bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Pelvic Afferent Nerves Are Responsible for Greater Resting and Evoked Vasoconstrictor Tone in Individual Rats
Authors: Knuepfer Mark M , Hoffman‐Schepers Nicole B , Perry Jeffrey L
Published: November 2023

Greater acute pressor responsiveness to behavioral stress has been observed in those patients susceptible to the development of essential hypertension. Likewise, differences in resting sympathetic tone have been observed with greater tone reflected in higher systemic vascular resistance in many hypertensive patients or those prone to develop hypertension. Since renal denervation (RDN) has been reported to reduce arterial pressure in some patients with resistant hypertension, we sought to define the role of the renal nerves in determining resting and evoked vasoconstrictor tone. We hypothesized that RDN or selective renal pelvic deafferentation (RPDA) would prevent differences in resting vasoconstrictor tone, presumably sympathetic, and prevent greater vasoconstrictor responsiveness to startle in those rats that are hyperreactors to stress. Outbred male Sprague‐Dawley rats were instrumented for arterial pressure, heart rate and cardiac output determination. After recovery, rats were tested for their cardiovascular responsiveness to air jet (20 psi, 1–2 sec) and to cold water stress (1 cm deep for 1 min). Rats were separated into those with larger pressor responsiveness (LP) to startle with air jet or cold water and compared to those with smaller pressor responses (SP). Sympathetic tone was estimated by responses to administration of hexamethonium (20 mg/kg) and by pentolinium (10 mg/kg). LP had greater reductions in arterial pressure after ganglionic blockade due to greater falls in calculated systemic vascular resistance. Subsequently, rats underwent either RDN with extracorporeal radiofrequency ablation of the renal artery (100 KHz, <1 mW, 20 sec duration, 4–6 times/artery) or RPDA with capsaicin infusion in the renal pelvis. One week later, rats were retested for stress responsiveness and sympathetic tone. Either RDN or RPDA prevented the differences observed in pressor responsiveness to startle such that there was no difference between SP and LP. In addition, there were no longer differences between SP and LP in resting vasoconstrictor tone determined with ganglionic blockade. These data suggest that renal pelvic afferent nerves are responsible for greater stress‐induced vasoconstrictor responses and higher vasoconstrictor tone in a subset of rats (LP). We propose that RDN acts selectively in hyperreactors to acute stress (LP) and lowers their overall resting and evoked vasoconstrictor tone to reduce arterial pressure in hypertension due to pelvic afferents. These data suggest that RDN or selective RPDA may be more efficacious in treating this cohort of the population with essential hypertension.

Support or Funding Information

Supported by St. Louis University
The Effect of Humor Associated Mirthful Laughter Combined with Quiescence on Modulating C Reactive Protein Blood Levels: A Pilot Study
Authors: Bains Gurinder Singh , Berk Lee , Lohman Everett , Daher Noha , Alahmadi Bara , Jadav Dhara , Alsultan Alanood , Alghamdi Ahmed
Published: November 2023

Introduction

With an increase in life expectancy, there exists a need for whole‐person care that enhances Quality of Life. Humor associated mirthful laughter has proven to yield numerous whole person health related benefits such as lowering the stress hormone cortisol and improving vascular function. High sensitivity C Reactive Protein (hs‐CRP) is an inflammatory biomarker. There are no known studies that have shown an association between humor associated mirthful laughter and changes in acute hs‐CRP blood levels.

Purpose

The purpose of this study was to evaluate the effect of humor associated mirthful laughter on acute CRP modulation in a humor group vs. a non‐humor control group.

Methods

Thirty two healthy adults were recruited and enrolled (humor group n = 16; control group n = 16). The humor group consisted of 8 males and 8 females with a mean age of 26.4 ± 4.4 years. The control group consisted of 8 males and 8 females with a mean age of 26.6 ± 2.9 years. The hs‐CRP levels were obtained through a finger stick blood test. The hs‐CRP levels were collected at three time points; immediately after signing the informed consent, immediately after watching a 20 minute humor video or sitting quietly for 20 minutes, and after 20 minutes of quiescence after the second hs‐CRP test. Blood pressure and heart rate were taken immediately before the first hs‐CRP sample and then five minutes after the first, second, and third hs‐CRP measurement. The humor group self‐selected a humor video of either 20 minutes of Russell Peters standup comedy or a montage of America's Funniest Home Videos. The control group sat quietly for 20 minutes and were not allowed to read, talk, sleep, or use their cell phone.

Results

There were significant differences in mean CRP levels, systolic blood pressure, and heart rate over time (p=0.04, p=0.01, and p< 0.001, respectively). For the humor group, 1) CRP levels decreased from 1.65 ± 0.3 mg/L at baseline to 1.42 ± 0.3 mg/L post humor (p=0.05), 2) systolic blood pressure decreased from baseline to humor + quiescence (p=0.02), and 3) heart rate decreased from baseline to post humor (p=0.01) and baseline to post humor + quiescence (p=0.001).

