study. Their average height was 1.76±0.09 m, body mass was 70.75±8.04 kg, Body Mass Index was 22.9±1.85 kg·m−2, body fat percentage was 21.98±4.75 %, and age was 47.6±11.0 years. The office of research ethics at SFU approved the study and each volunteer gave a signed consent prior to participation. Each volunteer's anaerobic capacity was evaluated using a Wingate test on a seated cycle ergometer and aerobic capacity was assessed by indirect calorimetry with a breath‐by‐breath metabolic cart during an incremental test from rest to the point of exhaustion on a treadmill. Predictions of race finishing times were assessed using both stepwise multiple linear regression as well as ANCOVA with body mass as the covariate. The independent variables included mean power, peak power, minimum power, time to peak power, time to fatigue, body fat percentage, body mass, lean body mass and maximal oxygen consumption (VO2MAX).

RESULTS

During the Wingate test mean power was 531.70±88.92 W, peak power was 854.30±193.97 W, time to peak power was 3.25±2.44 s and rate to fatigue was 18.01±4.93 s. During the incremental treadmill test VO2MAX_ABS was 4.01±0.65 L·min−1 and VO2MAX_REL was56.70±6.24 L·min−1·kg body mass−1. The stepwise multiple linear regression indicated that peak power (R2=0.59, p<0.05) or residuals from peak power plotted as a function of body mass (R2=0.54, p<0.05) were significant predictors of race performance in this mountain marathon.

CONCLUSION

These preliminary results support that in a mountain ultra‐marathon a significant fraction of the variance in performance is predicted by peak power as determined in a Wingate anaerobic test.

Support or Funding Information

Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Foundation for Innovation (CFI)
Exercise pressor reflex response to static and dynamic skeletal muscle stretch
Authors: Venturelli Massimo , Cè Emiliano , Limonta Eloisa , Rampichini Susanna , Bisconti Angela V. , Devoto Michela , Esposito Fabio
Published: November 2023

Passive static stretching (SS), arterial occlusion (C), and the combination of both procedures (SS+C) has been used to stimulate group III and IV afferents of the exercise pressor reflex. However, the effects of dynamic passive stretching (DS) and arterial occlusion (DS+C) on the exercise pressor reflex are not fully elucidated. Therefore, the aim of the present study was to compare central and peripheral hemodynamic response to DS, SS, DS+C, and SS+C.

In twelve healthy volunteers, femoral blood flow (FBF), heart rate (HR), cardiac output (CO), and mean arterial pressure (MAP) were assessed during DS and SS of the quadriceps muscle. The same procedures were repeated with arterial occlusion of lower limb (upper‐thigh cuff inflated at 250 mmHg).

FBF increased significantly in both DS and SS by 365±98 and 377±102 ml/min, respectively. This hyperaemia was reduced during DS+C and SS+C by 11±98 and 5±87ml/min. The increase in HR was similar in all conditions (~4.2 bpm for DS, SS, DS+C, and SS+C; p < 0.05). Likewise, the change in CO was ~0.30 l/min p < 0.05. MAP dropped by −4.7±1.2 and −4±1.4 mmHg (p < 0.05) during DS and SS, while it increased by 3.7±1.6, and 4.8±1.3 mmHg for DS+C and SS+C (p < 0.05).

Data from the current study indicated a similar group III afferents response to DS, SS (i.e., equal HR and CO changes). HR and CO findings during DS+C and SS+C suggested no evidence of interaction between group III and IV afferents. Conversely, the MAP reduced only during DS and SS, because of a limb induced‐hyperaemia.
Transiently augmented endothelium dependent vasodilatory capacity following repeated 6‐hour air dives
Authors: Morgan Richard Garrett , Bergeron Elizabeth , Shykoff Barbara E , Florian John P.
Published: November 2023

Background

Military divers routinely participate in operations that involve long duration (≥ 6hr) air dives at shallow (≤ 60 FSW) depths that are repeated daily until mission completion. These dive operations have been linked to impairments in aerobic exercise performance and orthostatic tolerance after egress from the water. Alterations in endothelium‐dependent vasodilation and blood flow may play a role in cardiovascular dysfunction associated with long duration repeated air dives.

