bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoreflexes : A Major Component of Adaptation to High Altitude/Hypoxic Environment
Authors: Richalet Jean‐Paul , Voituron Nicolas , Hermand Eric , Jeton Florine , Lhuissier François J 
Published: November 2023

The decrease in O2 pressure in hypoxia, either at high altitude or in disease, induces physiological responses mediated through oxygen sensing systems. Among those responses, chemoreflexes play a major role, especially during the initial phase of exposure to hypoxia. Peripheral chemoreceptors (carotid bodies) and central receptors (retrotrapezoid nucleus) are sensitive to hypoxia and hypercapnia and modulate the activity of the Respiratory rhythm generator. Our aim was to determine the role of erythropoietin (Epo) on those mechanisms in two animal models: transgenic anemic mice under‐expressing Epo (EpoTagh), and the Pika (Ochotona curzoniae) a lagomorph genetically adapted to high altitude on the Tibetan plateau. We showed that Epo are necessary for ventilatory acclimatization in EpoTagh mice and that nNOS and NMDA receptors are overexpressed in the medulla of Pikas. In humans, the sensitivity to hypoxia is a determinant factor for acclimatization to high altitude. A prospective cohort study on 1017 subjects has shown that the ventilatory response to hypoxia at exercise is predictive of the occurrence of severe high altitude illnesses (SHAI). From clinical evaluation and physiological response to hypoxia measured during a hypoxia exercise test, a predictive score of SHAI was calculated, which allowed the detection of high‐risk subjects. Instability of the control of ventilation has been evidenced during exercise in hypoxia, with oscillations of ventilation with a period of 11–12 seconds. The mechanisms of this instability is linked to the gain of the O2 and CO2 response, as well as other factors such as dead space and cardiac output.Support or Funding InformationLaboratory of Excellence GrEx
Cerebral and peripheral circulation and progression of Alzheimer's disease
Authors: Pedrinolla Anna , Venturelli Massimo , Fonte Cristina , Galazzo Ilaria Boscolo , Crispoltoni Lucia , Benetti Maria Vittoria , Stabile Anna , Pistilli Alessandra , Rende Mario , Pizzini Fracesca Benedetta , Smania Nicola , Schena Federico 
Published: November 2023

BackgroundIn aging, cerebral and systemic circulation decline likewise to cognitive decline. Also, reduced availability of nitric oxide (NO) in both cerebral and peripheral blood vessels results in further alterations of circulation. Therefore, changes in circulation and NO availability may contribute to the development of Alzheimer's disease (AD). However, current literature lacks of evidence about the progression of AD and circulation impairment at both cerebral and peripheral level.AimsFirst aim of the study was to verify if circulation at cerebral and peripheral level is significantly reduced in AD patients compared with age‐matched healthy counterparts. Second aim was to verify if circulation at cerebral and peripheral level declines further with the severity of AD. Potential correlation between circulation and NO availability was also assessed.MethodsIn 55 AD patients (severity of dementia distribution: 12 MCI, 15 AD1, 19 AD2, 9 AD3), 13 healthy elderly (OLD), and 10 young (YG) subjects, cerebral blood flow (CBF) with partial volume correction, blood flow of carotid (CB) and femoral (FB) arteries were assessed. In addition, systemic vascular function was assessed by means of passive limb movement (PLM). NO availability was determined via plasma NO metabolites (NO−3 +NO−2).ResultsCBF was 57 ml/min/100gr, 48.6 ml/min/100gr, 44 ml/min/100gr, 40 ml/min/100gr, 34 ml/min/100gr, 30 ml/min/100gr in YG, OLD, MCI, AD1, AD2, and AD3 respectively. CF was 613 ml/min, 535 ml/min, 479 ml/min, 450 ml/min, 348 ml/min, 309 ml/min in YG, OLD, MCI, AD1, AD2, and AD3 respectively. FB was 403 l/min, 325 ml/min, 288 ml/min, 253 ml/min, 224 ml/min in YG, OLD, MCI, AD1, AD2, and AD3 respectively. Δpeak PLM was 739 ml/min, 284 ml/min, 227, 182 ml/min, 166 ml/min, 155 ml/min in YG, OLD, MCI, AD1, AD2, and AD3 respectively. NO−3 +NO−2 was 53 μM, 47 μM, 42 μM, 40 μM, 38 μM, 35 μM in YG, OLD, MCI, AD1, AD2, and AD3 respectively. Correlation between CBF and Δpeak PLM was r=0.677 (p<.01). Correlation between Δpeak PLM and NO−3+NO−2 was r=0.9765 (p<.01).ConclusionOur results confirm that CBF as well as CB, FB, Δpeak PLM and NO−3 +NO−2 are reduced in aging. AD patients exhibited a further reduction of all these parameters compared with healthy age‐matched counterparts. Moreover, circulation and NO availability were progressively declined with the progression of dementia, implicating that AD and its progression might be the result of an intertwined decline of both neural and vascular functions, likely related to the NO availability.Support or Funding InformationNo funding was received.