Conclusions

The overall, complimentary health benefits of combining enjoyable humor associated mirthful laughter with a quiescent period showed a decrease in inflammation (hs‐CRP), systolic blood pressure, and heart rate and thus, is more beneficial than being quiescent alone. Our pilot research shows potential clinical and rehabilitative benefits that can be applied to whole person wellness programs. Humor and laughter appear to be beneficial, thus providing components in enhancing Quality of Life. Further research will be done to expand these positive findings.
Slow breathing reductions in mean arterial pressure are dependent on psychological characteristics
Authors: Kelly Kevin L , Lin Jeff , Poteracki James M , Adams Katelynn M , Kelly Catherine A , Wegner Brian J , Newhouse Lauren P , Moser Jason S , Wehrwein Erica A
Published: November 2023

Slow‐paced breathing has been reported to reduce blood pressure, but there are conflicting results over the efficacy of device guided (DG) vs self‐paced (SP) slow breathing. We hypothesized that a reduction in breathing rate is not the only factor contributing to changes in autonomic and cardiovascular parameters, but there is an interaction between the methods (SP vs DG) and psychology of the user that influence outcomes. Comparison of DG (n=10) and SP (n=11) slow breathing in young healthy males showed that psychological traits were correlated with reductions in mean arterial pressure (MAP) differentially. At baseline, there was no difference in breathing rate between SP and DG (14.36±1.03 vs 15.39±1.29 breaths per minute, p=0.27) and respiratory rate was reduced to 8.36±0.74 breaths per minute (BPM) in the SP group (p<0.01) and to 6.37±0.10 BPM in the DG group (p<0.01). The two groups differed significantly during slow breathing (p<0.01 between groups). With respect to our primary hypothesis, lower trait anxiety was related to reductions in MAP in the SP group (r=0.452, p=0.081), but marginal increases in the DG group (r=−0.301, p=0.199). Higher reported cognitive functions were related to decreases in in MAP in the SP group (r=−0.498, p=0.059), but not in the DG group (r=0.092, p=0.400). Finally, the tendency be aware of one's surrounding was related to decreases in MAP in the SP group (r=0.683, p=0.010), but an opposing increase in MAP in the DG group (r=−0.472, p=0.084). SP and DG are inherently different and are highly influenced by psychological characteristics. Future use of these two breathing techniques to reduce blood pressure should take into account individual differences in psychological characteristics in order to maximize benefits.
Cardiovascular and behavioral sequelae of witnessing social defeat stress in male and female rats
Authors: Lombard Calliandra M , Melson Michael N , Fadel Jim R , Wood Christopher S , Wood Susan K
Published: November 2023

It is well recognized that exposure to social stress can contribute to psychosocial disorders (ie., depression) and comorbid medical disorders such as cardiovascular disease. While animal models of social defeat stress traditionally utilize a physical confrontation, recent studies have indicated that the psychological stress of witnessing the stressful event has long lasting behavioral consequences. In the present study we used the resident‐intruder paradigm to contrast the depressive‐like and cardiovascular consequences of social defeat stress in male Sprague Dawley rats that were directly exposed to the aggressive resident (intruder) with either male or female rats that were present in the cage, but only observing the stressful event (witness). Rats were implanted with cardiovascular transmitters that allowed for simultaneous measurements of blood pressure and ECG in two rats within the same cage (Data Sciences Intl). Following surgical recovery, rats were assigned to one of three groups; control, 5 consecutive days of social defeat (intruder, male), or observation of social defeat (witness, male or female) for 15 mins/day. For all experimental groups, cardiovascular telemetry was collected 24 hrs/day and continuous recordings were collected on the 1st and 5th exposure to stress/control. Five days after the final stress exposure all experimental rats were also subjected to the sucrose preference test to assess stress‐induced anhedonia. In agreement with our previous findings, social defeat stress produced a robust tachycardic and pressor response. Interestingly, the magnitude of increased blood pressure (MAP) and heart rate (HR) over controls was comparable between intruder and male witness rats. However, 12 hr light/dark cycle measurements revealed significantly greater increases in resting HR and MAP in male witness rats compared with controls and intruders. Female witness rats, on the other hand, exhibited blunted cardiovascular responsivity to social stress exposure compared with males and showed no long‐lasting changes in resting HR and MAP that was displayed in male witnesses. Importantly, assessment of depressive‐like behaviors using the sucrose preference test revealed that male witness rats displayed exaggerated anhedonia compared with male intruder rats while females again appeared unaffected. Taken together, these findings reveal that although females were generally unaffected by witnessing social defeat stress, in males, witnessing this social stressor may have a greater impact on the cardiovascular system and resulting depressive‐like behavior compared with experiencing the direct physical contact of social defeat stress.

Support or Funding Information

Research supported by 15SDG22430017 and P20GM103641.
Effects of Essential Oil on Fear Memory and the Immune Response; A Potential Alternative Therapy for Post‐Traumatic Stress Disorder (PSTD)
Authors: Moshfegh Cassandra , Swiercz Adam P , Hopkins Lauren , Marvar Paul J
Published: November 2023

Stress and anxiety‐related mental health disorders such as post‐traumatic stress disorder (PTSD) are on the rise. Stress is known to modify the immune system. Despite the growing literature on immune system changes associated with direct stressors, the relationship between fear memory and the immune system has not been well characterized. Moreover, there are only two FDA‐approved medications for PTSD. Orange essential plant oil (OEPO) has been previously found to have CNS depressant‐like effects in mice. Therefore we examined the effects of OEPO on fear memory and immune cell activation in a mouse model of PTSD (Pavlovian Fear Conditioning). The treatment group (n=8) was administered 25% OEPO via olfactory exposure prior to and after fear conditioning. Mice exposed to 25% OEPO showed no difference in percent freezing during fear acquisition compared to controls. However, when tested for extinction retention 48 hours later the treatment group experienced a 17.21 ± 1.58 % (p < 0.01) significant decrease in freezing behavior versus control (3.67 ± 2.13%), suggesting that OEPO affects extinction of fear memory in mice. This appears to be independent of a shift in immune cell activation as treatment and control mice showed similar levels of splenocyte derived naïve / effector lymphocytes and antigen presenting cells. Both groups however showed increased levels of naïve T cells CD62hiCD44lo 56.9(± 0.83)% relative to non‐fear conditioned mice 46.3 (± 3.16)% (p < 0.01). These data suggest that OEPO enhances extinction of fear memory while its affects on the immune system remain unclear.

