bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of changes in the immune system in rats exposed to different doses of lithium for a long‐term period (876.4)
Authors: Matur Erdal , Darıyerli Nuran , Akyol Sibel , Toplan Selmin , Özdemir Semra
Published: June 2021

The effects of lithium which is widely used for the treatment of bipolar disorder, on the specific and non‐specific immune systems of rats have been investigated. Forty male rats were used. The rats were divided into control and four treatment groups, each contained 8 animals. While control group were fed with standard commercial pellet, 1, 1.4, 1.8 and 2.2 g/kg lithium was added to the diets of group‐I, II, III and IV respectively for 30‐days.

Liver, spleen and kidney and body weight were weighed. Total white blood cell, granulocyte, lymphocyte and monocyte percentage, CD3, CD4, CD8, CD161 cells, CD4/CD8 ratio and serum lithium level were determined.

The body weight decreased depending on the dose of the lithium. Treatments did not affect the relative weight of the organs studied. Granulocyte percentage was increased (P=0.026) significantly related to lithium dose. CD3 and CD4 cell ratios significantly decreased (P= 0.004 and P= 0.005 respectively) in rats fed with 2.2 g/kg lithium added diet. Despite of a numerical decrease in CD4 cells in group which were given 1.8 mg/kg lithium, this decrease was not statistically significant. There was no significant change in rates of CD8, CD161 cells in peripheral blood. On the other hand the rate of CD4/CD8 cells in groups given lithium 1.8g/kg and 2.2g/kg dosages were found to be significantly low when compared with the control and the other groups.

It is concluded that lithium therapy may activate the non‐specific immune system by increasing the granulocytes percentage, but it has negative influences on the body weight, cells of CD3, CD4 and CD4/CD8 rate which are the key cells of the specific immune system.

Grant Funding Source: This work was supported by the Research Fund of Istanbul University
Identification of corticotropin‐releasing hormone neurons in paraventricular nucleus in rats (876.6)
Authors: Li De‐Pei
Published: June 2021

Corticotropin‐releasing factor (CRH) neurons in the paraventricular nucleus (PVN) are the essential component of the hypothalamus‐pituitary‐adrenal axis play a critical role in the regulation of autonomic, endocrine and behavioral responses to stress. Assessment of the CRH neurons provides valuable information on cellular mechanisms during physiological and disease process. However, CRH neurons in the rats cannot be reliably identified in live tissues since the identification of CRH neurons requires neuronal labeling and post‐mortem immunohistochemistry. To efficiently identifying CRH neurons in live tissue, we constructed a CRH promoter‐GFP plasmid and integrated this sequence into an adeno‐associated virus (AAV) vector. This AAV‐CRH promoter‐GFP vector was delivered into the rat PVN through microinjection (100 nl). The hypothalamic slices containing GFP‐tagged neurons was immunostained with a specific antibody against CRH. We found that 76.4% CRH immunoreactivity positive PVN neurons colocalized with GFP and 92.8% GFP‐tagged PVN neurons expressed CRH immunoreactivity. Whole‐cell recordings were performed on these GFP‐tagged CRH neurons in hypothalamic slice to assess their electrophysiological properties. Therefore, this AAV‐CRH‐GFP reliably targets CRH neurons in rat brain for in vitro assessment.

Grant Funding Source: NIH: MH096086
Pharmacological hypothermia by Trpv1 agonism provides neuroprotection following ischemic stroke (877.13)
Authors: Cao Zhijuan , Balasubramanian Adithya , Marrelli Sean
Published: June 2021

Stroke is the leading cause of death and major cause of long‐term disability. Current therapeutic hypothermia by physical cooling shows the potential for neuroprotection in animal ischemic stroke, but causes complications and often requires sedation and muscle paralysis. The limitations restrict the translational application in clinic. Our previous studies show agonism of transient receptor potential vanilloid 1 (TRPV1) by dihydrocapsaicin (DHC) induces reliable and reversible pharmacological hypothermia (PH). We hypothesize that DHC induced hypothermia provides neuroprotection in ischemic stroke mice.

Acute response of HR, BP and cerebral perfusion to the therapeutic dose of DHC were measured. C57BL/6 WT and TRPV1 KO mice were treated with therapeutic doses (1.25, 1.25 mg/kg) and high doses (30, 15 mg/kg) at two consecutive days. After one month recovery, the temperature change response of DHC (1.25 mg/kg) was applied to evaluate the potential TRPV1 desensitization. Focal cerebral I/R (one hour ischemia + 24 hours reperfusion) was induced by distal middle cerebral artery plus common carotid artery transient occlusion in conscious WT and TRPV1 KO mice. PH (8 hours) was initiated 90 minutes after start of reperfusion by DHC infusion (osmotic pump). Neurofunction (by behavioral tests) and infarct volume (by TTC staining) were measured at 24 hours.

DHC (1.25 mg/kg) had no measurable effect on HR and cerebral perfusion, did not desensitize TRPV1 channels, but produced a slight transient drop in BP (<6mmHg). In I/R mice, DHC infusion produced mild hypothermia, decreased infarct volume by 87%, and improved neurofunctional score. The hypothermic and neuroprotective effects were absent in TRPV1 KO mice or mice maintained normothermic with heat support.

TRPV1 agonism provides an effective and well‐tolerated PH for acute cerebral I/R neuroprotection. Hypothermic and neuroprotective effects are specifically through TRPV1 agonism.