Exercise Ameliorated Cognitive Dysfunction through Mitochondrial Remodeling in Alcohol Administrated C57BL/6 Mice
Authors: Kelly Kimberly E. , George Akash K. , Behera Jyotirmaya , Tyagi Neetu 
Published: November 2023

Alcohol consumption is a potent inducer of oxidative stress. Previous data indicate that alcohol consumption induces mitochondrial dysfunction and free radical production in mouse cerebral cortex. Exercise has been recommended by clinicians as a secondary protective therapy; however, its effect on brain functions through mitochondrial interventions has not been fully explored. Therefore, we hypothesized that exercise mitigates alcohol‐induced neurodegeneration and decline in cognitive function through mitochondrial remodeling. To test this hypothesis, we selected 10–12 weeks old male wild‐type mice (C57BL/6, WT), grouped as follows: 1) WT, 2) WT+ Alcohol, 3) WT+ Exercise, 4) WT+ Alcohol+ Exercise. Mice were given an intraperitoneal injection of EtOH (1.5g/kg BW) or saline solution every day for 12 weeks. The mice were exercised for 12 weeks on a treadmill with a controlled speed of 7 meters/min for the first week, the speed of 10 meters/min for the second week and 11 meters/min in the following weeks and a total of 330 meters every day. After each 110 meters mice were given rest of 10 minutes. Cognitive and behavior alterations were assessed by Novel Object Recognition, Passive Avoidance, and Y‐maze tests. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Our results suggest significant improvement in cognitive functions in exercised alcohol administrated group, as compared to non‐exercised alcohol administrated group. The involvement of mitochondrial remodeling in mice following exercise was further confirmed and we found there was a significant increase in ATP production, membrane potential, oxygen consumption, copy‐number as well as a decrease in reactive oxygen species when compared with non‐exercised alcoholic mice. Furthermore, a considerable reduction in TUNEL reactivity was determined in intact mitochondria isolated from the exercised group as compared to non‐exercised alcoholic mice. In addition, the effect of exercise on neuronal survival in the alcoholic brain was confirmed by Fluoro‐Jade C reactivity. Taken together, our results indicate a myriad of beneficiary effects of exercise over mitochondrial pathology during alcoholism. Furthermore, our findings suggest exercise mitigates neurodegeneration and cognitive dysfunction and thereby improving total mitochondrial function.Support or Funding InformationThis work was supported by NIH grant HL107640‐NT.
The dipeptidyl peptidase IV inhibitor saxagliptin prevents angiotensin II‐induced cardiac diastolic dysfunction: potential involvement of cardiac lymphocytes?