Support or Funding Information

NIH R00 HL107675‐03
Exercise and Isoproterenol‐Induced Cardiac Hypertrophy in Aged Mice
Authors: Luckey Stephen , McLaughlin Nathan , Soo Sherilynn
Published: November 2023

Approximately half of the people with heart failure are older than 75 year of age. Despite this statistic, and the fact that the aged heart undergoes changes that impact its structure and function, the vast majority of heart failure research is conducted using young animal models. Therefore, the objective of this study was to investigate how age‐related changes affect the ability of the heart to adapt to physiological (e.g. exercise) and pathological (e.g. heart failure induced by beta adrenergic stimulation) stimuli. CB6F1 male mice at 22 months of age were used for this investigation. Mice were divided into four groups: sedentary, voluntary exercise, vehicle, and isoproterenol. We assessed exercise capacity and found that these mice voluntarily ran on a cage wheel and, on average, ran 2.4 ± 0.3 km and spent 2.9 ± 0.4 hours per day on the wheel. Wheel running speed was 0.8 ± 0.1 km/hr when averaged over the 3‐week period. Although mice had a slight, but insignificant increase in heart weight‐to‐tibial length ratio (HW/TL), exercise induced a 13% increase in left ventricle‐to‐tibial length ratio (LV/TL). Mini‐osmotic pumps delivered vehicle or isoproterenol (30mg/kg/day) for 14 days. Isoproterenol treatment resulted in a 10% and 13% increase in HW/TL ratio and LV/TL ratio, respectively. In conclusion, these investigations suggest that the aged left ventricle has the ability to undergo cardiac hypertrophy following physiological or pathological stimuli. We are currently investigating the underlying molecular and cellular mechanisms that play a role in the observed cardiac adaptations.

Support or Funding Information

M.J. Murdock Charitable Trust (S.W.L.)
Myocardial Glycolytic Rate Regulates Exercise‐Induced Physiologic Cardiac Growth
Authors: Gibb Andrew , Gilbert Lindsey A , Brittian Kenneth R , Jones Steven P , Bhatnagar Aruni , Hill Bradford G
Published: November 2023

BACKGROUND

Regular exercise improves quality of life and decreases all‐cause mortality, in part due to improvements in cardiovascular health. Repetitive exercise enhances cardiac function by promoting cardiomyocyte growth and increasing angiogenesis, and is associated with elevated myocardial glucose and fatty acid utilization. Nevertheless, it is unclear whether changes in myocardial metabolism are causative in cardiac adaptations to exercise. In this study, we tested the hypothesis that exercise‐induced increases in myocardial glycolysis are required for physiological cardiac growth.

METHODS

Fifteen week‐old, male FVB/NJ transgenic (Tg) mice expressing a cardiac‐specific, dominant‐negative form of phosphofructokinase 2, which decreases myocardial glycolytic rate, and their wild‐type (WT) counterparts were subjected to sedentary (SED) conditions or forced treadmill exercise (EXE) for 30 days. Systemic and cardiac‐specific adaptations to exercise were assessed by measuring exercise capacity and echocardiographic changes in cardiac structure and function; biochemical signatures of adaptation were measured by immunohistochemistry, qPCR and immunoblotting.

RESULTS

In WT mice, exercise training increased distance run by 42% (p<0.0001) and work performed by 69% (p<0.0001). Exercise promoted cardiac growth (heart‐to‐tibia length: SED, 6.7±0.2 mg/mm vs. EXE, 7.7±0.4 mg/mm; p<0.0001), which was due to myocyte hypertrophy (myocyte cross‐sectional area: SED, 461±43 μm2 vs. EXE, 564±40 μm2; p<0.01). Exercise capacity was not different between WT and Tg mice; however, unlike WT EXE mice, which showed increased end diastolic volume, stroke volume, and cardiac output after exercise (p<0.05), exercise did not change these indices of cardiac function in Tg mice. Interestingly, the Tg SED and EXE mice displayed a hypertrophic heart, characterized by elevated atrial natriuretic peptide (p<0.01), indicating activation of a fetal gene program. Moreover, unlike WT mice, Tg mice failed to show exercise‐induced activation of Akt, which is necessary for physiological cardiac growth and adpatation, and demonstrated lower expression of the pro‐angiogenic factor, VEGF.

CONCLUSIONS

Diminished cardiac glycolytic rate prevents cardiac adaptations to exercise and may act as a pivotal regulator of physiological and pathological hypertrophic programs.