Grant Funding Source: Supported by NIH R21 NS077413, R01 HL088435 (SPM) and AHA Pre Doctoral fellowship 16900006 (ZJC).
Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia‐ischemia (877.2)
Authors: Kajimura Mayumi , Takenouchi Toshiki , Nakanishi Tsuyoshi , Sugiura Yuki , Hishiki Takako , Suematsu Makoto
Published: June 2021

Although therapeutic hypothermia has been shown to improve neurologic outcomes after the perinatal cerebral hypoxia‐ischemia, etiology remains unknown. To decipher mechanisms whereby hypothermia regulates metabolism in different regions of the brain, we took a two‐step approach; metabolomics to target metabolic pathways responding to lowering temperature, and quantitative imaging mass spectrometry (Q‐IMS) to reveal spatial alterations in targeted metabolites at specific regions of the brain. 7‐day postnatal rats underwent permanent ligation of left common carotid artery followed by exposure to 8% O2 for 2.5 hrs. Pups were returned to normoxia at either 38 °C or 30 °C for 3 hrs. Brain metabolism was rapidly fixed by in‐situ freezing. Profiling of 107metabolites showed that hypothermia diminishes the carbon biomass related to acetyl‐moieties such as pyruvate and acetyl CoA; conversely, it increases deacetylated metabolites such as carnitine and choline. Q‐IMS indicated that hypothermia diminishes ACh contents specifically in hippocampus and amygdala. The decrease is associated with an inverse increase in carnitine in the same anatomical regions. These findings imply that therapeutic hypothermia achieves neuroprotective effects by mediating acetylation status with coordinated suppression of acetyl CoA which resides in metabolic crossroads of glycolysis, amino acid catabolism and ketolysis.

Grant Funding Source: Grant‐in‐Aid for Scientific Research 24791121 and 24500448 from the Japan Society for the Promotion
Pinocembrin protects against beta‐amyloid‐induced toxicity in neurons through inhibiting RAGE‐independent signaling pathways and regulating mitochondrion‐mediated apoptosis (877.4)
Authors: Liu Rui , Zhou Dan , Zhang Li , Zhang Li , Zhang Tian‐tai , Du Guan‐hua
Published: June 2021

Amyloid‐β (Aβ) peptides accumulate in the brain and initiate a cascade of pathological events in Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE) has been implicated to mediate Aβ‐induced perturbations in AD. Pinocembrin was approved by the SFDA of China for clinical use for stroke patients and evidenced with neuroprotection against Aβ‐induced toxicity, but the therapeutic role and mechanism are not ascertained. Here, we report that pinocembrin improves cognition and protects neuron against Aβ‐mediated toxicity. Oral treatment of pinocembrin for 8 days improved cognitive function, preserved ultrastructural neuropils and decreased neurodegeneration in Aβ‐treated mice. Pinocembrin did not provide sufficient effect on inhibiting Aβ production. However, it inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and then, markedly depressed the activation of MAPK pathways and the downstream NF‐κB inflammatory response subsequent to Aβ‐RAGE interaction. In addition, pinocembrin alleviated mitochondrial dysfunction, and regulated mitochondrion‐mediated apoptosis. In conclusion, pinocembrin showed cognitive improvement and neuronal protection in AD models. The mechanisms were illustrated on RAGE‐dependent transduction inhibition and mitochondrion protection. It appears to be a promising candidate for the prevention and therapy of AD.

Grant Funding Source: National Natural Science Foundation of China (No. 81102830)
Post‐TBI administration of DHA selectively suppresses pro‐inflammatory and promotes resolving microglial activation (877.5)
Authors: Harvey Lloyd , Begum Gulnaz , Dixon C. , Sun Dandan
Published: June 2021

We investigated the manifestation of neuroinflammation after traumatic brain injury (TBI) and the efficacy of docosahexaenoic acid (DHA) in reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered interperitonially at 5 min after TBI, followed by a daily dose for 3‐21 days. TBI triggered activation of microglia, detected by increase of Iba1 positively stained microglial cells in cortical tissues at 3‐21 days post‐TBI. The neuroinflammatory response was further characterized by an increased expression of the pro‐inflammatory marker CD16/32 in Iba1+ microglia at 3‐7 days post‐TBI. The Iba1+ microglia surrounded cortical neurons exhibiting ER stress. In contrast, DHA reduced acute neuronal damage and ER stress at 3 days post‐TBI. DHA‐treated TBI brains also showed significantly less CD16/32+ and Iba1+ microglial population, but increased CD206+/Iba1+ microglial (phagocytic) population. In summary, this study demonstrated that TBI induces a profound neuroinflammatory response that is characterized by pro‐inflammatory microglial activation. ER stress‐associated inflammation may play a role in the activation of microglia. Post‐TBI administration of DHA reduces neuronal damage, ER stress, and promotes the resolving microglial activation.

Grant Funding Source: Supported by Univ. of Pitt. startup funds, endowed Chair Professorship (DS) & VA RR&D grant (CED).
Crude oil impairs cardiac excitation‐contraction coupling in fish (878.3)
Authors: Block Barbara , Brette Fabien , Cros Caroline , Incardona John , Scholz Nathaniel
Published: June 2021

New research from oil spills (Deepwater Horizon, Gulf of Mexico) indicates that crude oil is a toxicant that produces cardiac defects. The developing fish heart is a sensitive target organ for the toxic effects of crude oil‐derived polycyclic aromatic hydrocarbons (PAHs). Specific cardiotoxicity phenotypes have been identified in which cardiac excitability, contractility and morphology are impacted. Little is known about the toxic effects of crude oil upon cardiac function in vertebrates. We isolated myocytes from the hearts of fish and show that 4 types of crude oils collected during the Deepwater Horizon oil spill prolonged myocyte action potential duration. This prolongation is due to a block of K+ channel current, homologous to the hERG channel in human. In addition, crude oil exposure decreases Ca2+ current and Ca2+ cycling in isolated myocytes. These results indicate that excitation‐contraction coupling in fish is disrupted by low concentrations of crude oil. Our findings confirm a cardiotoxic mechanism for crude oil and reveal a potential for life threatening cardiac arrhythmias in vertebrates.