Methods

To test this unexplored hypothesis, we measured reactive hyperemia index (RHI), mean arterial pressure (MAP) and resting heart rate (RHR) using the Endo‐PAT2000 plethysmographic peripheral arterial tone (PAT) device in 11 military divers (21–40y) before and after single 6hr air dives at 15 FSW and 6hr air dives at 15 FSW repeated daily for four days. We compared pre and post RHI, MAP and RHR from a single dive and between repeated dives.

Results

We found no differences in RHI, MAP or RHR following completion of a single 6hr air dive at 15 FSW (all P ≥ 0.39). Over the course of four dives repeated daily, we found a main effect of dive day for RHI (P = 0.03), such that pre‐ and post‐dive RHI increased by at least 30% between dives one and three, but returned to baseline by dive four. There was no effect of dive on RHI, determined by pre‐ and post‐dive testing, during each dive day (P = 0.26). We found no effect of dive or dive day on MAP (all P ≥ 0.15); however, pre‐dive RHR was 4–6 bpm higher on the fourth dive day than the second and first day (all P < 0.01), and post‐dive RHR was ~4 bpm lower than pre‐dive RHR across all dive days (P < 0.02).

Conclusions

These findings demonstrate that repeated shallow air dives lead to transiently augmented vasodilatory capacity with a parallel increase in RHR. Increased RHI may help maintain perfusion to the periphery following immersion‐induced diuresis and subsequent reductions in blood volume, while a compensatory increase in RHR occurs to maintain mean arterial pressure.

Support or Funding Information

NAVSEA DSBDP and ONR
The Impact of Acute Isocapnic Hypoxia on Reactive Hyperemia in Young, Healthy Humans
Authors: Kelsch Elizabeth A , Keller Joshua L , Crecelius Anne R
Published: November 2023

Acute hypoxic exposure results in a number of significant physiological responses, including vasodilation in vascular beds of the skeletal muscle. The objective of this study was to investigate the effects of acute hypoxic exposure on microvascular function in young healthy humans, as determined by reactive hyperemia (RH). We first hypothesized that brief exposure to isocapnic hypoxia just prior to arterial occlusion would exaggerate the reactive hyperemic response, given hypoxic vasodilation may cause an increased oxygen mismatch. Second, we hypothesized continuous isocapnic hypoxia prior to and throughout arterial occlusion would attenuate the reactive hyperemic response given chronic exposure has been linked to vascular dysfunction. We tested subjects between the ages of 20 and 23 (n=6) with three counterbalanced trials: control, prior hypoxic exposure, and prolonged hypoxic exposure. Subjects were monitored for end‐tidal CO2 (gas analyzer), O2 saturation (pulse oximetry), heart rate (ECG) and blood pressure (sphygmomanometry). Forearm blood flow (FBF) measurements using venous occlusion plethysmography were made prior to and following 5 minutes of forearm ischemia (RH). During experimental trials, subjects breathed hypoxic gas to decrease arterial O2 saturation to ~85% and isocapnia was maintained via a rebreathe system. Peak RH FBF was slightly increased after brief hypoxic exposure compared to normoxia (43.2±4.2 vs 40.3±6.2 ml/dl/min). However, in continuous hypoxia, peak RH FBF (39.6±3.9 ml/dl/min) was similar to normoxia. The total area under the curve during RH was similar in all three trials (normoxia: 156±9 ml; brief: 152±6 ml; continuous: 154±14 ml). Continuous hypoxia resulted in increased heart rate as compared to brief hypoxia and normoxia. The present results suggest that a brief period of hypoxia prior to occlusion does not impair RH responses. In addition, in young healthy humans, RH responses are preserved following continuous hypoxia throughout occlusion.