Support or Funding Information

ACKNOWLEDGEMENTS: This work was funded by the NIH (GM103492 and HL122580).
Satellite Cell Behavior in Cyclists Following Intensified Training With and Without Protein Supplementation
Authors: Luden Nicholas , McKenzie Alec , Saunders Michael , Womack Christopher , D'Lugos Andrew , Gworek Keith
Published: November 2023

Our objective was to investigate the satellite cell (SC) response of endurance‐trained cyclists (n=8) to 10 days of intensified cycle training (ICT) and 10 days of subsequent recovery (RVT – reduced volume training), with carbohydrate (CHO) and carbohydrate‐protein (PRO) supplementation. Muscle biopsies were obtained from the vastus lateralis before and after ICT and RVT. Immunofluorescent microscopy was used to analyze SCs and myosin heavy chain (MHC) I and IIa. Data were analyzed using magnitude‐based inferences. MHC I SCs were abundant at baseline (38 ± 20 SCs/100 fibers), decreased (unclear) from PRECHO to ICTCHO, and then likely increased by 60 ± 64% following RVTCHO. No other changes in SC content were observed. Myonuclear content of MHC I fibers most likely increased (16 ± 6%) from baseline to ICTCHO. Likewise, MHC IIa myonuclear content likely increased (14 ± 14%) from PRECHO to RVTCHO. Though there were no changes in fiber size (cross sectional area) under CHO conditions, ICT with PRO supplementation very likely increased MHC I size (14 ± 8%) and likely increased MHC IIa size (16 ± 19%). Trained endurance cyclists possess a relatively large pool of SCs that appeared to facilitate myonuclear accretion with heavy training under carbohydrate conditions. These data strengthen the growing body of evidence demonstrating the non‐hypertrophic role of SCs in skeletal muscle and the possible benefit of protein supplementation.

Support or Funding Information

This project was supported by James Madison University's College of Health and Behavioral Studies Faculty Research Grant (N. Luden and A. McKenzie) and the Dairy Research Institute (N. Luden and M. Saunders).
Human Physiological Performance During a 1 Mile Swim in Cold Water
Authors: Treu Spencer P , Cummings Katelyn M , Olson Mariah F , Connell Jennifer M , Malone Christopher J , Barkai Ram , Wilson Ted
Published: November 2023

Human physiological responses to cold water swimming (≤5°C) are poorly characterized. A database (www.internationaliceswimming.com) describes 1 mile ice swimming performance times and swim conditions. This study analyzed data from 71 male and 17 female persons who completed 1 mile ice swims. Swim completion time was 33.9 ± 6.0 minutes for males and significantly slower for females at 36.2 ± 7.8 minutes. Increased age for females may be associated with a more robust increase in swim times relative to males whose swim times were less detrimentally affected by increasing age. A subset of swimmers completed multiple 1 mile swims (n=24), and the second swim time was significantly faster than the first, although improvements were not observed for additional swims. Cold exposure from increasing wind chill has been suggested to have a detrimental effect on cold water swim time, and was associated with an increased swim time that approached significance (P = 0.06). Water temperatures below 50C had no statistically significant effect on swim completion time. In summary, ice swimming is increasing in popularity with consideration for future Winter Olympic activities. Characterization of ice water exposure physiology remains an important consideration for emergency, military, and medical personnel. This data set provides a useful benchmark for understanding and predicting physiological performance during exposure to cold environmental conditions.
Relationship between Maximum Oxygen Consumption and Muscle Oxygenation During a Cross Country Season
Authors: McCready Trevor A , Arnold Kaitlyn E , Davis John E
Published: November 2023

The purpose of this study was to examine the relationship between maximum oxygen consumption and muscle tissue oxygenation of collegiate cross country runners throughout their season. Seven collegiate cross country runners (six female and one male, 18.8±0.9 yrs) were studied early season (T1), mid season (T2), directly after their last meet (T3), and one week after their season was completed (T4). Each subject completed a graded exercise test to exhaustion on a motor driven treadmill. Subjects began running at seven mile per hour for two minutes. The elevation of the treadmill was gradually increased to volitional fatigue. A Parvo Medics TrueOne 2400 metabolic measurement system was used to determine oxygen consumption, expired ventilation, and respiratory exchange ratio at each exercise level and at maximum. Maximum oxygen consumption (VO2max) was then determined. Near‐infrared spectroscopy (Portamon, Artinis Inc.) was used to measure oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin, and tissue saturation index (TSI) for each stage of the graded exercise test. The Portamon was placed over the vastus lateralis and secured. TSI is used as an index of muscle tissue oxygenation. In this study, the slope of the decline in TSI was determined and used to quantify the muscle oxygenation response. TSI data was smoothed via a moving average filter width of 5 seconds. The moving average filter calculates the unweighted mean of the measured data over the filter width. Overall, the TSI deceased at a slower rate during mid season (T2) compared to the early season (T1) testing (Slope: T1=−0.091±0.016; T2=−0.021±0.007). Furthermore, VO2 Max increased between T1 to T2 (VO2 Max: T1=58.5±9.1 ml//kg/min; T2=62.35±12.03 ml/kg/min). Muscle oxygenation declined at the fastest rate during the early part of the cross‐country season relative to mid‐season. At the same time, VO2max significantly increased between those two time points. Taken together, this suggests that adaptive changes as result of cross country training enables runners to be more efficient at utilizing oxygen probably as a result of adaptive metabolic changes in skeletal muscle.
Combined Exercise Training Promotes Additional Benefits Than Aerobic or Resistance Training in a Model of Metabolic Syndrome and Menopause
Authors: Conti Filipe F , Brito Janaina O , Dias Danielle S , Bernardes Nathalia , Malfitano Christiane , Irigoyen Maria‐Claudia , De Angelis Kátia
Published: November 2023