Grant Funding Source: NOAA
Arterial chemoreception in Tupinambis merianae: evidence for carotid body homolog in lizards (879.12)
Authors: Reichert Michelle , Milsom William
Published: June 2021

Observational studies and evolutionary history provide indirect evidence for the existence of a chemoreceptor population at the first major bifurcation of the common carotid artery in lizards, but a chemoreceptive role for this area has not yet been demonstrated. We explored this possibility by measuring cardiorespiratory variables in response to arterial injections of the hypoxia mimic sodium cyanide (NaCN) into the carotid artery of 12 unanesthetized specimens of Tupinambis merianae. These injections elicited increases in heart rate (fH; 101±35% increase) and respiratory rate (fR; 620±119% increase), but not mean arterial blood pressure (MAP). These responses were eliminated by vagal denervation. Similar responses were elicited by injections of the neurotransmitters acetylcholine (ACh) and serotonin (5HT) but not norepinephrine. Heart rate and respiratory rate increases in response to NaCN could be blocked or reduced by either the antagonist to ACh (atropine) and/or 5‐HT (methysergide). Finally, using immunohistochemistry we demonstrated the presence of glomus‐like cells containing either ACh or 5‐HT (but not both) in the vessel walls of the carotid bifurcation. These results provide compelling evidence for the existence of carotid artery chemoreceptors in lizards at the site of the first carotid bifurcation just outside the heart with similar properties to known carotid body homologs.
Using PU4ii corrosion casts to characterize the tracheal system of the grasshopper leg (879.21)
Authors: Ferrara Nicholas , Lew James , Kirkton Scott
Published: June 2021

The lightweight, air‐filled tracheal system has enabled insects to be the most evolutionary successful animals on the planet. While adult Schistocerca americana grasshoppers use abdominal pumping and convection to drive oxygen through their head, thorax, and abdomen, it is less clear how oxygen delivery occurs down the metathoracic jumping leg. We cannulated the tracheal system of an adult grasshopper and injected PU4ii [vasQtec, Switzerland] low viscosity polymer resin, to create a corrosion cast of the tracheal system of the metathoracic leg. After the resin had solidified, tissues were chemically digested, leaving only the tracheal cast. The cast revealed a highly organized system. In the femur, six primary tracheae [0.2‐0.3 mm diameter] run along the proximodistal axis, connected via more than 20 secondary tracheae [0.09‐0.2 mm] running along the dorsoventral axis in a chevron pattern. Secondary tracheae form a network around the femur between the dorsal and ventral primary tracheae on each face. Many tertiary tracheae [9‐25 µm] descend from the chevrons into the muscle cavity. The lateral face of the femur has an additional central primary tracheae and 40° angled chevrons, while the medial face has only dorsal and ventral primary tracheae and 130° angled chevrons. Air sacs have been observed in multiple locations down the leg: at the junction between the primary and secondary tracheae, in the hip and knee joints, and in the tibial spikes. Results indicate PU4ii resin yields higher resolution casts than alternative methods using Mercox resin.

Grant Funding Source: Supported by Union College Undergraduate Research Grants
Blood flow distribution following adrenergic blockade and nitric oxide production inhibition in embryonic American alligators, Alligator mississippiensis (879.4)
Authors: Kohl Zachary , Tate Kevin , Elsey Ruth , Crossley Dane
Published: June 2021

Assessment of cardiovascular function in developing egg‐laying amniotes has been primarily limited to measurements made via catheters in the chorioallantoic membrane (CAM) and potentially invasive femoral and major outflow tract flow probes. Here we assess the capacity of embryonic alligators, Alligator mississippiensis, to regulate blood flow distribution using a minimally invasive microsphere distribution technique at 70 and 90% of development, in eggs incubated in normoxia or 10% hypoxia. Measurements were made in normoxia, acute 10% hypoxia, and acute 10% hypoxia following nitric oxide inhibition or alpha‐receptor blockade. We hypothesized that the embryonic response is concomitant with a redistribution of blood flow to the brain, heart, and CAM vasculature. Embryonic alligators respond to hypoxia with an initial bradycardia followed by a hypertensive tachycardia, however chronic hypoxic incubation blunts this response. Our data suggest that cardiac output is reduced during acute hypoxia in normoxic‐incubated embryos while it is maintained the hypoxic group. In addition, tonic nitric oxide dilation is present at 70% of incubation however inhibition of this tone does not modify total cardiac output at 90% of incubation. Our data suggest that hypoxic development may modify the patterns of blood flow redistribution in embryonic alligators and the mechanisms used to achieve this.

Grant Funding Source: NSF CAREER IBN IOS‐0845741 to DAC
Understanding how honey bee flight and senescence are connected through oxidative stress (880.1)
Authors: Margotta Joseph , Elekonich Michelle , Roberts Stephen
Published: June 2021

Honey bee age, behavior, functional senescence, and lifespan are easily manipulated independently of each other while in its natural environment and flying honey bees have the highest mass specific metabolic rate measured to date making the honey bee the ideal system to test the connection between oxidative stress and behaviors with a high aerobic expenditure. The main objectives of this work were to (a) determine if there is a cause‐effect relationship between honey bee flight and oxidative stress by comparing damage accrued from intense flight bouts to damage accrued from galactose treatment, which is a known proxy of oxidative stress in other insects, and (b) experimentally manipulate the duration and intensity of honey bee flight along with age to determine their effects on ROS accumulation and the associated enzymatic antioxidant protective mechanisms. Levels of 8‐hydroxy‐deoxyguanosine, a marker of DNA damage were increased in flying bees with high amounts of flight experience. We also saw an imbalance between pro‐oxidants and anti‐oxidants in bees with high amounts of flight experience. These data suggest flight‐induced oxidative stress plays a significant role in functional senescence of foraging honey bees that spend most of each day on the wing. Additionally, these data suggest that highly metabolic behaviors may contribute to oxidative stress and senescence of highly‐metabolic organisms.
Exercise protects against reperfusion arrhythmia by sustaining mitochondrial energetics (881.1)
Authors: Alleman Rick , Patel Hetal , Moukdar Fatiha , Brown David
Published: June 2021