Authors: Brown Scott M , Smith Cassandra E , Khan Maloree , Meuth Alex I , Sowers James R , Chandrasekar Bysani , DeMarco Vincent G , Nistala Ravi , Bender Shawn B 
Published: November 2023

Activation of the renin‐angiotensin‐aldosterone system (RAAS) is common in subjects with obesity, insulin resistance, and cardiovascular dysfunction. Recently, the anti‐hyperglycemia drugs dipeptidyl peptidase‐IV (DPPIV) inhibitors have been shown to exert cardioprotective effects in these patients; however, the impact of DPPIV inhibition on RAAS‐dependent cardiac injury and the underlying molecular mechanisms have not been investigated. Here, we hypothesized that DPPIV inhibition with saxagliptin (Saxa) attenuates angiotensin II (Ang II)‐induced cardiac dysfunction. Male C57BL/6J mice (13 weeks of age) underwent Ang II (sc, 500 ng/kg/min) or vehicle infusion for 3 wks. Animals received Saxa (po, 10 mg/kg/d) or placebo during the final 2 weeks of Ang II infusion. Echocardiography revealed diastolic dysfunction with Ang II infusion, indicated by reduced E′/A′ ratio, coincident with aortic stiffening (i.e., increased pulse wave velocity). Further, Ang II induced cardiac hypertrophy and periarterial, but not interstitial, fibrosis. Ang II also increased pro‐fibrotic (collagen I, CTGF), oxidative stress (NOX2), and macrophage‐specific (CD11c, CD163, CD86) gene expression. In fact, flow cytometry revealed increased CD45+F4/80+CD11b+ macrophages and a tendency for increased CD45+CD4+ lymphocytes in the heart. Treatment with Saxa significantly reduced plasma DPPIV activity by ~60% and abrogated Ang II‐induced cardiac diastolic dysfunction, but not aortic stiffening. Moreover, Saxa inhibited Ang II‐induced upregulation of cardiac Collagen 1 gene expression and periarterial fibrosis. Interestingly, Saxa failed to modulate the hypertrophic response. Saxa also failed to alter cardiac CD45+F4/80+CD11b+ macrophage recruitment. It did however elevate cardiac memory/effector CD45+CD8+CD44+ lymphocytes. Taken together, these results demonstrate that DPPIV inhibition with Saxa can prevent Ang II‐induced cardiac fibrosis and diastolic dysfunction. Furthermore, the benefit of Saxa treatment may involve a recently described anti‐fibrotic role of memory/effector CD8+ lymphocytes. DPPIV inhibition with Saxa may therefore represent a novel therapeutic approach for cardiac diastolic dysfunction in states associated with RAAS activation.Support or Funding InformationSupported by funding from AstraZeneca (SBB and RN) and VA BLR&D CDA‐2 BX002030 (SBB).
Assessing cardiac function during simulated activities of daily living: A magnetic resonance imaging study
Authors: Beaudry Rhys I , Samuel Thomas J , Tucker Wesley , Zaha Vlad G , Singhavi Monika , Haykowsky Mark J , Nelson Michael D 
Published: November 2023

Cardiac magnetic resonance imaging (cMRI) is the clinical gold‐standard imaging tool for evaluation of left ventricular morphology and function. Increasing cardiac demand through stress testing improves prognostic value of cardiac imaging; however, current MR stress testing approaches remain limited to pharmaceutical agents (e.g. dobutamine, adenosine) which only partially mimic the metabolic demands of activities of daily living. With the advent of MR‐compatible exercise equipment, we can now simulate the metabolic cost associated with activities of daily living during a single standardized cMRI exam. To demonstrate this, we first established the association between supine work rate and metabolic equivalents (METs) in ten healthy subjects (age: 25 ± 4 years; female/male: 5/5; BMI: 22.8 ± 3.2 kg/m2). We used four incremental workloads on a commercially available, MR compatible leg ergometer (Ergospect, Tirol, Austria), at a cadence of 60 steps per minute until steady state VO2 and measured METs using expired gas analysis (ParvoMedics TrueOne 2400). We then examined left ventricular volumes and global systolic function by cMRI in 6 subjects (age: 23 ± 1 years; female/male: 3/3; BMI: 25.5 ± 3.7 kg/m2) at rest, and at a workload equivalent to 3 METS—near the minimum threshold for independent living—using standardized, vendor provided, imaging sequences (GE Healthcare, Waukesha, Wisconsin, USA). As expected, heart rate increased significantly with exercise (67 ± 10 bpm rest vs. 122 ± 7 bpm 3 METS, p<0.05). LV end‐diastolic volumes, normalized to body surface area (BSA), decreased with exercise (80.2 ± 17.4 ml/m2 rest vs. 63.9 ± 24.8 ml/m2 3 METS), in parallel with reductions in end‐systolic volumes/BSA (26.6 ± 8.9 ml/m2 rest vs. 18.6 ± 8.7 ml/m2 3 METS). A slight decrease in stroke volume (51.1 ± 11.4 ml/m2 rest vs. 45.2 ± 18.7 ml/m2 3 METS) coupled with the drop in end‐diastolic volume preserved ejection fraction during exercise (67 ± 8% rest vs. 71 ± 6% 3 METS), and increased cardiac output (Δcardiac output: 1.3 ± 1.1 l/min/m2, 24 ± 19%). Taken together, these preliminary data demonstrate our ability assess the cardiac functional reserve required for activities of daily living using cMRI. More work is needed to include regional measures of myocardial tissue deformation, and to extend this work to clinical populations.Support or Funding InformationThis work was supported by AHA 16SDG27260115 and the Harry S. Moss Heart Trust.