The aim of this study was to verify the effects of three different moderate exercise training protocols (aerobic, resistance and combined (aerobic + resistance)) in a model of metabolic syndrome and menopause on a cardiovascular parameter and oxidative stress. Female SHR rats were divided into (n=8): hypertensive (H), hypertensive ovariectomized submitted to fructose overload (100g/L in drinking water) (HFO), aerobic trained hypertensive ovariectomized submitted to fructose overload (AHOF), resistance trained hypertensive ovariectomized submitted to fructose overload (RHOF) and combined trained hypertensive ovariectomized submitted to fructose overload (CHOF). Arterial pressure (AP) signals were directly recorded. Vascular autonomic modulation was evaluated by spectral analysis. The cardiac oxidative stress was evaluated by chemiluminescence (CL) determination. The association of fructose overload and hormone deprivation promoted an increase in AP (HOF: 174±4 vs. H: 146±4 mmHg), heart rate (HOF: 393±10 vs. H: 352±13 bpm), LF‐SAP (HOF: 10.6±2.3vs. H: 5.0±0.9 mmHg2) and CL. On the other hand, all exercise training protocols were able to reduce the CL and LF‐SAP. It was noted that only the combined exercise training reduced the AP (CHOF: 158±4 mmHg) and the heart rate (CHOF: 303±5 bpm). In all, fructose overload induced impairment in hemodynamic, vascular autonomic control and increased oxidative stress in hypertensive rats submitted to ovarian hormones deprivation. However, all exercise training protocols showed a beneficial role. Moreover, the combined exercise training showed additional improvement, suggesting that this could be a better approach than isolated aerobic and resistance training.

Support or Funding Information

FAPESP ‐2011/15828‐9; 2010/17188‐4; 2012/20141‐5 CNPq ‐ 479766/2011‐8
Reversing the effects of chronic stress on the aorta with exercise training
Authors: Lemaster Kent , DeVallance Evan , Branyan Kayla , Skinner Roy , Brooks Steve , Asano Shinichi , Killmer Cameron , Olfert Mark , Bryner Randall , Frisbee Jefferson , Chantler Paul
Published: November 2023

Individuals with increased levels of chronic stress have an increased aortic stiffness which is a strong, independent risk factor for cardiovascular disease. Additionally, chronic stress is associated with a decreased capacity for endothelium‐dependent, nitric oxide (NO)‐induced vasorelaxation which may contribute to the aortic stiffness and increased after load on the heart. Using the unpredictable chronic mild stress protocol (UCMS), lean zucker rats (LZR; healthy rats) develop impaired vascular reactivity in aortic rings concomitant to the onset of chronic stress pathologies. Therapeutic interventions aimed at improving endothelial functioning are therefore considered important avenues for improving CV outcomes in stressed patients. We hypothesized that a chronic aerobic exercise intervention would improve endothelium‐dependent relaxation to methacholine in isolated aortic rings of stressed LZRs. A total of 22 LZRs underwent 8 weeks of a treadmill exercise protocol beginning at 9 weeks of age. The animals were separated into 4 groups: sedentary LZR (LZR; n=7); UCMS LZR (UCMS‐LZR; n=8); exercise and UCMS (ExUCMS‐LZR n=7). Following the intervention, the thoracic aorta was dissected out from each animal and sectioned into rings, some of which were then mounted into an ex vivo wire tension myograph system. The remaining rings were evaluated for NO production in a DAF‐FM diacetate assay. Force transduction was used to measure the changes in aortic tension in response to pharmacological agonists. The aortic rings were mechanically set to 1 gram of tension then pre‐constricted using phenylephrine (1×10‐6μM), followed by a gradual dilation induced by increasing concentrations of methacholine (1×10‐9, 1×10‐8, 1×10‐7, 1×106, 1×10‐5 μM respectively). The LZR group demonstrated greater methacholine‐induced maximal vasorelaxation compared to the UCMS‐LZR group (83% vs. 78%). The ExUCMS‐LZR group experienced the greatest maximal dilation (90%) as well as increased values of NO production measured in the DAF assay compared to LZR group and UCMS‐LZR group. These results demonstrate that 8 weeks of aerobic exercise enhances endothelial bioavailability and/or production of NO which improves endothelium‐dependent vasorelaxation in the aortas of stressed LZRs even more so than the sedentary control. Exercise training may therefore be an important therapy for promoting greater arterial compliance of chronically stressed individuals.

Support or Funding Information

NIH

AHA
Changes in physical strength, activity of daily living, life satisfaction, and self‐esteem after performing the physical and psychological exercise program in older adults with hemiplegia
Authors: Park Sang Gil , Moon Hwasil , Jin Haeng Mi
Published: November 2023

The purpose of this study was to assess the impact of the physical and psychological exercise program on physical strength, activity of daily living, life satisfaction, and self‐esteem in older adults with hemiplegia. A total of 14 older adults with hemiplegia (age range: 60–80 years) participated in the physical and psychological exercise program during 12 weeks, twice a week, and 60 minutes each time. Changes of physical strength, activity of daily living (ADL), instrumental activity of daily living (IADL), life satisfaction, and self‐esteem were observed between pre‐ and post‐program. After performing the physical and psychological exercise program, muscular strength and flexibility of both lower body and upper body was increased. Quickness and dynamic balance were also improved after physical and psychological exercise program. Using validated questionnaires, ADL and IADL were assessed and both ADL and IADL scores were decreased after physical and psychological exercise program (ADL: 15.8 ± 4.2 vs. 13.3 ± 2.7 au; IADL: 18.6 ± 4.9 vs. 47.9 ± 4.4 au), which indicates improvements in activity of daily living. Performing the physical and psychological exercise program also improved the life satisfaction and self‐esteem in older adults with hemiplegia (life satisfaction: 12.3 ± 1.6 vs. 14.9 ± 2.2 au; self‐esteem: 23.2 ± 3.4 vs. 29.9 ± 4.4 au). In conclusion, physical and psychological exercise program enhanced physical strength, activity of daily living, life satisfaction, and self‐esteem in older adults with hemiplegia who generally have lower quality of life. Therefore, physical and psychological exercise program needs to be considered as a beneficial rehabilitation program to improve the health related‐quality of life in this population.
Hemodynamic responses to cooling and warming during a continuous simulated hemorrhage ramp
Authors: Poh Paula Y. S. , Gagnon Daniel , Romero Steven A. , Convertino Victor A. , Crandall Craig G.
Published: November 2023