Exercise is known to confer cardioprotection against ventricular arrhythmia and reduce the incidence of sudden cardiac death, yet the underlying mechanisms are not fully understood. We have previously shown that the transition to arrhythmia occurs concomitant with a collapse in mitochondrial energetics, which induces action potential lability via ATP‐ and redox‐sensitive ion channels. In this study, we hypothesized that the cardioprotection observed in exercised (Ex; 10 d of treadmill running) animals would be associated with maintenance of mitochondrial membrane potential (ΔΨm) in early reperfusion. We used a novel combination of two‐photon microscopy in intact, perfused hearts, coupled to simultaneous electrocardiogram recording to test our hypothesis. Hearts underwent 40/30 min of ischemia/reperfusion. Consistent with our previous work, hearts that displayed heterogeneous collapses in ΔΨm transitioned to ventricular arrhythmia. Hearts from Ex animals experienced a much lower incidence of reperfusion arrhythmia than sedentary counterparts, with 7 of 8 Sed hearts experiencing tachycardia or fibrillation compared to 3 of 8 Ex hearts. ΔΨm, assessed with the fluorescent probe TMRM, was better maintained in Ex hearts during the first 10 minutes of reperfusion. Mitochondrial respiratory control ratios were similar following ischemia/reperfusion in Sed and Ex (9.00±0.92 v. 9.03±0.70, respectively), suggesting that mitochondrial damage was similar across groups. These data provide a definitive link between sustaining mitochondrial energetics and prevention of electrical dysfunction with Ex, and suggest that therapies that preserve ΔΨm can mitigate sudden cardiac death in patients experiencing acute coronary syndromes.
The effects of moderate intensity exercise training on the incidence of supraventricular arrhythmias and atrial connexin40 and connexin43 expression in young and aged rats (881.3)
Authors: Kadow Zachary , Jepson Amanda , Firkins Rachel , Davenport Ashley , Henry Matthew , Moffitt Julia
Published: June 2021

Supraventricular arrhythmias are the most prevalent of all arrhythmias, with the elderly being at the greatest risk. Exercise training has been repeatedly shown to reduce supraventricular arrhythmic susceptibility. Connexin 40 (Cx40) is known to be the primary regulator of conduction between atrial cardiomyocytes and alteration of its expression has been associated with atrial arrhythmia development. Recent evidence also suggests that Connexin 43 (Cx43) assists in controlling atrial electrical conduction. We hypothesized that exercise training would reduce atrial arrhythmic susceptibility in young and aged animals and would be accompanied by changes in atrial Cx40 and Cx43 expression and/or phosphorylation. Groups of young and aged F344 rats underwent treadmill exercise training or sedentary handling. Subcutaneous electrocardiographic leads were then implanted following the respective exercise or sedentary protocols. The arrhythmic index (AI) was calculated using a modified scoring system totaling supraventricular arrhythmias during a baseline period (BL), sympathoexcitation (isoproterenol, 150 mg/kg s.c), and psychological stressor (BR). AI was significantly reduced during BL and ISO periods in young exercise animals compared to sedentary counterparts. Western blot analysis showed significantly greater atrial Cx43 expression in aged exercise compared to aged sedentary rats, while there was no significant change in the young animals. Preliminary evidence suggests an opposite pattern observed in atrial Cx40 expression, trending towards increased expression in young exercise compared to young sedentary rats, while showing no changes in aged animals. These preliminary results indicate moderate exercise training may be cardioprotective in a young animal model by reducing supraventricular arrhythmias and increasing atrial Cx40 expression while a similar aged model increases atrial Cx43 expression.
Exercise training induced bradycardia: evidence for enhanced parasympathetic regulation without changes in “intrinsic” sino‐atrial node function (881.5)
Authors: Billman George , Cagnoli Kristen , Fedorov Vadim
Published: June 2021

Although bradycardia is a well‐established consequence of endurance exercise training, the mechanisms responsible for this reduction in baseline heart rate (HR) remain controversial. Therefore, changes in cardiac autonomic regulation and intrinsic sino‐atrial nodal (SAN) rate were evaluated using mixed‐breed dogs randomly assigned to either a 10‐wk exercise training (ET, n = 15) or an equivalent sedentary period (SP, n = 10). Intrinsic HR was revealed by combined autonomic neural blockade (propranolol HCl, 1.0 mg/kg + atropine sulfate, 50 ug/kg, i.v.) before and after completion of the 10‐wk study. At the end of the study, SAN function was further evaluated by examining the SAN recovery time (SNRT) following rapid atrial pacing (1 min at 3.3 ‐ 10Hz). As expected, baseline HR decreased and heart rate variability [HRV, indices of cardiac vagal tone ‐ as measured by the high frequency component of R‐R variability (HF) and R‐R interval standard deviation (SD)] increased in the ET (HR pre 113.4 ± 3.9, post 105.2 ± 3.9 beats/min; HF pre 7.0 ± 0.2, post 8.2 ± 0.2 ln ms2; SD pre 57.8 ± 100.5 ± 9.2 ms) but not in the SP group (HR pre 113.0 ± 10.3, post 122.4 ± 5.4 beats/min; HF pre 7.4 ± 0.5, post 7.0 ± 0.6 ln ms2; SD pre 62.2 ± 9.9, post 63.6 ± 7.3 ms). Atropine induced significantly (ANOVA, P <0.01) greater reductions in HRV in the ET (HF pre ‐6.9 ± 0.3. post ‐7.6 ln ms2; SD, pre ‐50.0 ± 3.7, post ‐90.6 ± 9.7 ms) as compared to the SP (HF ‐7.1 ± 0.5, post ‐6.6 ± 0.5 ln ms2; SD pre ‐66.0 ± 11.3, post ‐59.2 ± 6.8 ms) group. In contrast, neither intrinsic HR (e.g., ET pre 141.2 ± 6.7, post 146.0 ± 8.0; SP pre 149.8 ± 8.9, Post 150.0 ± 12.6 beats/min) nor SNRT (HR corrected) differed in the ET and SP groups. These data suggest that endurance exercise training induced changes in baseline HR result from an enhanced cardiac parasympathetic regulation and not from changes in the intrinsic function of the sino‐atrial node.
Low intensity resistance training promotes peripheral and central adjusts on cardiovascular control (881.6)
Authors: Oliveira Larissa , Macedo Fabricio , de Melo Vitor , Mota Marcelo , da Silva Tharciano Luiz , Fontes Milene , Santana Michael Nadson , dos Santos Robervan , Barreto Andre , dos Santos Márcio Roberto , Santana‐Filho Valter
Published: June 2021

