bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Chronic Sweetener Intake Affect Learning?
Authors: Morales Esmeralda , Contreras Irazú , Estrada José A.
Published: November 2023

Artificial sweeteners are considered innocuous dietary complements used to replace sugarin a variety of commercial products. These additives are also used for the preventionor treatment of chronic illnesses such as diabetes and obesity, as well as forlosing weight. Among the most commonly used sweeteners we have sucralose, which recent studies have related to showing unwanted effects on metabolism.

Due to the essential demand for glucose to supply the energetic requirements of the central nervous system (CNS), a decrease in its bioavailability disturbs signal conduction in the CNS and alters functions dependent on the specific area of the brain affected. This is particularly relevant for areas where neurogenesisoccurs, such as the olfactory bulb, striatum and hippocampus, which are related to cognitive processes involved in learning and memory formation.

The objective of this study is to test spatial learning and memory through the Morris water mazein female BALB/c mice. Spatial learning in this task involves multiple cognitive components, such as problem solving, enhanced selective attention, formation of internal representations of the external world and storage and retrieval of relevant information. Based on principles for the use of animals in research and education, we used three groups of 8 week‐old mice: a control group (without supplementation), a sucrose group and a sucralose group (with sweetener supplemented in drinking water). The animals were supplemented for 5 weeks. After supplementation, mice were tested in a Morris water maze, where mice were trained on five consecutive days and on tested on day 6.

Our results show significant differences in the amount of time taken to reach the platform, as well as time spent searching in the platform area and number of crossings over the platformarea, between the sucrose group and the sucralose and control groups, with mice from the sucrose group taking more time to reach the platform and spending lesstime in the platform area during training (p<0.001) compared to the control and sucralose groups; however, we did not find a statistical difference among groups on the final day. This situation is interesting, since there appear to be differences in the learning process during training, but those differences disappear by the end of the study period. Whether these differences are due to a modified animal behavior during training or to a compensatory mechanism that may balance an initially apparent learning deficiency requires further investigation related to the temporal course of supplementation and the molecular mechanisms involved. We are currently assessing molecular targets that may be relevant for these processes in our model.
The role of inhibition and excitation in visual attention
Authors: Smith Matthew A , Snyder Adam C , Morais Michael
Published: November 2023

The natural world contains more information than our brain has the capacity to process. We make use of selective attention to filter this information ‐ enhance the relevant and suppress the distracting. While the behavioral improvements due to attention are easy to quantify experimentally, the neural circuits that give rise to these improvements remain unclear. In the visual system, modulation of neural activity due to attention is ubiquitous in measurements ranging from scalp electroencephalography to extracellular recordings from single neurons. A number of recent models of attention have proposed that inhibition may play a key role in modulating the computational abilities of neural networks at the locus of attention. While the fundamental importance of inhibition in the nervous system has been known since Sherrington's work at the turn of the 20th century, the mechanisms by which inhibition and excitation interact in service of neural computation are not well understood. Computations in cortex take place in networks of noisy neurons, and modulation of that noise likely plays an important role in attention. Recent models of cortical networks, employing balanced excitation and inhibition, are able to control the level of noise in the system. One prediction from such a model is that the attended state may be mediated be the activity of inhibitory neurons which serve to both modulate the noise in the network while simultaneously increasing response gain. While such a model is easy to implement, it is difficult to test in awake, behaving animals because extracellular recordings are blind to the cell class of the recorded neuron. We developed a novel method of probabilistically classifying neurons based on multiple aspects of their waveform shape that correspond to known differences between cell classes. Using this method, we were able to achieve a high degree of certainty of the classification of 95% of recorded V4 neurons in two rhesus macaque monkeys performing a demanding spatial attention task. We found that inhibitory neurons had stronger effects of attention than excitatory neurons in three key measures: (1) firing rate modulation; (2) decorrelation of their pairwise spiking response; and (3) the match of their response profile to the task's temporal demands. These results suggest that inhibitory neurons are indeed the recipients of a shared signal during the attentive state, and that this signal leads to a decrease in correlation in the rest of the population. Our results thus provide a network‐level account for the role of inhibition in attention.

Support or Funding Information

NIH Grants EY023456, EY018894, EY022928, EY008098 and DA023428
Blockade of Smad4 SUMOylation impairs spatial learning and memory in rats
Authors: Lee Hsiao‐Yuan , Hsu Wei‐Lun , Ma Yun‐Li
Published: November 2023

We have previously found that the protein inhibitor of activated STAT1 (pias1) gene is differentially expressed between fast learners and slow learners from the water maze learning task with fast learners showing a higher expression level of pias1 in hippocampal neurons. Spatial training also increases PIAS1 expression in rat CA1 area. Further, overexpression of PIAS1 in CA1 neurons enhances whereas knockdown of PIAS1 impairs spatial learning and memory performance in rats. Because PIAS1 is a transcriptional regulator that possesses small ubiquitin‐like modifier (SUMO) E3 ligase activity, in this study, we aimed to examine the mechanism underlying PIAS1‐mediated learning and memory facilitation. Smad4 is a downstream target of transforming growth factor‐beta signaling. Smad4 has been well studied in the immune system, but its role in the brain has been rarely examined. In this study we examined whether Smad4 could be SUMO‐modified by PIAS1 in the brain and whether Smad4 SUMOylation plays a role in spatial learning and memory formation. Our results showed that Smad4 could be SUMO‐modified by PIAS1 at Lys‐113 and Lys‐159 both in cell lines and in rat hippocampus in vivo. Further, water maze training increased the level of Smad4 SUMOylation in CA1 neurons compared with the swim controls. Smad4 SUMOylation is also induced by neuronal activation. On the other hand, transduction of the lenti‐Smad4WT vector did not apparently affect spatial learning and memory, but transduction of the lenti‐Smad4 sumo‐mutant vector (Smad4K113RK159R) significantly impaired spatial learning and memory performance. In future studies, we will identify the downstream genes that are regulated by Smad4 SUMOylation and are involved in spatial learning and memory formation.