One in 10 deaths worldwide is caused by traumatic injury, and 30–40% of those trauma‐related deaths are due to hemorrhage. Currently, warming a hemorrhaging victim is the standard of care due to the adverse effects of combined hemorrhage and hypothermia on survival. However, heating can be detrimental to the maintenance of arterial pressure and cerebral perfusion during a continuous hypotensive challenge.

PURPOSE

To test the hypothesis that warming a normothermic individual during a continuous simulated hemorrhage ramp is harmful to the maintenance of arterial pressure and cerebral perfusion, while skin surface cooling is beneficial.

METHODS

Twelve men (mean ± SD: age, 29 ± 8 y; weight, 82 ± 16 kg) underwent a randomized crossover study performed over 3 separate days. Following 15 min of supine rest, 10 min of 30 mmHg of lower body negative pressure (LBNP) was applied to simulate a mild hemorrhagic challenge. With LBNP continuing, subjects were then exposed to mild whole‐body warming (WARM; mean skin temperature (Tsk): 36.4 ± 0.5°C), skin surface cooling (COOL; Tsk: 30.5 ± 0.9°C), or remained thermoneutral (NEUT; Tsk: 33.9 ± 0.6°C). Five min after the thermal provocation, a continuous LBNP ramp was applied at a rate of 5 mmHg·min−1 until pre‐syncope. Hemodynamic and thermal variables were measured continuously.

RESULTS

Neither average time to pre‐syncope (P = 0.14) nor the LBNP level at pre‐syncope (P = 0.09) were different between thermal conditions. However, mean arterial blood pressure was elevated (92 ± 11 mmHg; P = 0.01) during COOL across the LBNP period, relative to NEUT (83 ± 9 mmHg) and WARM (79 ± 11 mmHg) trials. Middle cerebral artery blood velocity decreased (26 ± 1 cm·sec−1; P < 0.001) to a similar extent from baseline to pre‐syncope, regardless of the thermal conditions applied.

CONCLUSIONS

Contrary to our hypothesis, WARM did not impair LBNP tolerance or cerebral blood flow velocity. Although COOL increased blood pressure during the LBNP ramp, LBNP tolerance and cerebral perfusion were not different relative to the NEUT or WARM trials. These data indicate that mild whole‐body warming of a continuously hemorrhaging victim is not detrimental to hemodynamic stability.

Support or Funding Information

Project funded by DOD‐W81XWH‐12‐1‐0152.
Effect of Four Weeks Whole‐Body Vibration Training on Bone Mineral Density and Bending Strength in Young Adults
Authors: Flores Jaime G , Liang Michael T , Metchkoff Tatiana G , Chen Elbert , Auslander Alexandra T , Rocha Jose
Published: November 2023

The objective of this study is to determine the effect of four weeks whole body vibration (WBV) training on bone mineral density (BMD) and bending strength in young adults. Physically active (non‐athlete) women and men (n=43, F=31), age 20 – 31 years, volunteered as study subjects. Subjects were randomly assigned to: 1) WBV training, 1 session/day, 20‐min each (G1, n=15, F=12), 2) WBV training, 2 sessions/day, 10‐min each (G2, n=16, F=12), and 3) no treatment control (CON, n=12, F=7). G1 performed 8 bouts of vibration exercise, once a day; and G2 performed 4 bouts of vibration exercise, twice a day with 1–2 hours resting period between the training sessions. Each bout of WBV training consisted of 2.5 min vibration exercise followed by 1 min rest for a total of 4 (G2) or 8 (G1) bouts. Both G1 and G2 performed WBV 3 sessions a week for 4 weeks. A vibration platform (DKN Technology, Alhambra, CA) with a vibration frequency = 40 Hz, and magnitude = 4 g was used for WBV training. The training subjects stood on a vibration platform with knees bent at 40° angle, and feet contacting the platform at shoulder width. The CON did not perform WBV training for the entire four weeks of study. All subjects completed two study outcome measurements (pre‐ and post‐test) which include: 1) BMD at the hip, lumbar spine L1–L4, forearm, lower leg, and whole body using a dual‐energy X‐ray absorptiometry (DXA‐Hologic‐QDR series, Bedford, MA, USA), and 2) bone bending stiffness of the tibia using a Mechanical Response Tissue Analyzer (NASA, Moffett Field, CA, USA). A Hip Strength Analysis (HSA) software was used to obtain bone strength parameters for femoral neck and proximal femoral shaft. Results for within group comparison show significant increase from baseline to week 4 in hip bone mineral content (BMC) (4.56%, p=0.004) and hip BMD (1.2%, p=0.02), and decrease in femoral shaft cross‐sectional moment of inertia (−6.8%, p =0.02). In conclusion, our results indicate that a four‐week WBV training regimen induced osteogenic adaptation on BMD and BMC at the hip, and femoral shaft bending strength in young adults.
Kidney Injury Marker‐1: A Potential Point‐of‐Care Biomarker of Heat Stress
Authors: Audet Gerald N , Ward Jermaine A , Dineen Shauna M , Cheuvront Samuel N , Leon Lisa R
Published: November 2023