Support or Funding Information

University of Dayton‐ Research Council Grant‐In‐Aid; University Honors Berry Summer Thesis Program
Blunted Arterial Blood Pressure Responses to Whole‐Body Cold Stress in Individuals with Multiple Sclerosis
Authors: Allen Dustin Ryan , Huang Mu Ryan , Frohman Elliot M , Davis Scott L
Published: November 2023

Multiple sclerosis (MS) is a neurological disease in which demyelination disrupts signal transmission and/or integration within the central nervous system. Reduced resting MSNA has been previously reported in MS patients (Keller et al., 2014). The aim of this study was to test the hypothesis that individuals with MS will have blunted sympathetic‐mediated responses to a whole‐body cold stress stimulus compared to healthy controls (CON). Ten subjects with relapsing‐remitting MS (age, 35±7 years old; height: 163±9 cm; weight: 64±12 kg; BSA: 1.7±0.2 m2) and 4 healthy controls (31±5 years old; height: 168±6 cm; weight: 66±14 kg; BSA: 1.7±0.2 m2) participated in the study. Subjects were instrumented with a tube‐lined water perfusion suit in which they were exposed to a thermoneutral (34 °C circulating water) condition for a baseline period of 10 minutes, followed by a 3‐minute whole‐body cold stress (5 °C circulating water) condition. Skin blood flow (laser‐Doppler flowmetry), beat‐to‐beat arterial pressure (photoplethysmography), heart rate (ECG), and mean skin temperature were continuously measured. Cutaneous vascular conductance was calculated from the ratio of laser‐Doppler flux to mean arterial pressure (CVC) and normalized to maximal responses obtained by local heating at 42 °C following cooling (%CVCmax). Mean arterial pressures (MAP) were derived during the final minute of baseline and cooling. There were no differences in ΔLDF flux (CON: −2.83±3.76; MS: −3.73±4.29, p=0.72), ΔCVC (CON: −0.05± 0.06; MS: −0.05±0.06, p=0.89), and Δ%CVCmax (CON: −2.43±3.75; MS: −0.24, p=0.12) from baseline to cooling. However, there was a significant difference in ΔMAP between groups (CON: 12.17±9.70; MS: −0.99±7.00, p=0.01). While cutaneous vasoconstrictor responsiveness was similar between groups, these data suggest individuals with MS exhibit reduced sympathetic‐mediated changes in blood pressure in response to a whole body cold stress.

Support or Funding Information

Project funded by NIH grant (R15 HL117224) and National Multiple Sclerosis Society grants (RG4043A and RG4696A)
Effects of Eccentric Exercise‐Induced Muscle Damage on Endothelial Function and Skeletal Muscle Microvascular Deoxygenation
Authors: Caldwell Jacob Troy , Ade Carl J , Black Christopher D , Wardlow Garrett C , Maggard Sierra F , Branch Patrece A , Hardy Rachel N , Quarshie Alwyn T
Published: November 2023

Unaccustomed eccentric exercise has been shown to result in muscle damage (EIMD) and to decrease maximal aerobic exercise capacity (VO2max). Central and peripheral cardiovascular function mediates VO2 max, but it is unclear whether alterations in endothelial and skeletal muscle microvascular function play a role in the reduced VO2 max seen after EIMD. We tested the hypotheses that EIMD of the knee extensors would: 1) decrease local (femoral artery) and systemic (brachial artery) endothelial‐dependent flow‐mediated dilation (FMD), 2) alter the near‐infrared spectroscopy (NIRS)‐derived muscle microvascular deoxygenation (Δ[HHb]) response during incremental cycling exercise, which reflects the balance between muscle O2 delivery and O2 utilization, and 3) decrease VO2max. To date, five of a planned fifteen participants have completed a brachial and femoral artery FMD test, an index of endothelial‐dependent dilation, followed by an incremental exercise test to exhaustion on a cycle ergometer during which pulmonary VO2 and changes in NIRS‐derived Δ[HHb] were measured. Δ[HHb] was measured in the m. vastus lateralis, was normalized to the total response, and was then expressed as a function of relative work rate and fit using a sigmoid function. Each test was performed prior to (Pre) and 48‐hr after a bout of knee extensor eccentric exercise designed to elicit localized muscle damage (Post). Pre brachial artery FMD was 9.7 ± 8.9% and Post brachial artery FMD was 3.6 ± 7.3% (P = 0.1, Effect size (ES) = 0.3). Pre femoral artery FMD was 7.9 ± 7.4% compared to a Post FMD of 1.0 ± 4.4% (P = 0.1, ES = 1.1). During exercise the sigmoid slope was 35.4 ± 25.6 %/% Pre and 37.9 ± 22.1 %/% Post (P = 0.8, ES = .1) Similarly, the c/d value (i.e., 50% of the amplitude of the Δ[HHb] response was 46.7 ± 102.0 % Pre compared to 36.6 ± 46.7 % Post (P = 0.7, ES = 0.1). Pre VO2max was 3.3 ± 0.64 l·min−1 while Post VO2max was 3.1 ± 0.76 l·min−1 (P = 0.1, ES = 0.3). To date this study is under powered (0.08) and additional participants will be tested and included in the final analysis. The findings from this study will provide insight into macro‐ and microvascular function following EIMD and their association with changes in VO2max.
Parkin‐Mediated Mitophagy in Skeletal Muscle with Aging and Exercise
Authors: Chen Chris , Hood David
Published: November 2023