Support or Funding Information

This work was supported by Grant No. MOST104‐2320‐B‐001‐002‐MY3 from Taiwan.
Cognitive impairment in adolescents 10–14 years old with Type 2 Diabetes Mellitus risk factors and daily stress
Authors: Flores‐Resendiz Constantino , Benitez‐Arciniega Alejandra D. , Martínez‐Carrillo Beatriz E. , Fernando Shane , Soto‐Piña Alexandra E.
Published: November 2023

Daily Stress (DS) is a low intensity stress that can alter cognitive processes, it modifies the Hypothalamus‐Pituitary‐Adrenal (HPA) axis and may promote the development of Type 2 Diabetes Mellitus (T2DM) risks factors. T2DM cardiovascular changes can lead to prefrontal cortex alterations and cognitive impairment. We hypothesized that DS in adolescents with T2DM risks factors impairs cognition. Our aim was to assess the effects of DS and T2DM risks factors on attention and working memory in teenagers 10–14 years old. We evaluated Body Mass Index, blood pressure, fasting blood glucose, family history of T2DM or hypertension. Neuropsi was used to assess attention and memory. Participants were classified in two groups; High Risk (HR), (n=31) and Low Risk (LR) (n=32). The HR group exhibited significantly poorer scores on attention and memory (p< 0.05) relative to the LR group and a higher, but not significant DS percentage. The proportion of DS in general was higher in girls than in boys (p<0.05), but there were no significant differences between boys and girls relative to memory or attention. Plasma cortisol was lower in girls with DS and cognitive deficits (8.8 ± 1.0 μg/dL, p<0.05) than girls without DS and cognitive deficits. Plasma epinephrine (EPI) in girls was significantly lower (56.8 ± 9.1 pg/mL) than boys with DS (114.9 ± 17.2 pg/mL, p<0.001) and no stress (114.9 ± 17.2 pg/mL, p<0.5). These results suggest that the HPA axis and sympathoadrenal system respond differently to stress related T2DM risk factors and cognitive deficits.

Support or Funding Information

Bridge grant UAEMEX‐UNTHSC

CONACYT
Activation of the Chemo‐ and Cardiopulmonary Reflexes Blunt Baroreflex Sensitivity through Independent Mechanisms
Authors: Petersen‐Jones Humphrey G , Holbein Walter W , Johnson Blair D , Convertino Victor A , Curry Timothy B , Joyner Michael J
Published: November 2023

Background

The baroreflex maintains blood pressure homeostasis by modulating sympathetic activity in response to changes in arterial pressure. Baroreflex sensitivity (BRS) is blunted by activation of either the chemo‐or cardiopulmonary reflex; however, little is known about the interaction of these two reflexes on BRS. We hypothesized that activation of the chemoreflex during stimulation of the cardiopulmonary reflex would attenuate the reduction in BRS.

Methods

10 healthy male volunteers (35±3 years, BMI: 25±1 kg/m2) underwent lower body negative pressure (LBNP) at −15mmHg for 5 minutes to stimulate the cardiopulmonary reflex, with chemoreflex activation (hypoxia; arterial oxygen saturation: 85±1%) and without (normoxia; arterial oxygen saturation: 98±0%). Heart rate (HR; ECG), blood pressure (BP; brachial arterial catheter), oxygen saturation (finger pulse oximeter), and ventilation (expired gases) were recorded continuously. BRS was calculated by arterial pressure waveform analysis (spectrum; WinCPRS) during baseline (BL) and LBNP.

Results

Baseline HR was higher during hypoxia than normoxia (62±2 vs 77±3 bpm, p<0.001) while baseline systolic BP (SBP) was not statistically differentiated between conditions (151±3 vs 149±5 mmHg, normoxia vs hypoxia, p=0.669). During normoxic LBNP, HR increased (62±2 vs 66±3 bpm, p=0.001) and SBP was unchanged (151±3 vs 151±4 mmHg, BL vs LBNP, p=0.464). During hypoxic LBNP, HR remained unchanged (77±3 vs 76±4 bpm, BL vs LBNP, p=0.693) and SBP tended to decrease (149±5 vs 139±6, BL vs LBNP, p=0.067). Baseline BRS was lower during hypoxia than normoxia (15±2 vs 9±1 ms/mmHg, p=0.012). LBNP caused a similar % reduction in BRS during normoxia and hypoxia (−14±9% vs −10±7%, p=0.772).

Conclusions

Contrary to our hypothesis, chemoreflex activation during LBNP does not attenuate the reduction in BRS. This suggests that the cardiopulmonary reflex and the chemoreflex blunt BRS through independent mechanisms.

Support or Funding Information

Funding: W81XWH‐13‐2‐0038
Unilateral carotid body resection in patients with resistant hypertension: a safety and feasibility trial
Authors: Hart Emma C , Ratcliffe Laura E.K , Narkiewicz Krzysztof , Briant Linford J.B. , Chrostowska Marzena , Wolf Jacek , Szyndler Anna , Hering Dagmara , Burchell Amy E , Abdala Ana P , Durant Claire , Lobo Mel , Sobotka Paul A , Patel Nik , Leiter James , Engelman Zoar J.B. , Nightingale Angus K , Paton Julian F.R.
Published: November 2023