The aim was to evaluate the effects of low intensity resistance training (RT) on blood pressure, cardiovascular autonomic balance and vascular reactivity. One group of animals were submitted to RT. Control animals (CO) were fictitious trained (no exercise). After 8 weeks of RT or fictitious exercise, blood pressure and pulse interval were recorded and mesenteric artery was removed and sliced in rings for vascular reactivity analysis (Acetilcholine (ACh): 10‐9 ‐ 10‐4 M; Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME): 100µM). The variabilities of pulse interval, blood pressure and spontaneous baroreflex sensitivity (BRS) were analyzed. RT animals showed a reduction in mean arterial pressure (CO 117.04 ± 2.68 vs RT 105.5 ± 4.28), diastolic arterial pressure (CO 107.71 ± 2.95 vs RT 97 ± 3.42) and heart rate (CO 395 ± 7.1 vs RT 344 ± 13.25). In addition, it was seen in trained animals an increase in cardiac vagal modulation (LF/HF: CO 0.35 ± 0.08 vs RT 0.14 ± 0.03), BRS (CO 0.77 ± 0.01 vs RT 1.05 ± 0.1) and percentage of ACh‐induced relaxation of mesenteric arterial rings (pD2: CO 6.2 ± 0.1 vs RT 7.1 ± 0.1) and addition of L‐NAME reduced the ACh‐induced relaxation (CO 52.0 ± 3.2% vs RT 35.8 ± 3.7%). In conclusion, we observed that low intensity RT was able to promote beneficial cardiovascular adaptations mediated by central and peripheral adjustments.

Grant Funding Source: Supported by CNPq Foundation (Brazil)
Effect of sudarshankriya yoga on cardiac autonomic and pulmonary functions (881.9)
Authors: Dhawan Ashwani , Peter Rosemarry , Goel Rakesh
Published: June 2021

Yogic breathing techniques are often recommended for relaxation and stress management, This has been claimed to have effect over autonomic nervous system imbalances and psychological or stress‐related disorders. Sudarshan kriya yoga (SKY) is a type of cyclical controlled breathing practice which has roots in traditional yoga and it is taught by the nonprofit organization Art of Living Foundation India. Sudarshan Kriya. which is an advanced form of rhythmic, cyclical breathing with slow, medium, and fast cycles. The objective of this study is to observe the effect of Sudarshan Kriya Yoga on cardiac autonomic and respiratory functions. SKY program was introduced to the participants through a course of 6 days. It was an interactive session in which SKY, a rhythmic cyclical breathing was taught to 50 subjects of age 20‐50 years of both sexes by a certified teacher from Art of Living foundation. Cardiac autonomic and pulmonary function tests were done before the beginning and after one month of intervention of SKY. In this protocol all participants practiced SKY for 45 minutes each session minimum 4 days in a week for one month. Improvement in all parameters were observed after practicing Sudarshan Kriya Yoga for one month. Heart rate and Blood pressure decreased p>.05. An increase in HF and decrease in LF/HF ratio were observed. FVC, FEV1, PEFR and FEV1/FVC were improved p>.05. Though the improvement is statistically not significant with one month time period, long term intervention seems to be promising.

Grant Funding Source: Maharaja Agarsen Medical College Agroha Hisar India
Deployment length and its correlation with spirometric variables in deployed veterans (882.1)
Authors: Chen Yang , Klein Jacquelyn , Ndirangu Duncan , Smith Webb , Falvo Michael
Published: June 2021

Military personnel deployed to Iraq and Afghanistan are likely to have been exposed to high levels of air pollution during their deployment and frequently report respiratory symptoms post‐deployment. The goal of this study was to determine whether deployment length is associated with lung function. We recruited 36 veterans (40±9.9 yrs) deployed to Iraq and Afghanistan to participate in this study. Veterans completed deployment history questionnaires and performed forced expiratory maneuvers in accordance with ATS/ERS task force guidelines. Spirograms were analyzed for the following variables: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), the ratio of FEV1/FVC, the ratio of FEV3/FVC and midexpiratory flow (FEF25‐75). Percent predicted (%pred) values were then calculated based on NHANES III reference equations. We found deployment length was significantly correlated to FEV1%pred (r=‐0.39, p=0.018), FEV1/FVC%pred (r=‐0.38, p=0.021), FEV3/FVC%pred (r=‐0.439, p=0.009), FEF25‐75%pred (r=‐0.377, p=0.023), but not FVC (r=‐0.03, p=0.863). In this preliminary evaluation, we observed an inverse relationship between deployment length and several spirometric variables. Future studies in larger cohorts are necessary to confirm these findings and better understand the relationship between deployment‐related exposures and lung function. Work supported by VA Grants.

