bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Regulation of Cardiac Substrate Utilization in Response to Chronic Central Nervous System Administration of Leptin and Melanotan II in Rats with Myocardial Infarction
Authors: da Silva Alexandre A. , Harmancey Romain , Dai Xuemei , Moak Sydney P. , Roy Cary N. , Wang Zhen , Hall John E. , do Carmo Jussara M. 
Published: June 2021

The brain leptin‐melanocortin system pathway plays an important role in regulating many physiological functions including energy homeostasis. We found that chronic intracerebroventricular (ICV) infusion of leptin or the melanocortin 4 receptor (MC4R) agonist Melanotan II, MTII, markedly attenuated cardiac dysfunction in rats with myocardial infarction (MI) induced by permanent left anterior descending coronary artery (LAD) ligation. In the present study we examined if activation of leptin‐MC4R axis in the central nervous system (CNS) alters cardiac substrate utilization in rats with MI. Male Sprague‐Dawley rats at 15 weeks of age were implanted with an ICV cannula into the lateral ventricle. After 10 days of recovery, the LAD was permanently ligated and saline vehicle (0.5 μL/hr, n=5), leptin (15 μg/day, n=5) or MTII (240 ng/day, n=3) was infused ICV via osmotic minipump for 14 consecutive days. On day 14 of treatment the hearts were quickly excised and perfused ex vivo in the working mode with glucose (5.5 mmol/L) and the fatty acid oleate (0.4 mmol/L). After a 5‐min baseline equilibration period the hearts were perfused for an additional 20 min and coronary flow samples were collected every 5 min to determine rates of substrate oxidation by quantitative measurement of [14C]O2 and [3H]2O using [U‐14C]glucose (0.08 μCi/ml) and [9,10‐3H]oleate (0.1 μCi/ml) as the radiolabeled tracers. Compared to vehicle treatment, chronic ICV leptin infusion for 2 weeks markedly increased glucose oxidation (0.60±0.04 vs. 0.27±0.02 μmol/min/g dry heart weight) without altering oleate oxidation (0.95±0.01 vs. 0.90±0.02 μmol/min/g dry heart weight). Chronic central MTII infusion did not alter glucose oxidation (0.25±0.03 vs. 0.27±0.02 μmol/min/g dry heart weight) but increased fatty acid oxidation compared to vehicle treatment (1.13±0.01 vs. 0.90±0.02 μmol/min/g dry heart weight). These results suggest the CNSmechanisms by which leptin and MC4R activation improve cardiac function post MI may involve increased myocardial bioenergetics by differential modulation of glucose and fatty acid utilization.Support or Funding InformationNHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chemotherapy acutely impairs neurovascular and hemodynamic responses in patients with breast cancer
Authors: Sales Allan Kluser , Negrao Marcelo , Testa Laura , Ferreira‐Santos Larissa , Groehs Raphaela , Carvalho Bruna , Toschi‐Dias Edgar , Rocha Natalia , Laurindo Francisco , Debbas Victor Kluser , Rondon Maria Kluser , Mano Max , Hajjar Ludhmila , Hoff Paulo , Filho Robero , Negrao Carlos 
Published: June 2021

PurposeThe purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in patients with breast cancer.MethodsSixteen women (age: 47.0±2.0 years; body mass index: 24.2±1.5 Kg.m−2) with stage II–III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600mg/m2) were administered in 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA, microneurography), calf blood flow (CBF, plethysmography) and calf vascular conductance (CVC), heart rate (HR, electrocardiography) and beat‐to‐beat blood pressure (BP) (Finger plethysmography) were measured before, during and after each session. Blood samples (5 mL) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs, flow cytometry), a surrogate marker for endothelial damage.ResultsMSNA and BP responses were increased (P<0.001), whereas CBF and CVC responses were decreased (P<0.001), during and after CHT session when compared to SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMPs response to CHT (P=0.03 vs. SL session). No difference in HR response was observed (p>0.05).ConclusionsAdjuvant CHT with DX and CY in patients treated for breast cancer leads to acute sympathetic hyperactivity and endothelial alterations, which results in reduced muscle vascular conductance and elevated systemic BP. These responses may anticipate susceptibility to CHT‐induced longterm cardiovascular alterations.Support or Funding InformationSão Paulo Research Foundation ‐ FAPESPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Epidural spinal cord stimulation for neuropathic pain reduces blood pressure in patients with hypertension independent of pain relief: A retrospective study
Authors: Holwerda Seth W. , Holland Marshall T. , Green Alex L. , Collins Michael T. , Pearson Amy C. , Pierce Gary L. 
Published: June 2021