When stimulated, carotid bodies (CBs) activate sympathetic activity causing hypertension. In hypertensive animals, CBs generate aberrant tone and their resection lowered blood pressure (McBryde et al. 2013. Nat.Communs 4, 2395). In this first prospective proof of concept study our primary outcome was safety and feasibility of unilateral (u) CB resection in drug resistant hypertensive patients; as a secondary outcome we measured blood pressure over a 12 month period. 15 participants with office blood pressure (OBP) 179±7/106±4 mmHg on 5.7±0.3 anti‐hypertensive drugs were studied at 1, 3, 6 and 12 months after removing either the right (n=11) or left (n=4) CB; the latter was confirmed histologically. Hypoxic ventilatory response, adverse events, office blood pressure (OBP), ambulatory BP, muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) were measured. The procedure was feasible as glomus cells were confirmed histologically in resected tissue from 14/15 patients. The intervention was safe as no serious adverse events or serious sleep apnoeas developed following the resection, and the hypoxic ventilatory drive was maintained. Overall, no change in either OBP or ambulatory BP was found. However, in 8/14 participants, day ambulatory BP was reduced at 3 and 6 months (−23±3, −26±4 mmHg, respectively; P<0.01) post resection and correlated temporally with reductions in MSNA (P<0.05), improved BRS (P<0.05); whole drug (anti‐hypertensive) equivalents were also reduced (P<0.01). Respiratory frequency and the ventilatory response to hypoxia were higher in responders (P<0.05) compared to the non‐responders indicative of heightened carotid body drive in these patients. In conclusion, uCB resection was feasible and safe. In a subset of patients (57%), resection lowered ambulatory BP (an effect that persisted for at least 6 months). Mechanistically, the fall in ABPM was associated with reduced MSNA and improvement in BRS. These data support the presence of aberrant carotid body drive in hypertensive patients, which can be interrupted to treat drug resistant hypertension. Cibiem funded the trial.

Support or Funding Information

Cibiem funded the trial.
Muscle Metaboreflex‐Induced Vasoconstriction of Ischemic Active Muscle is Exaggerated in Heart Failure
Authors: Kaur Jasdeep , Alvarez Alberto , Hanna Hanna W. , Machado Tiago M. , Senador Danielle , Krishnan Abhinav C. , Altamimi Yasir H. , O'Leary Donal S.
Published: November 2023

When oxygen delivery to active muscle is insufficient to meet metabolic demands, metabolites accumulate and stimulate skeletal muscle afferents inducing a reflex increase in blood pressure, termed the muscle metaboreflex. Muscle metaboreflex activation during submaximal dynamic exercise increases arterial pressure predominantly via an increase in cardiac output, as little peripheral vasoconstriction occurs. In heart failure, increases in cardiac output are limited and the mechanisms mediating the metaboreflex‐induced pressor response shift to mainly peripheral vasoconstriction. We recently demonstrated that muscle metaboreflex activation induces sympathetic vasoconstriction in the ischemic active muscle, which limits the ability of the metaboreflex to restore blood flow (Kaur et. al., Am J Physiol Heart Circ 2015). In the present study we tested the hypothesis that this vasoconstriction in the ischemic muscle is exaggerated in heart failure. Changes in hindlimb vascular resistance (calculated as femoral arterial pressure/hindlimb blood flow) were observed during metaboreflex activation (induced via graded reductions in hindlimb blood flow during mild exercise) in the same animals with and without α1‐adrenergic blockade (prazosin; 50 μg/kg) and before and after the induction of heart failure. Thus, each animal was observed in each state and served as its own control. During mild exercise, hindlimb skeletal muscle blood flow must be reduced below a clear threshold before the metaboreflex is engaged. In normal animals, initial flow reductions caused metabolic vasodilation. However, when blood flow was reduced below the metaboreflex threshold, vasoconstriction in the ischemic muscle occurred. In normal animals, α1‐adrenergic blockade did not markedly affect hindlimb blood flow or vascular resistance during exercise however, the metaboreflex‐induced vasoconstriction was abolished indicating that this vasoconstriction was neurogenic. After induction of heart failure, hindlimb blood flow during exercise was reduced by < 20% and hindlimb vascular resistance was substantially elevated. Metaboreflex‐induced vasoconstriction within the ischemic muscle was exaggerated after induction of heart failure. In heart failure, α1‐adrenergic blockade caused substantial hindlimb vasodilation during exercise restoring blood flow to near normal levels. Metaboreflex‐induced vasoconstriction was abolished after α1‐adrenergic blockade. We conclude that in heart failure the ability of muscle metaboreflex to restore blood flow to the ischemic muscle is impaired and this may contribute to exercise intolerance.

Support or Funding Information

NIH‐HL55473
Atrial Arrhythmia and Autonomics in an Intermittent Hypoxia Rat Model of Obstructive Sleep Apnea
Authors: Jones Douglas L. , Bober Sara , Ciriello John
Published: November 2023

Introduction

Obstructive sleep apnea (OSA) is a risk factor for developing atrial fibrillation (AF), but the mechanisms underlying AF are unknown. OSA is characterized by airway obstruction and intermittent hypoxia (IH), which has been implicated in the induction of cardiovascular dysfunction. However, the role of IH in predisposing the atria to AF is not understood.

Hypothesis

This study tested the hypothesis that chronic repetitive IH enhances autonomic responses, and predisposes the atria to AF.

Materials and Methods

Adult, male Sprague‐Dawley rats were exposed to normoxia or repeated cycles of 120 s 21% O2 alternated with 80 s 6.5–8% O2 for 8h/day for 7 days. Rats exposed to 7 days of IH or normoxia had in vivo intracardiac electrophysiology studies to evaluate electrophysiological characteristics and susceptibility to electrical inducibility of AF. Atrial effective refractory periods were determined using programmed electrical stimulation (PES) at two atrial locations. Susceptibility to electrically induced AF was determined using PES with 8 stimuli at basic drive cycle lengths of 150 or 100 ms followed by a sequentially premature single extrastimumus and burst pacing using up to 30, 1 sec burst at 50 Hz.