In skeletal muscle, the progressive age‐related loss of muscle mass and strength is known as sarcopenia. Alterations in skeletal muscle mitochondria are considered to be a contributing factor in this process. When mitochondria are no longer able to sustain the energetic requirements of the cell, selective autophagy (mitophagy) pathways are induced to promote the clearance of damaged mitochondria. In aged muscle, dysfunctional mitochondria generate increased amounts of reactive oxygen species (ROS) and can impair quality control mechanisms that facilitate their removal. It remains unclear if mitophagy mediates this reduced response in aged muscle. Parkin is an ubiquitin ligase involved in mitophagy, but little is known about its function with aging. To evaluate mitophagic signaling in aged muscle, young (3 months) and aged (18 months) Parkin deficient (KO) mice and wild‐type (WT) animals were assigned to three groups: control, acute exercise, or acute exercise plus 2 hours of recovery. Muscle mass was reduced by 46% and 65% respectively in aged Parkin KO and WT mice when compared to their young counterparts. Furthermore, aged WT animals displayed a 25% decrease in whole muscle cytochrome c oxidase activity. This was accompanied by a 40% reduction in State 3 (active) intermyofibrillar mitochondrial respiration in aged WT animals. In response to exercise, both aged Parkin KO and WT mice exhibited ~30% declines in running performance, and increased lactic acidosis by 2.1‐ and 1.4‐fold, respectively. Interestingly, basal mitophagy flux and subsarcolemmal mitochondrial localization of LC3II, p62 and ubiquitin were augmented in both young and aged Parkin KO muscle. Acute exercise increased mitochondrial flux in young animals, but reduced flux in older muscle. Our findings indicate that the expression of mitophagy proteins and their localization to mitochondria are not decreased in aged muscle, even in the absence of Parkin. However, attenuation of exercise‐induced mitophagy in response to aging may contribute to mitochondrial accumulation and dysfunction in aged muscle.

Support or Funding Information

Supported by NSERC.
Differential Agonistic Activities of Angiotensin Peptide Analogs
Authors: Speth Robert C , Sturchler Emmanuel , McDonald Patricia
Published: November 2023

Biased agonism of angiotensin (Ang) peptides may differentiate beneficial from pathophysiological actions of the renin‐angiotensin system. To assess the potential for biased agonism a series of Ang peptides modified at the amino terminal, or carboxy terminal (with Isoleucine8), or with D amino acid substitutions were evaluated for their ability to increase cytoplasmic calcium levels, or to alter cellular impedence using the CellKey system to measure agonism, and also to cause desensitization. The most potent analogs for increasing cytoplasmic calcium were 71 to 2 times more potent (EC50 values) in the calcium assay relative to the CellKey assay in the order N‐Methylaspartate1 Ang II, Gly1 Ang II, D‐Arginine1 Ang III, Sarcosine0, Sarcosine1 Ang II, D‐Alanine1 Ang II, and Ang II. Less potent Ang peptides had potency ratios of calcium activation to CellKey activation of ~ 1 to 0.07. Isoleucine (Ile)8 substituted Ang II analogs had extremely weak ability to increase cytoplasmic calcium and moderately weak ability to alter impedence in the CellKey assay with potency ratios of 0.06 to 0.24. The ability of these Ang peptides to cause loss of responsiveness to a subsequent challenge with Ang II in the CellKey assay largely paralleled their potency, with N‐Methylaspartate1 Ang II, Gly1 Ang II,, Sarcosine0, Sarcosine1 Ang II,, and Ang II being most potent at causing desensitization (EC50 values ~ 1 nM). D‐Arginine1 Ang III, D‐Alanine1 Ang II, D‐Aspartate1 Ang II L‐beta Aspartate1 Ang II had lower potencies to cause desensitization, ~ 3 to 20 fold less potent. Interestingly two of the Ile8 substituted Ang peptides; D‐Alanine1, Ile8 Ang II and D‐beta Aspartate1, Ile8 Ang II displayed abilities to desensitize the response to Ang II with 24 and 47 nM potencies. Since the CellKey system measures an integrated cellular response resulting from both G protein as well as beta‐arrestin signaling, these data are consistent with possible differential agonism of these Ang peptide analogs. These data are consistent with previously noted biased agonistic effects of Ile8 containing analogs of Ang II. Since the most well characterized biased agonist for Ang II receptors, Sarcosine1, Ile4, Ile8 Ang II has a micromolar EC50, D‐Alanine1, Ile8 Ang II and D‐beta Aspartate1, Ile8 Ang II might represent more efficacious beta arrestin biased agonists.