Evidence suggests that epidural spinal cord stimulation (SCS) reduces peripheral sympathetic outflow in patients treated for peripheral artery disease and neuropathic pain. However, the extent to which SCS reduces arterial blood pressure (BP) has received little attention. We tested the hypothesis that systolic BP (SBP) would be reduced in patients with hypertension (HTN) receiving surgically implanted SCS for management of neuropathic pain, and that SBP reduction would be independent of reduced neuropathic pain. Retrospective analysis of daytime SBP from patient medical records at the University of Iowa was performed from 2008 to 2018, and event‐triggered averaging was used to determine 2‐year SBP averages prior to SCS implant (pre‐SCS) and 2‐year SBP averages after SCS implant (SCS) in stage 1 HTN (n=170) and stage 2 HTN (n=141) patients. SCS SBP was significantly lower compared with pre‐SCS SBP (Pre‐SCS: 140±1 vs. SCS: 134±1 mmHg, P<0.001), and the reduction was greater in stage 2 HTN compared with stage 1 HTN (Stage 2: −11±1 vs. Stage 1: −2±1 mmHg, P<0.001), while reduction in neuropathic pain (scale 1–10) was not significantly different between groups (Stage 2: −1.4±0.3 vs. Stage 1: −1.1±0.2, P=0.37). Reduction in SBP following SCS was significantly greater in HTN patients on anti‐HTN medications compared with no anti‐HTN medications (Meds: −9±2 vs. No meds: −5±1 mmHg, P=0.036). The reduction in SBP following SCS was significantly correlated with higher Pre‐SCS SBP after controlling for sex, age, number of anti‐HTN medications, and reduction in neuropathic pain (R=−0.42, P<0.001). These findings suggest that SCS treatment for neuropathic pain in patients with HTN reduces BP independent of reductions in pain, and that the reduction in BP may be potentiated by anti‐HTN medications.Support or Funding InformationAHA (17POST33440101), T32 HL07121, NHLBI (P01HL014388), U54 TR001356 and AHA (13DG143400012)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dynamic and Static Handgrip Exercise Increase Wave Reflection in Healthy Young Adults
Authors: Stock Joseph M , Chouramanis Nicholas V , Chirinos Julio A , Edwards David G 
Published: June 2021

Increased wave reflection augments pulsatile load, wastes left ventricular effort, and is associated with cardiovascular events. Acute handgrip (HG) exercise increases central blood pressure and surrogate measure of wave reflection, augmentation index. However, surrogate measures of wave reflection do not provide a comprehensive assessment of pulsatile load and ventricular‐arterial interactions. Wave separation analysis can determine the relative contributions of forward (Pf) and backward (Pb) pressure wave amplitudes and reflection magnitude (RM=Pb/Pf) as well as the timing of apparent wave reflection return.PURPOSETo determine the effect of acute dynamic and static HG exercise on wave reflection magnitude and timing with wave separation analysis in young healthy adults.METHODSApplanation tonometry was used to record radial artery pressure waveforms in 31 adults (25±4 years) at baseline and during dynamic and static HG exercise in randomized order. Radial waves were calibrated to respective brachial mean and diastolic pressures and synthesized to central pressure waves using a generalized transfer function. Wave separation analysis was used to derive Pf, Pb, RM, and reflected wave transit time which was performed offline using a synthesized flow waveform.RESULTSCentral blood pressure and augmentation index increased with HG exercise as expected (p<0.05). Compared to baseline, both HG exercises increased wave reflection measures Pb (baseline 11.4±0.4 mmHg; dynamic 12.6±0.5 mmHg; static 12.7±0.6 mmHg, p<0.05) and RM (baseline 40±1%; dynamic 43±1%; static 44±1%, p<0.05), but not Pf (baseline 28.4±1.1 mmHg; dynamic 29.1±1.2 mmHg; static 28.8±1.2 mmHg, p>0.05). Reflected wave transit time was shortened with static but not dynamic HG exercise compared to baseline (baseline 95±4 ms; dynamic 90±3 ms; static 83±3 ms, p<0.05)CONCLUSIONBoth HG exercises increased measures of wave reflection (Pb and RM) suggesting greater wave reflection during HG exercise.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Autonomic Nervous System and its Relevance in the Regulation of Heart Rate Recovery Post Exercise
Authors: Leon‐Ariza Henry Humberto , Botero‐Rosas Daniel Alfonso , Reyes‐Cruz Dario , Dussan‐Trujillo Maria Margarita , Maldonado‐Arango Maria Ines , Pulido‐Cardozo Laura Ximena , Zea‐Robles Aura Catalina 
Published: June 2021