Results

Rats following 7‐days of IH exposure were more susceptible to electrical induction of atrial arrhythmia than normoxic controls (50% vs 0%, respectively, P < 0.05). This was accompanied by an increase in inducibility in the presence of carbachol which was blocked by atropine and darifenacin. The response to isoproterenol were enhanced in the normoxic but not in the IH rats, and the effects of propranolol were less pronounced in the IH rats.

Conclusions

We have demonstrated for the first time that repeated exposure to IH in rats produced enhanced sensitivity to atrial arrhythmias. These novel findings implicating IH as a critical promoter of AF in an OSA model. Accentuation with cholinergic agonists and blockade with nonspecific and M3 specific antagonists is consistent with sensitivity to parasympathetic activation which is known to predispose the atria to AF. The diminished response to sympathetic agents suggests a potential desensitization to adrenergic activation in the IH rats. These novel findings provide an indication of the importance of IH in OSA and susceptibility to atrial arrhythmia and potential for novel therapies in OSA.

Support or Funding Information

Supported in part by the Heart and Stroke Foundation of Ontario
HMB Supplementation Effects on High‐Resolution Skeletal Muscle Diffusion Tensor Imaging and Intramyocellular Fat Changes during High Intensity Military Training
Authors: Hoffman Jay R , Gepner Yiftach , Stout Jeffrey R , Hoffman Mattan W , Ben‐Dov Daniel , Funk Shany , Daimont Ido , Shelef Ilan , Rosen Philip , Avital Guy , Chen Yacov , Frankel Hagai , Ostfeld Ishay
Published: November 2023

The purpose of this study was to examine the effect of β‐hydroxy‐β‐methylbutyrate Free Acid (HMB) supplementation on muscle morphological and muscle lipid changes during highly intense military training. Thirteen soldiers from an elite combat unit were randomly assigned to either a HMB (n=6) or placebo (PL; n=7) group. Soldiers were provided with 3 g·day−1 of either HMB or PL for 23 days. During the final week of supplementation (days 18 – 23) soldiers participated in extreme physical training, which included night navigation of 6 – 8 hours across difficult terrain with approximately 35 kg of equipment on their back. During daylight hours, soldiers remained in camouflaged positions with minimal recovery. Due to a severe environmental stress (37°C and a sand storm) navigational training was performed on only the first two evenings of the week. Still, soldiers continued to be subjected to excessive physical training. During the 6 days of intense training the soldiers slept a total of 22.5 hours (3.8 ± 3.0 h per night). Prior to and following the supplementation period participants were assessed using a 3‐Tesla magnetic resonance imaging (MRI), which included diffusion tensor imaging (DTI) sequence for muscle fiber tracking analysis. Changes of intramyocellular fat percent, muscle volume, intramyocellular fat, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Data was analyzed using a two‐way mixed factorial ANOVA. To complement null hypothesis testing, magnitude based inferences were examined to provide inferences on the true effects HMB may have had on muscle morphological, intramyocellular fat and DTI variables, compared to PL, calculated from 90% confidence intervals. Following the 23‐day supplementation period a possible increase was noted for changes in muscle volume for adductor magnus for HMB (77% likelihood for an increase). Differences in muscle volume for the vastus lateralis, rectus femoris and semitendinosus between HMB and PL were unclear. A possible decrease in intramyocellular fat was noted in the rectus femoris (73% likelihood), but a likely increase in intramyocellular fat was observed in the adductor magnus (83% likelihood) in HMB compared to PL. The effect of HMB on FA in all muscles measured were unclear compared with the effect of PL. In addition, HMB ingestion resulted in a likely increase in ADC in the vastus lateralis only (86% likelihood) compared to PL. Other comparisons between HMB and PL for ADC were also unclear. In summary, short term HMB ingestion prior to intense military training appeared to provide some benefit for maintaining muscle volume but appeared to have only minimal influence on DTI responses.

Support or Funding Information

Metabolic Technologies Inc.
EFFICACY AND SAFTEY OF SIX‐WEEKS OF PRE‐WORKOUT SUPPLEMENTATION IN RESISTANCE TRAINED RATS
Authors: Harris Michael Brennan , Canakis Justin Paul , Valle Nicholas Brennan , Konztias Christina L
Published: November 2023

Pre‐workout supplements contain a variety of compounds to improve performance, muscle strength and growth. However, efficacy and safety of many of these supplements is unknown. The purpose of this study is to determine whether 6 weeks of pre‐workout supplementation in rats undergoing a resistance training program significantly improves performance without any adverse effects on kidney or vascular function. 3 month‐old, male, F344 rats were divided into two groups (n=12/group): 1) control (CTRL) and supplemented (SUP). The SUP group was given Pro Supps Mr. Hyde™—a pre‐workout that contains 2–3 times the amount of caffeine than other brands. Resistance training consisted of climbing a 1 m wire ladder, at an 85° angle, 3d/wk for 6 weeks with increasing weight added to the tail. Aortic dose response curves to phenylephrine (PE, 10−7‐10−4 M), sodium nitroprusside (SNP, 10−8‐10−5 M), and acetylcholine (ACh, 10−7‐×10−5 M) were constructed. Two‐way ANOVA indicated a significant main effect of supplementation on the amount of weight lifted. No differences in body weight or muscle weight were observed. No changes in vascular function or urinary creatinine levels were observed. These data suggest that 6 weeks of pre‐workout supplementation in rats undergoing resistance training was moderately effective by increasing the amount lifted without a significant change in muscle size. Furthermore, no safety concerns related to kidney or vascular function were indicated following 6 weeks of use.
Peripheral Opioid Receptors Contribute to Exercise‐Induced Analgesia in Rats with Chronic Widespread Pain
Authors: Daniels Abigale B. , MacGregor John B. , Kleifgen Sarah L. , Leal Anna K.
Published: November 2023