Heat injury/stroke (HI/S) is a substantial threat to military operational readiness as well as athletic and occupational performance. There are currently no specific tests capable of delineating HI/S severity. The kidney has been implicated as one of the earliest sensors of heat stress. We hypothesized that kidney injury marker‐1 protein (KIM‐1) could be a novel biomarker in assessing heat stress severity during early stages of recovery. Both animal and human models were used in this study. 1) Conscious male mice (N=15) were heated passively until reaching a core temperature (Tc) of 42.7 °C. Mice were sacrificed at 3 time points‐ maximal core temperature (Tc,Max),and either ~3hrs (T3) or 24hrs post‐heating (24hr)‐ and kidneys were collected. 2) Conscious male rats (N=24) were passively heated to a Tc,Max of 41.9 °C. Rats were segmented into 3 severities (mild;MILD, moderate; MOD, severe; SEV) based on Tc, heart rate, and blood pressure during recovery and sacrificed at 24hrs for urine and kidney collection. 3) Human subjects (Male N= 9; Female N=3)were subjected to exercise (50% VO2,Max) in the heat (Ta40°C) and either A) subjected to fluid restriction(dehydration, HS‐D) or B) or allowed to hydrate (euhydration, HS‐E). Urine samples were collected before heat stress and ~2 hours post heating. All rodent samples were analyzed for KIM‐1 using an ELISA assay or a KIM‐1 point of care (POC) test (Bio‐assay works). Humanurine was analyzed for KIM‐1 on a bio‐plex assay. In mouse kidney, KIM‐1 was unchanged at Tc,Max, but increased at T3 (313% vs. Conm) and 24hrs (>5000% vs. Conm). In rat kidneys, KIM‐1 was increased in all groups and correlated with increasing severity (MILD 274%, MOD 352%, SEV 432% vs. Conr). In rat urine, there was a ~200% increase in KIM‐1 vs Conr, however there was no difference between severities. The POC test was able to detect increased KIM‐1 content in the rat urine (10.9 μg/mL vs 0.0 μg/mL Conr), but the test showed no differences between MILD(13.3 μg/mL) and MOD (9.0 μg/mL) (insufficient sample from SEV). In humans, HS‐D resulted in greater dehydration than HS‐E (HS‐D 3.8 ± 0.1 % vs HS‐E 0.9 ± 0.1%), with both groups showing elevated Tc (Tc,Max: HS‐D 39.1 ± 0.2 °C, HS‐E 38.6 ± 0.1 °C). After heat stress, human urine showed an 80% and 275% increase in KIM‐1in HS‐E and HS‐D vs baseline, respectively. This suggests that KIM‐1 is sensitive to heat stress and the associated dehydration, and may also be able to predict the overall severity of heat stress. Further, the KIM‐1 POC test may serve as a simple and rapid tool for diagnosing heat stress. Author views not official US Army or DoD policy.
Contribution of Satellite Cells to Skeletal Muscle Proteostasis during Advanced Age and Aerobic Exercise
Authors: Konopka Adam R. , Ehrlicher Sarah E. , Baeverstad Kathryn A. , Reid Justin , Peelor Fredrick F. , Confides Amy L. , Dupont‐Versteegden Esther E. , Miller Benjamin F. , Hamilton Karyn L.
Published: November 2023

We have shown that the maintenance of skeletal muscle proteostasis is a shared characteristic in several animal models of slowed aging. Loss of satellite cell activity with advancing age has been correlated to impaired skeletal muscle remodeling however emerging evidence suggests satellite cells may not be requisite in preventing age‐related changes in skeletal muscle. It remains to be determined how satellite cell recruitment influences protein turnover during advanced age and after exercise. We hypothesized that satellite cells will have a minimal contribution to skeletal muscle proteostasis during aging and exercise. To test this hypothesis, at 4 months of age Pax7CreER‐DTA mice were treated with vehicle or tamoxifen to deplete satellite cells. The gastrocnemius muscle was harvested from young (7–10 months old) and old (23–24 months old) mice. A subset of mice from both age and treatment groups had access to voluntary running wheels (exercised) for the last two months to provide a stimulus for satellite cell recruitment while the other mice remained ambulatory (non‐exercised). After an intial i.p. bolus, mice received 8% D2O in their drinking water during the last 6 weeks of each intervention to assess the integrated synthesis rates of skeletal muscle subcellular fractions and DNA. Skeletal muscle mitochondrial and collagen protein synthesis were lower in aged mice regardless of satellite cell content, which is consistent with the notion of age‐related impairments in mitochondrial biogenesis and extracellular matrix turnover. Compared to vehicle, tamoxifen treatment decreased mitochondrial and collagen synthesis in the young, non‐exercised group. Collagen synthesis remained lower in aged, exercised mice with no influence from satellite cells. Interestingly, when satellite cells were depleted, mitochondrial protein synthesis was elevated in the exercised group. Additional analysis regarding DNA synthesis is forthcoming and warranted to provide context for the novel relationship between satellite cell depletion and augmented mitochondrial biogenesis after exercise. Although the mechanisms linking satellite cell depletion to augmented mitochondrial biogenesis after exercise remain unknown, these data suggest in the absence of satellite cells the energetic stress of exercise may selectively increase mitochondrial protein synthesis. These findings are consistent with our previous studies that indicate energetic stress favors cellular resources to be allocated for maintaining existing cellular structures rather than cell proliferation.