The recording of heart rate variability (HRV) is a strategy for the rapid and non‐invasive evaluation of the Autonomic Nervous System (ANS) activity. Previous studies have shown a rapid activation of the parasympathetic nervous system at the end of a physical effort and the association of this with the likelihood of developing cardiovascular disease.PURPOSEEstablish the relationship between recovery heart rate (RHR) after exercise and HRV at rest in apparently healthy men and women.METHODSQuantitative, cross‐sectional, exploratory research conducted in 50 subjects (25 men and 25 women) of 19 ± 2.34 years. Subjects were monitored by continuous electrocardiographic reading all throughout the different activities. The HRV was evaluated at rest for 5 minutes, using time, frequency and non‐linear analyzes, cardiac vagal index (CVI) was calculated using Log10 (SD1*SD2). Subsequently, a physical test of 6 minutes on the bike was performed between 50 and 60% of the maximum reserve heart rate. In the end, the RHR was evaluated every 10 seconds during the first minute. Subsequently, the relationship between HRV and RHR was analyzed using the Pearson correlation coefficient (r).RESULTSIn all population, mean HR at rest and RHR had an inverse effect, finding the following correlations: 10s (r = −0.35 p = 0.01), 20s (r = −0.37 p = 0.007), 40s (r = −0.40 p = 0.004) and 60s (r = −0.53 p = 0.000). Additionally, in women exist a direct correlation between RHR and CVI been more significant in the following correlations: 40s (r = 0.41 p= 0.044), 50s (r = 0.52 p= 0.008) and 60s (r = 0.59 p = 0.002); however, in men this correlation was not significant.CONCLUSIONSWhen performing stress tests in apparently healthy people, the decrease of the HR after exercise could be used to evaluate the activity of the ANS, specifically the activation of parasympathetic system demonstrated by the significant correlations between RHR and HR at rest, as well as the correlation between RHR and CVI. Therefore, the activity in the first minute after ceasing the exercise shows that the evaluation of the parasympathetic nervous system could be implemented in the early diagnosis and prognosis of chronic diseases including cardiovascular disease.Support or Funding InformationThe research was funding by the Faculty of Medicine of the Universidad La Sabana with the support of PROSEIM research group.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Validity of Stroke Volume and Cardiac Output Measurement between Finger Photoplethysmography and Continuous Wave Echocardiography during Treadmill Exercise in Adults with and without Down syndrome
Authors: Hibner Brooks A , Hilgenkamp Thessa I.M. , Schroeder Elizabeth C. , Lefferts Wesley K. , Fernhall Bo 
Published: June 2021