Fibromyalgia is characterized by chronic widespread musculoskeletal pain. Exercise has been shown to cause both analgesia and hyperalgesia in patients with fibromyalgia. Evidence suggests endorphins acting on central opioid receptors produce exercise‐induced analgesia, but the role of peripheral opioid receptors has not been investigated. We tested the hypothesis that peripheral opioid receptors contribute to exercise‐induced analgesia in a rat model of fibromyalgia. Chronic widespread pain was induced by acidic saline (pH 4) injections into the right gastrocnemius muscle of female Sprague Dawley rats. Control rats (n=10) then underwent four weeks (5 days/week; 30 min/day) of moderate‐intensity treadmill running. Treated rats (n=5) received injections of naloxone (120 μg), a nonspecific opioid receptor antagonist, in both gastrocnemius muscles prior to running. Mechanical hyperalgesia was quantified by measuring mechanical withdrawal threshold with von Frey filaments before and after each exercise bout. Changes in mechanical withdrawal threshold before and after running for control rats (week 1: 9 ± 5 mN; week 2: 10 ± 5 mN; week 3: 20 ± 5 mN) were significantly different from decreases in mechanical withdrawal threshold in the naloxone‐treated group (week 1: −13 ± 9 mN; week 2: −18 ± 8 mN; week 3: −13 ± 8 mN; all p<0.05). Values for week 4 were not significantly different between control (11 ± 5 mN) and treated (5 ± 6 mN; p>0.05). Findings suggest peripheral opioid receptors contribute to both exercise‐induced analgesia and exercise‐induced hyperalgesia in chronic pain conditions.
Effect of Inhaled Nitric Oxide on Exercise Capacity and Pulmonary Gas Exchange in Adult Survivors of Preterm Birth
Authors: Haraldsdottir Kristin , Farrell Emily , Bates Melissa , Pegelow David , Palta Mari , Goss Kara , Eldridge Marlowe
Published: November 2023

RATIONALE

Preterm birth affects millions of infants each year, and survival rates are on the rise. Frequently, premature birth results in alveolar simplification that may persist into adulthood. We have previously shown that pulmonary gas exchange efficiency is lower during exercise in some adults born preterm compared with control subjects. However, it is unknown whether the presence of inhaled nitric oxide (iNO), a potent broncho‐ and vasodilator, has an effect on pulmonary gas exchange and other physiological measures during exercise in preterm birth survivors. The objective of this study was to determine the effect of iNO on alveolar to arterial oxygen difference (AaO2), respiratory exchange ratio (RER), and maximum wattage during exercise in adult survivors of preterm birth.

METHODS

Fourteen young adults born preterm (recruited from the Newborn Lung Project, birth weight <1,500 g, gestational age <36wk, age 20–23 years) and 16 term‐born, age‐matched control subjects performed incremental exercise on a cycle ergometer to volitional exhaustion while breathing normoxic air with and without iNO. Arterial and venous blood samples were taken every two minutes. Ventilation, mixed expired gases, power output, and oxygen consumption were continuously measured during rest and exercise using LabChart. Max wattage, RER, and AaO2 were calculated. Statistics were done with two‐way ANOVA to compare control and preterm with and without iNO with Tukey's for multiple comparisons.

RESULTS

With respect to max power, controls attained a higher wattage than preterms in normoxia (p= 0.01). This difference was attenuated in the presence of iNO (174.3 ± 28.4 W controls without iNO v 141.4 ± 27.2 W preterms with iNO, p = 0.21). With respect to RER, there was no significant difference between controls and preterms in normoxia. In the presence of iNO, preterms had a significantly higher RER than controls without iNO throughout graded exercise (0.92 ± 0.10 v 0.89 ± 0.12, p = 0.0013). Preterms had a significantly higher AaO2 than controls during graded exercise in normoxia without iNO, which was attenuated with iNO (9.3 ±6.1 mmHg control v 11.6 ±10.8 mmHg preterm, p =0.21).

CONCLUSIONS

We have previously shown that pulmonary gas exchange efficiency is lower in some adult survivors of preterm birth during exercise compared with control subjects. Here we show that iNO in preterm adults attenuates many of the metabolic and pulmonary gas exchange differences between preterm and control adults during graded exercise, including AaO2 and max power. RER in the preterm + NO group was significantly higher than the controls without NO. Overall, this suggests iNO can improve gas exchange efficiency in preterm born young adults.

Support or Funding Information

NIH NHLBI, R01 HL086897 (Eldridge)

Nitric oxide was supplied by Mallinckrodt Pharmaceuticals, formerly Ikaria, Inc.
Effects of Voluntary Wheel Running During and Following Doxorubicin Treatment on Ex Vivo Skeletal Muscle Function
Authors: Hochberg Leanne M. , Borges Raquel L. , Hydock David S.
Published: November 2023

Doxorubicin (DOX), a widely used chemotherapeutic agent, manifests toxic side effects in healthy skeletal muscle cells. Existing studies describe attenuation of these myotoxic effects of DOX following exercise preconditioning regimens, but the effects of exercise during and following DOX treatment on myotoxicity are unidentified. Therefore, the objective of this study was to explore the effects of exercise during and following DOX treatment on skeletal muscle function. Male Sprague‐Dawley rats were randomly assigned to the exercise (voluntary wheel running) or sedentary (normal cages) condition for 10 weeks. Throughout this time, animals received DOX (2 mg/kg) or saline once a week for 6 weeks and continued the exercise or sedentary conditions for an additional 4 weeks. Soleus and extensor digitorum longus function was then measured ex vivo. Although DOX treatment impaired muscle function, voluntary wheel running during and following treatment mitigated this effect.
The Effects of Upper vs. Lower Body Fat and Aerobic Exercise on Indices of the Metabolic Syndrome
Authors: Apolzan John William , Talbert Willie M , Earnest Conrad P , Martin Corby K , Church Timothy S
Published: November 2023

Introduction

Apple shaped (higher waist to hip ratios; WHR) people have higher levels of abdominal and visceral adiposity and therefore higher risks of having type 2 diabetes and cardiovascular disease. Pear shaped (lower WHR) people have improved lipid homeostasis and insulin sensitivity compared to apple shaped people. Physical activity has been shown to improve indices of the metabolic syndrome. The purpose of this study was to examine the differential responses of indices of the metabolic syndrome to exercise in people with different body fat depots (i.e. apple vs. pear shapes).