Cervicothoracic Transcutaneous Electrical Nerve Stimulation Attenuates Cardiac Sympathetic Overdrive in Heart Failure: A 123l‐MIBG Myocardial Scintigraphy, Randomized Double‐Blind Crossover Trial
Authors: Fernandes Igor Alexandre , Campos Monique Opuszcka , Miranda Sandra Marina , Ribeiro Mario Claudio Lucas , Braghiroll Ana Maria Silveira , Mesquita Claudio Tinoco , Nóbrega Antonio Claudio Lucas 
Published: November 2023

IntroductionCardiac sympathetic drive provides inotropic support to the failing heart and preserves cardiovascular homeostasis. Nonetheless, as myocardial insult evolves, this compensatory response leads to a progressive decline in contractile function, increases the vulnerability to arrhythmias and constitutes an independent mortality predictor. Despite advanced pharmacological therapies, side effects and persistent cardiac sympathetic overdrive highlights the modulation of the adrenergic system as a primary target for non‐pharmacological strategies in the heart failure (HF) treatment. In this scenario, we propose cervicothoracic transcutaneous electrical nerve stimulation (TENS) as a non‐pharmacological therapy to attenuate cardiac sympathetic overdrive in patients with heart failure.MethodsIn this prospective, randomized, sham‐controlled, double‐blind crossover trial, seven HF patients (6 men and 1 women, 54 ± 6 years of age, and body mass of 61 ± 11 kg, NYHA class II–III, ejection fraction 28.1 ± 2.5%,) were randomly assigned to either an in‐home cervicothoracic transcutaneous electrical nerve stimulation therapy (TENS: 30 min twice a day with 80 Hz frequency and pulse duration of 150 μs) or a sham control intervention (SHCI) for two weeks. Following a two‐month washout phase from TENS/SHCI, patients crossed over and started the opposite condition. Washout rate and heart‐to‐mediastinum ratio, indexes of cardiac sympathetic activity and innervation density, were obtained from planar 123l‐metaiodobenzylguanidine myocardial scintigraphy images at the beginning and end of each condition.ResultsBaseline washout rate (TENS 27.1 ± 4.4% vs. SHCI 25.2 ± 6.8%, p = 0.657), early (TENS 1.78 ± 0.1 vs. SHCI 1.78 ± 0.05, p = 0.916) and late (TENS 1.74 ± 0.19 vs. SHCI 1.68 ± 0.16, p = 0.222) heart‐to‐mediastinum ratios were similar between both conditions. While early and late heart‐to‐mediastinum ratio did not change throughout the study (p > 0.05), TENS, but not SHCI, promoted a significant reduction in the washout rate (TENS ‐ 12.8 ± 4.3 vs. STHI + 8.0 ± 8.9%, p = 0.03).ConclusionThese findings indicate that short‐term TENS therapy attenuates cardiac sympathetic overdrive in patients with heart failure with no impact on myocardial innervation density.Support or Funding InformationGrant Funding Source: CAPES, CNPq, FAPERJ, FINEP and IEN
Reduced Sensory Nerve Fiber Density in Ventricular Myocardium in a Rat Myocardial Infarction Heart Failure Model
Authors: Siano John , Li Ying , Dedkov Eduard I , Zhang Youhua 
Published: November 2023