Individuals with Down Syndrome (DS) have decreased aerobic capacity (VO2peak) and blunted fitness improvements with exercise training. Both decreased capacity and limited change is likely explained by autonomic dysfunction resulting in chronotropic incompetence. Increased stroke volume could potentially compensate for blunted heart rate increases and maintain cardiac output, however it is unknown if this occurs in those with DS. Therefore, it is important to accurately measure SV and Q during exercise to further evaluate limitations to peak aerobic capacity within this population. Stroke volume (SV) and cardiac output (Q) can be non‐invasively assessed during exercise via finger photoplethysmography (PPG) however this has not been validated in DS.PURPOSEDetermine the concurrent validity of PPG, using continuous wave echocardiography (CWE) as the standard method, during exercise in adults with and without DS (control).METHODSAdults with DS (n= 6, 25 ± 2 yrs, 31.7 ± 4.6 kg/m2, 24.2 ± 4.2 ml/kg/min) and without DS (n= 5, 26 ± 4 yrs, 24.9 ± 4.8 kg/m2, 32.5 ± 6.4 ml/kg/min) performed a maximal incremental treadmill test to assess VO2peak. CWE images were captured at baseline, at each 2 minute exercise stage for 10 minutes and during recovery. PPG measurements were continuously obtained and then averaged over the last 30 seconds, matching CWE capture time points. Mean difference of combined time points between CWE and PPG was analyzed with t‐test and intraclass correlation coefficients (ICC absolute agreement) were computed between measurement methods for SV and Q. Validity based on ICC is considered poor: < 0.4, moderate: 0.5 – 0.75, or good: >0.75.RESULTSMean difference (CWE‐PPG) between measurement methods in both SV and Q in controls was significantly different from zero (SV: −13.5 ± 23.86 ml p <0.01 and Q: −1.9 ± 2.9 L/min p <0.01) while no difference were evident in those with DS (SV: 0.7 ± 31.6 ml p =0.86 and Q: −0.4 ± 3.3 L/min p =0.33) The overall ICC for SV and Q was 0.543 and 0.712, respectively. Once separated by group, the ICC for SV in the control group was 0.760 and the DS group was 0.128. ICC between Q measures in control was 0.773 and in DS was 0.646.CONCLUSIONAlthough PPG and CWE showed sufficient agreement between both SV and Q in individuals without DS, the absolute means were significantly different between methods. In individuals with DS, agreement between methods was low and moderate for SV and Q respectively, although the absolute means were not significantly different. Since the concurrent validity with CWE is not sufficient for PPG, we therefore recommend stroke volume measurement be obtained with CWE.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fasting and Postprandial Trimethylamine N‐oxide in Sedentary and Endurance Trained Males
Authors: Steele Cortney , Baugh Mary Elizabeth , Griffin Laura , Neilson Andrew , Davy Brenda , Hulver Matthew , Davy Kevin 
Published: June 2021

BackgroundGut bacteria release trimethylamine (TMA) from dietary substrates, e.g., choline, phosphatidylcholine, and L‐carnitine. TMA is absorbed and subsequently oxidized in the liver to produce trimethylamine N‐oxide (TMAO). TMAO is associated with type 2 diabetes (T2D) and increased risk of cardiovascular disease. Consumption of a high fat diet (HFD) is associated with increase in TMAO in sedentary individuals. However, whether the increase in TMAO with consumption in a HFD is observed in endurance trained individuals is unknown.MethodsHealthy, sedentary (n=17) and endurance trained (n=7) males consumed a 10‐day isocaloric lead‐in diet comprised of 55% carbohydrate, 30% total fat, <10% saturated fat prior to baseline testing. Blood samples were obtained in the fasting state and every hour during a 4‐hour high fat challenge (HFC) meal (820 kcal; 25% carbohydrate, 63% fat [21% saturated fat]) at baseline and following 5‐day HFD (30% carbohydrate, 55% total fat, 25% saturated fat). Plasma TMAO and TMA‐moieties (choline, betaine, L‐carnitine) were measured using isocratic ultraperformance liquid chromatography‐tandem mass spectrometry.ResultsAge (23±3 vs. 22±2.1 yrs) and body mass index (23.4± 3.0 vs. 23.5±2.1 kg/m2) were similar (both P>0.05) in the sedentary and endurance trained group, respectively. As expected, VO2max was significantly higher in the endurance trained compared with sedentary individuals (56.7±8.2 vs. 39.3±5.8 ml/kg/min). There were no significant differences in fasting (1.92 ± 0.8 μM vs. 2.09 ± 1.1 μM, P>0.05) or postprandial TMAO between sedentary or trained individuals, respectively, at baseline. Neither fasting (1.49± 1.2 μM vs. 2.25 ± 1.4 μM, P>0.05) or postprandial TMAO changed significantly with the HFD in the sedentary and endurance training individuals.ConclusionsNeither fasting nor postprandial TMAO changed significantly following the HFD in the endurance trained compared to sedentary individuals in the present study. Future studies are needed to identify effective interventions that target TMA‐releasing bacteria and reduce TMAO.Support or Funding InformationAmerican Diabetes Association and Translation Obesity Research Interdisciplinary Graduate Education ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Age does not increase muscle fatigue resistance of the diaphragm
Authors: Fogarty Matthew J. , Mantilla Carlos B. , Sieck Gary C. 
Published: June 2021