Grant Funding Source: VA Grants 1I21RX001079‐01 and 1I21CX000797‐01
Acute passive stretching alters ventilatory pattern during prolonged cycle exercise (882.2)
Authors: Esposito Fabio , Limonta Eloisa , Cè Emiliano , Rampichini Susanna , Riboli Andrea , Veicsteinas Arsenio
Published: June 2021

Passive stretching may induce the activation of receptors on the terminal end of group III and IV nerve fibers located within joints and muscles through mechanical and chemical stimuli. The aim of the study was to assess the effects of an acute bout of passive stretching on the ventilatory pattern during exercise. Maximum oxygen uptake (VO2max) was determined in nine participants who then performed a sustained cycle exercise of high intensity (85% of VO2max, W85) up to exhaustion, with and without previous stretching administration (on different days, in random order). During the tests metabolic and respiratory parameters were recorded breath‐by‐breath. Time to exhaustion in the W85 test was significantly shorter (−29%) with stretching. During the first 12 minutes of exercise the following parameters were significantly higher with stretching than without: VO2 (+4%), VE (+9%), respiratory muscle power (+16%) and respiratory muscle VO2 (+13%). The increase in VE was accompanied mainly by an increase in respiratory frequency rather than in tidal volume. Stretching altered the respiratory and metabolic response to exercise Whether the higher VE during exercise after stretching is a consequence of higher muscle afferent activation or higher metabolic rate, though, requires further investigation., but its effects on VE need further investigation.
Lunar and Mars simulated extravehicular activity evoked physiological responses (882.7)
Authors: Broxterman Ryan , Ade Carl , Wilcox Samuel , Craig Jesse , Barstow Thomas
Published: June 2021

It is currently unclear what physiological measurements from astronauts performing EVAs best indicate impending task failure. To date 7 subjects have completed a treadmill test for determination of maximal O2 uptake (V̇O2max) and two simulated EVAs at governed paces to evoke Lunar (V̇O2 ~20 ml/kg/min) and Mars (V̇O2 ~30 ml/kg/min) intensities, which have previously been reported for these environments. Subjects were separated into two groups based upon completion (COM) or failure (FAIL) of the Mars EVA. There were no significant (p > 0.05) differences between V̇O2 (Lunar COM 19.6 ± 1.3 ml/kg/min vs. FAIL 20.2 ± 0.9 ml/kg/min; Mars COM 29.9 ± 2.4 ml/kg/min vs. FAIL 30.0 ± 1.8 ml/kg/min), while FAIL %V̇O2max was significantly (p < 0.05) higher (Lunar COM 42.1 ± 3.9 % vs. FAIL 55.9 ± 1.3%; Mars COM 64.5 ± 8.5% vs. FAIL 83.1 ± 7.1%). FAIL V̇O2 rose throughout the Mars EVA until failure, while steady‐states were achieved in both groups for all other EVAs. Vastus lateralis muscle oxygenation and electromyographic data were not significantly (p > 0.05) different. These results indicate that global systemic measurements of EVA intensity are more informative of impending EVA failure than peripheral. The V̇O2 responses are characteristic of activities performed above & below critical power/speed. Thus critical speed may be vital to know for an astronaut prior to and during a mission, as EVA intensities above these will lead to task failure.

Grant Funding Source: Supported by NASA Grant NNX10AK60G
Physical exercise benefits on insulin sensitivity, vascular function and non‐alcoholic fat liver disease in cafeteria diet‐fed rats (884.11)
Authors: de Moraes Camila , Oharomari Leandro , Joaquim Anderson , Garcia Nádia , Ovidio Paula , Jordão Junior Alceu
Published: June 2021

Excessive consumption of high fat and refined sugar diet leads to metabolic disorders as obesity and its comorbidities. The effects of physical exercise on metabolic, hepatic and vascular function were evaluated in cafeteria diet‐fed rats. Male Wistar rats (255‐265g) were divided: lean control (CTR); obese sedentary (OBSD); and obese trained (OBTR). Exercise training (treadmill at 60% maximal velocity, 60min, 5 days/week) started after 4 weeks of cafeteria diet consumption and was carried out for further 7 weeks. OBSD rats had increased insulin, glucose, leptin, hepatic triglycerides, malondialdehyde, and reduced endothelium‐dependent relaxation compared with CTR rats. OBTR rats had lower insulin (about 63%), glucose (29%) and leptin (81%) concentration compared with OBSD. Improvement in vascular relaxation (about 34%) and lower formation of oxygen species in aorta from trained rats were also seen. Beside this, lower hepatic triglycerides (80%) and malondialdehyde formation (46%) were seen in OBTR. These benefits were related to reduction in epididymal fat pad mass (R2=97%, P=0,002). This physical exercise protocol was effective to prevent metabolic and vascular disorders induced by cafeteria diet consumption.