Support or Funding Information

R.C. Speth: NIH HL‐113905; Cardiovascular Neuroscience Research Fund, Nova Southeastern University; President's Faculty Research Development Grant, Nova Southeastern University.
Improvement of the Adipokines Profile and Insulin Resistance in Metabolic Syndrome Patients Induced by Galantamine Activation of Cholinergic Pathway
Authors: Sangaleti Carine Teles , Costa Fernando Oliveira , Moraes Tercio Lemos , Irigoyen Maria Claudia , Bortolotto Luiz Aparecido Teles , Lopes Heno Ferreira , Pavlov Valentin , Tracey Kevin , Consolim‐Colombo Fernanda Marciano
Published: November 2023

Introduction

Galantamine, an acetylcholinesterase inhibitor, has been studied showing beneficial effects in preclinical settings of the Metabolic Syndrome (MetS). There is no evidence of clinical investigations addressing to neuroinflammatory modulation with galantamine in MetS.

Purpose

The aim of this study was to verify the effects of galantamine treatment on adiponectin and leptin levels and insulin resistance in patients with the MetS.

Methods

A prospective, randomized, double‐blind, placebo‐controlled study with 60 patients (30 male), 18–59 years old, that fulfilled the criteria of MetS according to the National Cholesterol Education Program, and met additional inclusion and exclusion criteria was conducted. Patients were randomized in 1:1 ratio to receive placebo or Galantamine capsules at a dose of 8 mg for 4 weeks and 16 mg during 8 additional weeks. Clinical parameters, plasma levels of adiponectin, leptin, insulin and calculation of homeostasis model assessment for insulin resistance (HOMA IR) were performed before randomization (time 0 ‐ T0) and at the end of the study (time 1‐ T1). Two‐way repeated measures ANOVA was used to compare differences between groups and T0 ‐ T1. P<0.05 was considered statically significant.

Results

Prior to treatment with placebo or Galantamine (T0), patients were randomized as follows: age=43±3 vs 41±3 years; body mass index = 34±1 vs 35±1 kg/m2; abdominal circumference = 107±2 vs 108±1 cm; systolic blood pressure =125±2 vs 126±2 mmHg; diastolic blood pressure = 79±2 vs 81±1 mmHg; and heart rate = 70±2 vs 72±1 bpm. No significant alterations in these parameters were observed at T1. At T0 placebo and Galantamine groups had similar levels of adiponectin (8.9±0.2 vs 8.8±3 μg/ml), leptin (32.5±0.3 vs 33.3±0.4 ng/ml) and HOMA IR (3.8±0.3 vs 4.2±0.3). However, plasma adiponectin levels were significantly decreased in placebo group and increased in Galantamine group at T1 (7.0±0.2 vs 9.7±0.4 μg/ml). In contrast, plasma leptin levels and HOMA IR were significantly increased in placebo group and decreased in the Galantamine group at T1 (respectively, 36.9±0.4 vs 25.6±0.3 ng/ml and 6.0±1.2 vs 2.7±0.2).

Conclusion

Our results indicate a previously unrecognized efficacy of Galantamine in regulating adipokines levels and attenuating insulin resistance in patients with MetS

Support or Funding Information

Fundação de Amparo à pesquisa do Estado de São Paulo ‐ FAPESP