IntroductionHeart failure (HF) results in autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, which in turn contributes to HF progression. The cardiac afferent sensory nerves play a critical role in mediating cardiovascular reflexes and in the neural regulation of cardiovascular function. However, the role of cardiac sensory nerves in mediating autonomic dysfunction in HF is less studied and it is unknown whether HF causes cardiac sensory nerve remodeling.MethodsMyocardial infarction (MI) was induced by left anterior coronary artery ligation in 9 rats, with 8 sham‐operated animals serving as controls. Two months after MI surgery, HF was confirmed in post‐MI rats (MI‐HF) by echocardiography and hemodynamic measurements. Sensory nerve fibers in ventricular myocardium were visualized on frozen histological sections by immunostaining with anti‐calcitonin gene related peptide (CGRP) antibody. The density of CGRP‐positive nerve fibers was determined on digitized images of non‐infarcted ventricular myocardium (remote from the infarction area) by using Image‐Pro Analyzer v.7.0 software.ResultsCompared to controls, the sensory nerve fiber density in non‐infarcted ventricular myocardium was significantly decreased in MI‐HF animals (see figure).ConclusionsThe development of HF in post‐MI rats is associated with a significant sensory nerve fiber remodeling with reduced sensory nerve fiber density.
Ginger Treatment Ameliorates Alcohol‐Induced Myocardial Damage by Suppression of Hyperlipidemia and Cardiac Biomarkers in Rats
Authors: Kesireddy Sathyavelu Reddy , Ganjikunta Venkatasubbaiah , Bhasha Shanmugam , Sahukaru Ravi 
Published: November 2023

BackgroundAlcohol‐induced hyperlipidemia is positively correlated with cardiovascular diseases. Several herbal extracts are reported to protect the cardiac injury and suppress the hyperlipidemia. However, the effect of ginger on alcohol‐induced hyperlipidaemia and myocardial damage remains unclear.ObjectiveThis study investigated the cardio protective properties of ginger ethanolic extract (Gt) on alcohol‐induced myocardial damage, and further distinguished the association between hyperlipidemia and occurrence of myocardial damage in rats.Materials and MethodsTwenty four Wistar male albino rats weighing 250 ± 20 g were divided into four groups includes, Normal control (NC) (0.9% NaCl), Ginger treated (Gt) (200 mg/Kg b.w.), Alcohol treated (At) (20%, 6 g/Kg b.w.) and Alcohol along with Ginger treatment(At+Gt). In this study, lipid profiles such as fatty acids, triglycerides, total cholesterol, phospholipids, low density lipoprotein and high density lipoproteins and Cardiac biomarkers includes LDH, AST, CK‐MB, cTn‐T and cTn‐I were examined in rats. In addition, histopathological studies were also conducted.ResultsWe found alcohol‐induced myocardial damage was associated with increased lipid profile except high density lipoprotein in alcohol treated (6 g/kg b.w.) rats compared to control rats while ginger treatment (200 mg/kg b.w.) reduced the lipid profiles except high density lipoproteins. Furthermore, elevated cardiac biomarkers activities with alcohol intoxication were significantly suppressed by ginger treatment. In addition, ginger treatment significantly minimized the myocardial damage induced by alcohol.ConclusionOur results conclude that ginger could protect from alcohol ‐ induced myocardial damage by suppression of hyperlipidemia and cardiac biomarkers.Support or Funding InformationUGC‐MRP‐F.No43‐586/2014(SR) dated 30‐10‐2015
Muscle Metaboreflex Activation in Young Healthy Men with a Family History of Hypertension
Authors: Kaur Jasdeep , Vranish Jennifer R. , Patik Jordan C. , Young Benjamin E. , Keller David M. , Fadel Paul J. 