Grant Funding Source: Supported by São Paulo Research Foundation
Moderate aerobic exercise training recovers disorders in white skeletal muscle induced by chronic kidney disease in rats (884.16)
Authors: de Moraes Wilson , Souza Pamella , Paixao Nathalie , Bozi Luiz , Guimaraes Fabiana , Irigoyen Maria , Brum Patricia , Medeiros Alessandra
Published: June 2021

Chronic kidney disease induces weakness and muscle skeletal dysfunction preferentially in white muscle fibers. Moderate aerobic exercise training (AET) is known for recovers these alterations. However, the mechanisms are no completely elucidated. Adult Wistar rats were evaluated in 4 groups: Sham, Sham trained (Sham+AET), and 5/6 nephrectomy trained (CRF+AET) or not (CRF). Exercised rats were submitted to treadmill exercise for 60 min, 5 times/wk for 60 days. We evaluated motor performance (tolerance to exercise in treadmill and rotarod), cross sectional area (CSA) and parameters related‐protein control quality (accumulated ubiquitinited and misfolded proteins), chymotripsin‐like proteasome activity (UPS activity), genes markers of unfolded protein response (ATF4, GRP78, XBP‐1), GRP78 protein expression and redox balance (carbonilated proteins and lipid hidroperoxides) in tibialis anterior muscle. Despite the CSA were not different between groups, the CRF presented a reduction in motor performance and tendency to muscle atrophy, which was followed by increased in UPS activity, accumulated ubiquitinited and misfolded proteins and increased in ATF4 and GRP78, but no in XBP‐1 gene expression, as well as increased in GRP78 protein levels compared to Sham. In CRF+AET we observed restoration in exercise tolerance, accumulated ubiquitinited and misfolded proteins, UPS activity and increased in ATF4 and GRP78 genes and GRP78 protein levels accompanied by an increase in lipid hidroperoxidation and reduction in carbonilated proteins. These results suggest that an unfolded protein response is activated in white muscle fibers of chronic kidney disease in rats independently of atrophy and that AET promoted this response, probably for induced adaptation protecting against uremia chronic induced‐cellular stress.

Grant Funding Source: Supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Heart failure patients have impaired thermoregulatory response during exercise (884.2)
Authors: Morris Norman , Royston Danielle , Jayasinghe Rohan , Sabapathy Surendran
Published: June 2021

Objective: During a thermoregulatory challenge such as exercise in the heat, skin blood flow (SkBF) must rise so as to maximise radiant, convective and evaporative heat loss. There is some evidence to suggest that in Heart Failure (HF) the rise in SkBF is blunted during passive heat exposure. Indeed, HF patients may be unable to adequately increase cardiac output to service multiple vascular beds during a thermoregulatory challenge. The aim of this study was to compare the thermoregulatory responses to exercise in the heat in a group of HF patients (n=7, 62 + 7 yr, NYHA Class I‐II) and age‐matched healthy controls (CON; n=6, 63 + 8 yr). Methods: HF and CON exercised for 60 min heat (30oC, 60% relative humidity) at ~70% peak oxygen uptake (VO2). Core temperature (Tc) and skin temperature (Tsk) were measured continuously. Skin blood flow was measured every 10 minutes using Laser Doppler Flowmetry. Skin conductance was determined from the ratio of SkBF and mean arterial pressure. Results: HF patients exercised with a significantly (p<0.05) lower metabolic heat load when compared to CON (VO2: HF 1.26 + 0.32; CON 1.83 + 0.52 l/min). Despite this, both HF and CON had a similar and significant increase (P<0.05) in Tc (HF: pre: 37.2+ 0.4, end ex: 38.2 + 0.4oC; CON: pre 37.3 + 0.2, end ex: 38.2 + 0.4oC) and Tsk (HF: pre: 33.0+ 0.6, end ex: 35.0 + 0.5oC; CON: pre 32.6 + 0.6, end ex: 35.7 + 0.6oC). HF patients had a significantly lower (p<0.01) increase in SkBF (HF: 101 + 30; CON: 302 + 64 AU) and skin conductance (HF: 1.0 + 0.6; CON: 2.9 + 1.1 AU). Conclusion: Despite exercising at a lower metabolic heat load, HF patients had a similar increase in Tc but lower SkBF when compared CON. Our results suggest HF patients may have impaired thermoregulation secondary to blunted circulatory heat dissipation in HF.
The effect of cachectic myofiber metabolic properties on the resistance exercise‐induced hypertrophy response (884.21)
Authors: Mangum Joshua , Hardee Justin , Puppa Melissa , Carson James
Published: June 2021

Cancer cachexia disrupts skeletal muscle metabolism in conjunction with the loss of mass. There are no approved treatments for cachexia however our lab has shown treadmill exercise can suppress wasting. The purpose of this study was to determine the relationship between myofiber metabolic properties and eccentric exercise induced myofiber hypertrophy in mice with cancer cachexia. 16‐week male C57BL/6 (WT) and ApcMin/+ (Min) mice performed resistance exercise (RE) by stimulating the sciatic nerve for 7 sessions over 2 weeks. The tibialis anterior (TA) was contracted (EX) in one leg and the contralateral served as a control (CN). Histological analysis was used to examine myofiber SDH activity and PAS staining. Cachexia reduced TA mass and myofiber cross sectional area (CSA), RE was able to increase TA mass and myofiber CSA (EX > CN). RE induced a 26% increase in the frequency of high SDH activity fibers (OX), which were reduced with cachexia. While cachexia reduced the CSA of both OX and low SDH activity (GL) fibers, RE selectively induced hypertrophy of GL fibers. In addition, cachexia induced a 38% increase in the frequency of high glycogen content (HG) fibers. Although RE did not alter HG fiber frequency, RE induced hypertrophy of HG fibers. In summary, cachexia‐induced myofiber atrophy is independent of myofiber SDH activity. However, RE during cancer cachexia can increase OX fiber frequency and reverse GL fiber wasting.

Grant Funding Source: Supported By R01CA121249
Aerobic fitness and limiting factors of maximal performance in chronic low back pain patients (884.26)
Authors: Duque Ivan Leonardo , Urrutia Isabella , Duvallet Alain
Published: June 2021

Objective: To determine the level of cardiorespiratory fitness in patients with chronic low back pain and to establish factors limiting the maximal effort during the ergometry Methods: Patients performed a maximal exercise test to measure V ̇O2max. Clinical endpoints of the tests were determined and grouped as maximal effort and symptom‐limited effort.