Methods

The original study recruited healthy sedentary persons and randomized them to an aerobic exercise or control group. Data from female completers with pre and post CT scans were used in the analyses. Female participants were grouped based on the division of the WHR at the median. Thus, the present study had 4 groups.

Results

The study population (N=92) had an average age of 51±1 y and BMI of 31.4±0.4 kg/m2. The average WHR were: 0.88±0.04 exercise apple, 0.79±0.03 exercise pear, 089 ±0.04 control apple, and 0.79±0.04 control pear. Visceral adipose tissue decreased in both the apple and pear exercise groups (p=0.05). Apple exercisers tended to have greater reductions in blood pressure compared to the apple control group (p=0.06). Pear shaped individuals tended to have better circulating triglyceride levels (p=0.085) and VLDL levels (p=0.085) compared to apple exercise group. Body shape in aerobic exercisers tended to predict change in the following metabolic syndrome parameters: BMI (r=.25; p=0.08), hip circumference (r=.25; p=0.08), VLDL (r=.27; p=0.08), Cholesterol: HDL ratio (r=.25; p=0.06), and triglycerides (r=.27; p=0.06).

Conclusion

Apple and pear shaped participants decreased visceral adiposity with exercise. Persons with pear shapes should increase aerobic exercise to decrease circulating triglycerides and VLDL levels, while persons with apple shapes should increase aerobic exercise to decrease blood pressure. Aerobic exercise in pear shaped women predicted positive change in metabolic health outcomes.

Support or Funding Information

This research was funded by grants from the NIH including a T35 DK093428, U54 GM104940, and a HL 75442.
Do Compression Garments Improve Healing Among Runners With Acute Overuse Injuries of the Lower Extremities
Authors: Waller Lauren K , Donaldson Micheal , Giese Tera , Flaming Matt , Peterson Courtney , Raynes Edilberto
Published: November 2023

Over the past two decades, runners have received increased demands on their performance. This increase on physical demand has also caused an increase in the risk of acute superficial overuse sports injuries, with most running injuries being in the lower extremity. Consequently, the injuries cause inflammation and connective tissue damage. About 50 to 75% appear to be overuse injuries due to the constant repetition of the same movement. Recent studies have focused on the use of lower body compression garments as an aid in performance and recovery time. There is reason to believe that these garments have beneficial physical and physiological effects. The purpose of the research is to explore the advantages of wearing compression garments during and after training to help improve the healing and inflammatory processes. We hypothesize that wearing compression garments will increase blood flow to the damaged tissue area and will improve the healing process, thereby decreasing the recovery time.

Support or Funding Information

Dee U. Silverthorn, PhD, FAPS Professor of Physiology Dell Medical School | The University of Texas at Austino: 512‐495‐5098| silverthorn@utexas.edu| dellmedschool.utexas.edu1912 Speedway, Mail code D2000Sánchez Building (SZB), Suite 546.18 Austin, TX 78712
Effect of Deep Slow Breathing on Pain‐Related Variables in Osteoarthritis
Authors: Brilla Lorrie , Larsen K.L. , McLaughlin W.L. , Li Y.
Published: November 2023

This study evaluated the effect of a six‐week deep slow breathing (DSB) program on pain, physical function, and heart rate variability (HRV) in subjects with lower extremity joint pain. Twenty subjects were assigned into training (n=10) and control (n=10) groups. The training group participated in a six‐week DSB program consisting of weekly training sessions and at‐home breathing exercises. DSB exercises focused on prolonging the exhalation and the pause following exhalation. The Western Ontario and McMaster Osteoarthritis Index (WOMAC) was used to assess pain and physical function and HRV data were obtained pre‐ and post‐intervention. Results revealed no significant interactions between group and time for any of the variables. There was no significant main effect for group, but there was a significant main effect (p < 0.025) and a large effect size for time on both pain (training pre 148 ± 94, post 84 ± 89; control pre 123 ± 87, post 92 ± 73; group ηp2 = 0.003, time ηp2 = 0.454) and physical function (training pre 434 ± 268, post 276 ± 287; control pre 482 ± 346, post 338 ± 274; group ηp2 = 0.010, time ηp2 = 0.506). There were no significant main effects (p > 0.017) for group and time on LF power (training pre 179.30 ± 562.1 ms2, post 9.82 ± 28.84 ms2; control pre 32.08 ± 66.55 ms2, post 0.74 ± 0.73 ms2; group ηp2 = 0.039, time ηp2 = 0.061), HF power (training pre 14.04 ± 39.76 ms2, post 7.02 ± 19.24 ms2; control pre 7.43 ± 9.99 ms2, post 1.50 ± 1.87 ms2; group ηp2 = 0.039, time ηp2 = 0.039), and LF/HF ratio (training pre 5.64 ± 10.03, post 2.13 ± 3.72; control pre 2.38 ± 3.79, post 0.97 ± 0.69; group ηp2 = 0.036, time ηp2 = 0.169). Results indicated that the six‐week DSB program was not sufficient to improve pain or physical function in subjects with lower extremity joint pain. The significant improvements in pain and physical function from pre‐to post‐intervention for both groups may be the result of an increase in perceived social support during the study. As this is the first study to examine the use of DSB for lower extremity joint pain and dysfunction, further research is needed to investigate the efficacy and applicability of DSB.