Support or Funding Information

NIA Grants AG043721 to EEVD and AG042569 to BFM and KLH.
Chronic Binge Alcohol (CBA) Administration decreases miR‐206 in simian immunodeficiency virus (SIV)‐infected Macaques
Authors: Simon Liz , Molina Patricia E
Published: November 2023

Decreased skeletal muscle (SKM) mass and function remains a strong and consistent predictor of mortality among persons living with HIV/AIDS (PLWHA) and occurs at an earlier age among PLWHA compared to the general population. SKM dysfunction is also prevalent in individuals with alcohol use disorders (AUDs). Previously we showed that CBA accentuates SKM wasting in simian immunodeficiency virus (SIV) infected rhesus macaques and this is associated with enhanced myoinflammation, oxidative stress, ubiquitin proteasome proteolytic pathways, and decreased regenerative capacity of SKM progenitor cells. This study tested the hypothesis that CBA‐induced alterations in SKM microRNA (myomiR) expression may contributing to impaired SKM regeneration in SIV‐infected macaques. Daily CBA (blood alcohol levels ~50 mM) or sucrose (SUC) administration was initiated 3 months prior to intrarectal SIVmac251 inoculation and continued throughout the study period. Antiretroviral therapy (ART) or placebo was initiated 2.5 months after SIV infection and continued through the study period. Four treatment groups (SUC/SIV±ART and CBA/SIV±ART) were studied at endpoint (11 months post SIV inoculation). Primary myoblasts isolated from SKM samples from CBA/SIV/ART+/− showed decreased myotube formation, myonuclei fusion index, and myogenic gene expression compared to those derived from SUC/SIV macaques. This was associated with decreased SKM miR‐206 expression. Transfection of naïve macaque myoblasts with a miR‐206 inhibitor resulted in a significant decrease in myogenic enhancer factor 2C (MEF2C), and decreased differentiation of myoblasts, suggesting a critical role of miR‐206 in myogenesis in macaque myoblasts. Circulating plasma levels of miR‐206 were significantly decreased in CBA/SIV/ART+/− macaques, reflecting a similar pattern to that seen in SKM. These results suggest altered SKM myomiR expression as a likely mechanism for decreased regenerative capacity in SKM of CBA/SIV macaques, irrespective of ART. The parallel changes in SKM and circulating levels of miR‐206 suggest the possible use of plasma miR‐206 as an indicator of impaired regenerative capacity in SKM of PLWHA and is currently under investigation.

Support or Funding Information

The work was supported by National Institutes of Health (NIH) grants: P60 AA09803
Sarcolemma Wounding Activates Dynamin Dependent Endocytosis in Striated Muscle
Authors: Thorson Molly T. , McDade Joel R. , Michele Daniel E.
Published: November 2023

Rationale

Mutations in the protein dysferlin have been shown to result in Limb Girdle Muscular Dystrophy 2B and Myoshi Myopathy. In patients and mouse models lacking dysferlin, dysfunctional membrane repair compromises the muscle cells and leads to muscle degeneration and progressive muscle wasting. Preliminary data in our laboratory suggests that sarcolemmal wounding stimulates the endocytosis of dysferlin. Therefore, the objective of this study was to investigate the potential regulators of wound‐induced membrane transport. We hypothesized that the activity of dynamin, a GTPase that facilitates endocytosis, may be important for the activation of membrane trafficking following wounding and possibly important for the wound‐induced endocytosis of dysferlin.

Methods and Results

Much research in the field has focused on measuring membrane disruption by monitoring the uptake of the extracellular, lipophilic dye, FM1‐43. However, FM1‐43 can also be used as a measure of endocytosis. Therefore, we used FM1‐43 dye to track endocytosis in adult skeletal muscle fibers at rest and following acute sarcolemma disruption. We show that while dysferlin recruitment to the wound site is not dependent upon dynamin, initial FM1‐43 loading is completely dependent upon dynamin activity. Furthermore, dynamin inhibition significantly reduces wound‐induced FM1‐43 uptake, suggesting that wound‐induced uptake occurs via dynamin‐dependent endocytosis. We show, in agreement with others, that dysferlin‐deficient muscle fibers show elevated FM1‐43 uptake following wounding, which is the basis for the assertion that membrane repair is defective in this model. However, our data suggest that the upregulation of wound‐induced endocytosis may contribute to the increased uptake of FM1‐43 following wounding in dysferlin‐deficient muscle fibers.

Conclusions

These data highlight a previously unappreciated role for dynamin‐dependent endocytosis in resting and wounded adult skeletal muscle fibers. Importantly, FM1‐43 uptake following wounding is considered to be the “gold standard” for membrane repair studies in muscle. However, these data also suggest FM1‐43 uptake following wounding may reflect wound‐induced endocytosis, in addition to local influx of dye at the wound. Research in our laboratory is exploring the use of other methods of measuring membrane repair in order to distinguish the process of wound‐induced endocytosis from local re‐sealing of the wound site itself.

Support or Funding Information

This work has been supported by the American Heart Association (#12PRE12050130) to JM, the NIH Cellular and Molecular Biology Training Grant T‐32‐GM007315 to MT and NIH NIAMS AR066213 to DM.