Results: 101 patients aged 29.8 achieved a V ̇O2max value of 30 ml.kg‐1.min‐1. When compared to normative categories, men and women were situated in the fair category. Quadriceps/leg fatigue was the most frequent limiting factor. Symptom limited effort endpoints were reported by 54.4% of the subjects. An association between the clinical endpoint and the accomplished V ̇O2 value was established. Maximal effort is associated with a V ̇O2max value while symptom‐limited effort is associated with a V ̇O2peak value.

Conclusions: Clinical limiting factors of maximal exertion interfere the achievement of maximal oxygen uptake in patients with chronic low back pain. Further, there exists an association among the clinical endpoints of the tests and the V ̇O2 value achieved. Chronic low back pain patients have a lower level of aerobic fitness than healthy controls.
Development of protocols to estimate maximal oxygen consumption and body composition in individuals with spinal cord injury (884.27)
Authors: Terson de Paleville Daniela , Lorenz Douglas , McCulloch John , Aslan Sevda , Kloby Michael , Love Matthew , Walden Amy , Harkema Susan
Published: June 2021

Cardiovascular complications and obesity are common secondary complications after spinal cord injury (SCI). The measurement of VO2max during graded exercise test is the gold standard to evaluate cardiovascular fitness. Due to the complexity and cost of VO2max measurements, regression equations to estimateVO2max from submaximal tests based on heart rate have been developed. Due to sympathetic impairments secondary to SCI heart rate may not be an accurate tool to use to predict VO2 max in SCI. The aim of this study was to validate a submaximal test based on Ratings of Perceived Exertion (RPE) to predict VO2max for people with SCI. A second aim of this study was to validate current skinfold equations to estimate percentage of body fat (%fat) in this population. Methods: 10 able‐bodied and 12 SCI individuals participated in this study. The standardized test protocols for VO2 max were performed on a total body recumbent stepper (NuStep T4 ergometer). Analysis of the expired gases occurred every 10 seconds. Heart rate was recorded using a Polar heart rate monitor and 3‐lead ECG. RPE was recorded using the Borg 6‐20 scale. Estimation of %fat by skinfold measurements in supine position were compared with values obtained by DXA scans. Results: There was a strong positive correlation between predicted and observed VO2max in able‐bodied subjects using RPE (ρ = 0.86; p蠄0.05) and RPE + watts (ρ = 0.88; p蠄0.05). SCI subjects were able to perform both, the maximal and submaximal protocols, with a cadence of 80 steps per minute. Current validated skinfolds equations underestimate %fat in SCI individuals. Conclusions: The results of this study show promise for the development of submaximal RPE‐based protocols for the prediction of VO2max in this population. Future directions include the examination of protocols ending at RPE 13 and RPE 15 as well as to develop prediction equations for a larger group of individuals with varying levels and severity of SCI. New prediction equations to estimate %fat for SCI need to be developed.
Effects of chronic exercise on doxorubicin‐induced thymic damage (884.4)
Authors: Quinn Colin , Gibson Noah , Bashore Alex , Bredahl Eric , Hayward Reid , Hydock David
Published: June 2021

The anthracycline antibiotic doxorubicin (DOX) has been shown to cause thymic involution and concurrent decreases in thymocyte (T‐cell) number. Acute exhaustive exercise has shown similar decrements in the thymus, with increases in lipid peroxide and decreased free‐radical protective enzymes; however, submaximal exercise has been shown to enhance viable T‐cell number. The purpose of this study was to examine the effects of endurance exercise training prior to DOX administration on thymus size, viable T‐cell number, and measures of oxidative stress. Ten week‐old Sprague‐Dawley rats were randomly assigned to an exercise group or a sedentary group for 10 weeks. After the activity treatment period, animals received DOX or saline as a control. Seventy‐two hours after injections, the thymus was excised, and T‐cells were isolated for cell count. Oxidative stress in thymic tissue was measured using a lipid peroxidation kit for measures of malondialdehyde (MDA). Exercise training attenuated the increased levels of MDA found in rat thymus following acute administration of DOX. The results suggest that endurance training may play a role in protecting the thymus from DOX‐induced damage.
Multidrug resistance protein expression is not associated with the myoprotective effects of exercise preconditioning against doxorubicin‐induced toxicities (884.6)
Authors: Gibson Noah , Pfannenstiel Keith , Quinn Colin , Hydock David , Hayward Reid
Published: June 2021

Previously, we reported that exercise preconditioning increases myocardial multidrug resistance protein (MRP) expression and decreases doxorubicin (DOX) accumulation. Therefore, we hypothesized that the same would be observed in skeletal muscle. Male Sprague‐Dawley rats were randomly assigned to undergo 10‐weeks of voluntary wheel running (WR) or remain sedentary (SED). Following the 10‐weeks of running or inactivity, rats were further randomized to receive a 15 mg/kg body weight bolus i.p. injection of DOX or equivalent volume of saline (SAL). Twenty‐four hours following DOX or SAL treatment rats were euthanized, soleus (SOL) and extensor digitorum longus (EDL) muscles were excised and snap frozen in liquid nitrogen. DOX accumulation, MRP expression, and lipid peroxidation were analyzed. Our results suggest that DOX accumulation is significantly reduced with WR in the SOL (p<0.05; 505±99 ng/g vs. 626±86 ng/g) but not in the EDL (p>0.05; 219±89 ng/g vs. 287±85 ng/g). A reduction in malondialdehyde (MDA) was observed in the SOL (p<0.05; 2.36±0.8 µg/mg vs 4.09±1.4 µg/mg) and the EDL (p<0.05; 1.15±0.32 µg/mg vs. 1.74±0.34 µg/mg) with WR. In contrast, no significant differences were observed (p>0.05) in SOL or EDL MRP expression between groups. These data suggest that while exercise preconditioning reduces DOX accumulation and lipid peroxidation, the myoprotection is independent of MRP expression.