Published: November 2023

Activation of metabolically sensitive skeletal muscle afferents (i.e., the muscle metaboreflex) contributes importantly to the muscle sympathetic nerve activity (MSNA) and pressor responses evoked by static handgrip exercise. Individuals with a positive family history of hypertension (+FHH) have been shown to evoke greater pressor responses to static handgrip exercise however, whether this is due to an exaggerated muscle metaboreflex remains unclear. A recent study demonstrated that young, healthy women with +FHH have an exaggerated muscle metaboreflex activation compared to women with no family history (‐FHH). However, whether men with +FHH also exhibit an augmented muscle metaboreflex response has not been investigated. Therefore, we tested the hypothesis that muscle metaboreflex activation is exaggerated in young men with +FHH. Young, healthy men (+FHH, n=7 and ‐FHH, n=13) performed 2 min of static handgrip exercise at 40% of maximal voluntary contraction followed by a 2 min period of post‐exercise ischemia (PEI) to isolate skeletal muscle metaboreflex activation. In addition, a cold pressor test (CPT) was performed as a generalized, sympathoexcitatory stimulus. Beat‐to‐beat arterial blood pressure (finger photoplethysmography), heart rate (ECG) and MSNA (peroneal nerve microneurography) were measured. Resting mean arterial pressure (MAP; +FHH: 99±3 vs. ‐FHH: 95±2 mmHg, p=0.34) and MSNA (+FHH: 12±1 vs. ‐FHH: 15±3 bursts/min, p=0.56) were similar between groups. The increase in MAP during PEI following 40% handgrip was not different between groups (+FHH: Δ22±3 vs. ‐FHH: Δ23±1 mmHg, p=0.52). However, the MSNA response during PEI was greater in +FHH (Δ20±1 bursts/min) compared to ‐FHH (Δ10±2 bursts/min, p=0.01). No difference was observed in MAP (+FHH: Δ20±5 vs. ‐FHH: Δ19±3 mmHg, p=0.82) or MSNA (+FHH: Δ14±4 vs. ‐FHH: Δ16±5 bursts/min, p=0.75) response to CPT between groups. These preliminary data suggest that a heightened muscle metaboreflex mediated sympatho‐excitation is present in young healthy men with a family history of hypertension.Support or Funding InformationNIH R15‐HL‐130906
Effect of Exercise Training on Neurovascular Control During Mental Stress in Patients with Acute Coronary Syndrome
Authors: Ferreira‐Santos Larissa , Martinez Daniel Godoy , Nicolau José Carlos , Moreira Humberto Graner , Alves Maria Janieire NN , Trombetta Ivani Credidio , Negrão Carlos Eduardo , Rondon Maria Urbana PB 
Published: November 2023

Patients with myocardial infarction present abnormal neurovascular control at rest and during physiological conditions. On the other hand, exercise training (ET) restores the autonomic control in these patients. However, the effect of ET on neurovascular control during a defense reaction of mental stress in patients with acute coronary syndrome (ACS) remains unknown. We tested the hypothesis that long‐term ET would decrease muscle sympathetic nerve activity (MSNA) and would increase the skeletal muscle vasodilatation during mental stress in ACS patients. Thirty‐four patients with ACS with preserved ventricular function were allocated in two groups: 1) ET (ACS‐ET, n=17) and 2) Untrained (ACS‐U, n=17). MSNA was recorded directly from the peroneal nerve by microneurography and forearm blood flow was measured by venous occlusion plethysmography. The six‐month ET program was supervised and consisted of three 60‐min exercise sessions/week. Mental stress was elicited by a mental challenge of Stroop Color Word Test during 3 minutes. MSNA significantly decreased during mental stress in the ACS‐ET group (P=0.002), but not in the ACS‐U group. In addition, in the post‐intervention period, the levels of MSNA during mental stress were significantly lower in the ACS‐ET group in compared with ACS‐U group (P=0.04). ET did not significantly change the forearm vascular conductance during mental stress. However, in the post‐intervention period, the forearm vascular conductance response was significantly higher in the ACS‐ET group compared with ACS‐U group (P<0.001). In conclusion, ET improves neurovascular control during a defense reaction of mental stress in patients with ACS. Therefore, these results emphasize the importance of prescribing ET in the treatment of these patients.Support or Funding InformationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2010/50048‐1); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq#475911/2013‐0, #309821/2014‐2 and #308068/2011‐4) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior‐ CAPES