The diaphragm muscle (DIAm) comprises a mixed population of motor units, with FInt and FF units (type IIx and/or IIb fibers) vulnerable to sarcopenia ‐ age‐associated reductions of specific force and cross‐sectional area (CSA). Fatigue‐resistant S and FR units (type I and IIa fibers) are relatively spared. There is controversy as to whether aging confers an enhanced resistance to DIAm fatigue, with interpretations relying on relative measurements of force. We assessed the loss of DIAm force in 6‐ and 24‐month old Fischer 344 rats at 10, 40 and 75 Hz stimulation in 330 ms duration trains repeated each s (33% duty cycle) across a 2 min period. Although the initial specific force of the DIAm was lower in older rats across all stimulation frequencies, the final residual DIAm specific force after 2 min of stimulation was the same (~5 N/cm2) at all ages. This gave the misconception of an improved fatigue resistance, especially at 40 and 75 Hz. We also found that aging is associated with an increase in the relative contributions of type I and IIa fiber CSA to DIAm mass with decreased contributions of type IIx and/or IIb fibers. When these changing contributions are factored into a fiber type‐specific model of DIAm force generation, we found that ventilatory behaviors require activation of only type I and IIa fibers, regardless of age or fatigue. By contrast, the model predicts that aging impairs the ability of the DIAm to effectively perform expulsive manoeuvres, even in the non‐fatigued condition. In summary, relative fatigue measurements are not indicative of improved fatigue resistance in aging and are an artifact of reduced initial specific force contributions from FInt and FF units. These results are consistent with previous studies showing the relative vulnerability of FInt and FF units and conserved ventilatory behaviors in aging DIAm.Support or Funding InformationR01‐AG044615This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nitric oxide dependent delay in post‐fatigue contractile recovery in isolated fast‐twitch muscle: The role of the S‐nitrosoglutathione reductase
Authors: Gilmore Natalie K , Hogan Micheal C , Nogueira Leonardo 
Published: June 2021

During fatiguing contractions, skeletal muscle fibers produce nitric oxide (NO) (and possibly S‐nitrosoglutathione (GSNO)) due to the activation of calcium‐calmodulin dependent NO‐synthases (NOS). Myofibers contain GSNO reductase (GSNOR), an enzyme that consumes GSNO, thereby controlling intracellular protein S‐nitrosylation. The present investigation tested the hypothesis that GSNOR scavenges the GSNO produced during repetitive contractions to protect contractile and calcium handling proteins from being S‐nitrosylated. To test this hypothesis, the effects of acute inhibition of GSNOR (GSNORi; SPL‐334, 10 μM) on contractility during and after fatiguing contractions in fast‐twitch muscle were examined. Extensor digitorum longus (EDL) muscles from both hindlimbs of mice (C57BL6/J; 8–9 weeks old) were dissected and placed in an experimental chamber for ex‐vivo isometric force measurements during electrical stimulation. For each mouse, one EDL was treated with the GSNORi, or L‐NMMA (L‐N‐monomethyl Arginine, a NOS inhibitor; 400 μM), or both, while the other EDL served as an untreated control. Muscles were repetitively stimulated at increasing frequencies until force was decreased to 30% of initial force. Contractile recovery from fatigue was determined at submaximal and maximal frequencies of stimulation for 120 min post‐fatigue. The treatment with either GSNORi or L‐NMMA did not change maximal or submaximal force development. Acute GSNORi incubation significantly decreased the force development during fatiguing contractions (~30% less force) compared to untreated muscles. During muscle recovery from fatigue in the untreated control muscle, force developed at low frequencies of stimulation was ~80% of pre‐fatigue values after 120 min of recovery. However, when GSNORi was present during fatigue and during recovery post‐fatigue, the force developed at submaximal and maximal frequencies of stimulation were both significantly impaired compared to control (to 55–70% of pre‐fatigue values after 120 min, P<0.05 vs control). The NO‐dependent effects of GSNORi incubation on post‐fatigue recovery were tested when L‐NMMA was present to block NO production. L‐NMMA completely abolished the delayed contractile recovery detected with GSNORi. These data suggest that fatiguing contractions increase NO production thereby enhancing the intracellular amounts of GSNO, which can negatively affect muscle recovery post‐fatigue when GSNOR is inhibited. These results indicate that GSNOR activity has an important role in protecting contractile function during stimulation patterns that lead to muscle fatigue.Support or Funding InformationNIH (AR069577), CNPq (Universal)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.