Support or Funding Information

none
Effect of Leg Blood Flow Restriction during Cycling on Cerebral Perfusion: Role of Carbon Dioxide
Authors: Prodel Eliza , Balanos George M. , Braz Igor D. , Nobrega Antonio C. L. , Vianna Lauro C. , Fisher James P.
Published: November 2023

Exercise with blood flow restriction (BFR) enhances skeletal muscle metabolite accumulation and has been used to stimulate training‐induced improvements in strength and endurance, but the consequences for the cerebral circulation are unknown. The activation of group III and IV skeletal muscle afferents by exercise‐induced metabolites (muscle metaboreflex) has been suggested to increase cerebral perfusion during exercise. However, this may be masked by a hyperventilation related decrease in the partial pressure of arterial carbon dioxide (indexed by partial pressure of end‐tidal carbon dioxide; PETCO2). We sought to determine how muscle metaboreflex activation with BFR affects cerebral blood flow and whether this is secondary to confounding changes in PETCO2. In 11 healthy male participants (age 25±4 years; height 180±1 cm; weight 71±7 kg; mean±SD) we measured middle cerebral artery mean blood velocity (MCAVm), internal carotid artery blood flow (ICAQ) and PETCO2, during leg cycling exercise under free‐flow conditions (target heart rate at 120 bpm) and with BFR. Trials were conducted where PETCO2 was permitted to fluctuate spontaneously (control) and where PETCO2 was clamped at 1 mmHg above resting levels. In the control trial, PETCO2 was slightly increased from rest during leg cycling (Δ2.2±0.3 mmHg; P<0.05) and significantly decreased during exercise with BFR (Δ‐4.8±0.9 mmHg; P<0.05). PETCO2 remained unchanged throughout the clamp trial. Leg cycling under free‐flow conditions evoked similar increases in MCAVm during the control (Δ6.5±1.8 cm.s−1) and PETCO2 clamp (Δ6.8±2.4 cm.s−1) trials (P<0.05 vs. rest). During exercise with BFR a further increase in MCAVm was noted in the PETCO2 clamp trial (Δ5.9±1.4 cm.s−1; P<0.05 vs. rest and free‐flow exercise), but not in the control trial. In both trials, ICAQ was not significantly changed from rest during leg cycling under free‐flow conditions (control Δ‐3.5±10.31 ml.min−1; PETCO2 clamp Δ7.2±7.41 ml.min−1; P>0.05 vs. rest). During exercise with BFR, ICAQ was significantly increased when PETCO2 was clamped (Δ27.2±6.6 ml.min−1; P<0.05 vs. rest), but was decreased in the control trial (Δ‐22.7±12.1 ml.min−1; P<0.05 vs. rest). In conclusion, enhanced muscle metaboreflex activation with leg BFR during cycling increases cerebral blood flow, but only when PETCO2 is maintained at resting levels.

Support or Funding Information

This study was supported by Coordination for the Improvement of Higher Education Personnel (CAPES‐Brazil) through the program Science without Borders.
Effects of Ischemic Preconditioning on Neural and Hemodynamic Responses to Muscle Metaboreflex Activation
Authors: Incognito Anthony , Doherty Connor , Lee Jordan , Millar Philip
Published: November 2023

Ischemic preconditioning (IPC), the exposure to brief intermittent periods of circulatory occlusion, has been demonstrated to reduce submaximal lactate accumulation and improve exercise performance. Lactic acid is a potent stimulator of the muscle metaboreflex, which results in increased efferent sympathetic outflow to skeletal muscle. We tested the hypothesis that IPC would attenuate the neural (muscle sympathetic nerve activity (MSNA)) and hemodynamic response to activation of the muscle metaboreflex during post‐exercise circulatory occlusion (PECO). In a randomized‐controlled design, 17 healthy young (24±3 yrs), normotensive (107±7/64±5 mmHg) men were allocated to IPC (n=10) or sham‐IPC (n=7) treatment groups. IPC and sham‐IPC treatments consisted of 3 cycles of 5 min cuff inflation at 200 mmHg or 20 mmHg, respectively, each followed by a 5 min cuff deflation. Continuous measurements of MSNA (microneurography), blood pressure, heart rate, stroke volume, cardiac output and total peripheral resistance were collected at rest and during 2 min of isometric handgrip (IHG) at 30% of maximal voluntary contraction followed by 3 min of PECO, before and after an acute bout of IPC or sham‐IPC. Compared to baseline, MSNA burst frequency increased during IHG and PECO (both p<0.01) but was unchanged following IPC (IHG Δ9±10 vs. Δ10±7; PECO Δ7±11 vs. Δ8±7 bursts/min) or sham‐IPC (IHG: Δ5±2 vs. Δ5±3; PECO: Δ5±2 vs. Δ3±6 bursts/min). Systolic and diastolic blood pressure were increased during IHG and PECO (both p<0.01) but unchanged following IPC (IHG Δ23±13/17±9 vs. Δ21±10/16±7; PECO Δ19±14/11±7 vs. Δ18±15/11±8 mmHg) or sham‐IPC (IHG: Δ15±8/12±6 vs. Δ16±5/11±4; PECO Δ11±7/8±5 vs. Δ10±6/5±4 mmHg). Heart rate was increased during IHG (p<0.01) but not PECO and unchanged following IPC (IHG Δ18±11 vs. Δ19±12; PECO Δ5±7 vs. Δ6±8 bpm) or sham‐IPC (IHG: Δ15±9 vs. Δ13±8; PECO: Δ3±5 vs. Δ0±5 bursts/min). Similarly, stroke volume, cardiac output, and total peripheral resistance responses were unchanged by IPC or sham‐IPC (p>0.05). These findings suggest that IPC is not capable of modulating the efferent sympathetic or hemodynamic responses during exercise or muscle metaboreflex activation. The mechanisms responsible for improvements in exercise capacity and time‐trial performance following IPC require further investigation but are unlikely neurogenic.

Support or Funding Information

Canadian Institutes of Health Research (CIHR), National Science and Engineering Research Council (NSERC)
Sweating During Intermittent Exercise in the Heat in Young and Older Adults: A Role for P2 Receptors
Authors: Akbari Pegah , Fujii Naoto , Foudil‐bey Imane , Meade Robert D. , Singh Maya S. , Boulay Pierre , Sigal Ronald J. , Kenny Glen P.
Published: November 2023

Recent findings have identified nitric oxide synthase (NOS) as an important modulator of sweating during exercise. Additionally, in vitro studies have identified the presence of P2 receptors (a subgroup of purinergic receptors) on human eccrine sweat glands, which may indicate that these receptors can modulate sweating. If so, these receptors may influence sweating through NOS‐dependent mechanisms, given that P2 receptor activation can increase calcium ion concentration, which in turn can activate NOS. Studies also demonstrate that NOS‐dependent sweating is impaired in older adults during exercise in the heat. In parallel, P2 receptors are down regulated in older adults, suggesting the contribution of P2 receptors, if any, to sweating may also be impaired. Thus, we assessed the separate and combined contribution of NOS and P2 receptors to the sweating response during exercise in the heat. Additionally, we evaluated whether ageing influences these responses. Eight young (24±4 years) and nine older (57±6 years) adults performed an intermittent cycling protocol consisting of two 30 min bouts of exercise (Ex) at a fixed rate of heat production of 400 W in the heat (35°C); followed by 20 and 40 min of recovery respectively. Sweat rate (ventilated capsule) was monitored at four forearm skin sites continuously perfused via intradermal microdialysis: 1) lactated Ringer (Control), 2) 10 mM NG‐nitro‐L‐arginine methyl ester (L‐NAME, a non‐selective NOS inhibitor), 3) 100 mM pyridoxine (PDX, non‐selective P2 receptor blocker), or 4) a combination of PDX and L‐NAME. We show that in young adults, administration of L‐NAME attenuated sweat rate (Ex1: 0.65 mg min−1cm−2; Ex2: 0.67 mg min−1cm−2) in comparison to Control (Ex1: 0.79 mg min−1cm−2; Ex2: 0.82 mg min−1cm−2) at the end of both exercise bouts (both P≤0.05). Further, infusion of PDX, both independently (Ex1: 0.69 mg min−1cm−2, P=0.07; Ex2: 0.73 mg min−1cm−2, P=0.04) and in combination with L‐NAME (Ex1: 0.69 mg min−1cm−2, P=0.04; Ex2: 0.74 mg min−1cm−2, P=0.09), tended to reduce sweat rate relative to Control; albeit, these responses were not all statistically significant. However, the magnitude of reduction at each site compared to Control were not different (P=0.32). Finally, no differences in local sweat rate were observed between treatment sites in older adults (P=0.20). In summary, our findings indicate that P2 receptor activation can contribute to sweating in young adults through a NOS‐dependent mechanism. However, the contribution of these pathways to the sweating response is diminished in older adults.

Support or Funding Information

Funding support: This study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).
Influence of Time of Day on Post‐Exercise Hypotension Might Be Different in Hypertensives Receiving Different Anti‐hypertensive Drugs: An Exploratory Study
Authors: Brito Leandro , Peçanha Tiago , Fecchio Rafael , Sousa Patricia , Rezende Rafael , Navarro Marilia , Silva Giovânio , Abreu Andrea , Mion‐Junior Décio , Forjaz Claudia
Published: November 2023

Introduction

In a previous study, we observed that time of day can affect post‐exercise hypotension (PEH) in none medicated pre‐hypertensives. PEH is greater in hypertensives, and different classes of anti‐hypertensive drugs might interact with time of day to affect PEH, but this has not been investigated.

Objective

To compare PEH after maximal exercise performed in the morning and evening in hypertensives taking angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs).

Methods

Sixteen hypertensive men were allocated into two groups according to type of anti‐hypertensive drug (ACEi, n=8 and ARBs, n=8). All subjects underwent, in a random order, two maximal exercise tests (cycle ergometer, 15 watts/min until exhaustion followed by 5 min of recovery at 30 W): one conducted in the morning, between 7 and 9 a.m., and another in the evening, between 8 and 10 p.m. Systolic and diastolic blood pressures (BP) were assessed before and 30 min after the maximal tests. A 3‐way ANOVA for repeated measures was employed, considering the main factors: group (ACEi vs ARBs), time of day (morning vs evening) and condition (pre vs post‐exercise).

Results

Systolic BP decrease was not different after exercise conducted in morning and evening for the ACEi group (−7±6 vs −6±8 mmHg, p=0.72), but for the ARBs group, systolic BP decrease was greater in the evening compared to the morning (−7±7 vs −13±9 mmHg, p<0.01) and also compared to the ACEi group (−13±9 vs. −6±8 mmHg, p=0.01). Diastolic BP did not change after exercise in either groups at either time of day.

Conclusion

This exploratory study showed that systolic PEH is greater after evening than morning exercise in hypertensive patients receiving ARBs but not ACEi. Thus, ARBs associated with aerobic exercise might promote a greater PEH in the evening.

Support or Funding Information

Financial support: FAPESP: 2014/21667‐6.