bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Wave Reflection in Patients with Duchenne Muscular Dystrophy (DMD)
Authors: Witman Melissa A , Katulka Elissa K , Hirt Alexandra E , Berube Felicia R , D'Agata Michelle N , McCulloch Michael A , Scavina Mena 
Published: June 2021

Cardiovascular complications are progressive in Duchenne Muscular Dystrophy (DMD) with cardiomyopathy/heart failure characterized as the leading cause of death in these young patients. Increased wave reflection augments pulsatile load on the heart and is known to be predictive of new onset heart failure in adults. Patients with DMD may have higher wave reflection as measured by augmentation index (AIx) but this has yet to be comprehensively studied in these patients. Given the incidence of dilated cardiomyopathy in DMD, a better understanding of the pulsatile load and ventricular‐arterial interactions could provide valuable insight into disease progression and management.PURPOSEThus, the purpose of this study was to characterize wave reflectance and pulsatile load with wave separation and wave intensity analyses in a group of patients with DMD compared to typically‐developing controls.METHODSAssessments were performed on 23 boys (10 DMD and 13 typically‐developing controls (CON)) between the ages of 8 and 18 years. A brachial artery oscillometric‐cuff device was used to record brachial artery pressure waveforms that were calibrated and synthesized to central pressure waves using a generalized transfer function. Pulse wave analysis (PWA) was performed to determine central blood pressures and AIx. Wave separation analysis was also used to determine the relative contributions of forward (Pf) and backward (Pb) pressure waves and reflection magnitude (RM=Pb/Pf).RESULTSPatients with DMD had a significantly higher augmentation index (AI) as measured by PWA (DMD: 21.2 ± 5 vs CON: 0.9 ± 2 %, p<0.05) but no difference in central pulse pressure (DMD: 34 ± 3 vs CON: 30 ± 1 mmHg). There was also no difference in Pf between groups (DMD: 27 ± 2 vs CON: 26 ± 2 mmHg). However, both Pb (DMD: 14.0 ± 1 vs CON: 11.7 ± 1 mmHg, p<0.05) and RM (DMD: 52.0 ± 1 vs CON: 43.5 ± 2 %, p<0.05) were significantly elevated in the children with DMD.CONCLUSIONThese preliminary data suggest that patients with DMD have higher wave reflection, which may indicate increased arterial stiffness and increased pulsatile load on the heart.Support or Funding InformationGrant support: NIH P20GM113125This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Nicotine on Cardiac Function and Structure
Authors: Oakes Joshua , Knowling Joselyn , Lazartigues Eric , Yue Xinping , Gardner Jason 
Published: June 2021

Nicotine is the addictive chemical in tobacco‐related products, such as cigarettes, water pipes, e‐cigs, and chewing tobacco. While the effects of smoke from cigarettes and cigars are well known, the rise in popularity of smokeless electronic cigarettes (e‐cigs) brings new questions about the effects of nicotine itself on the development of cardiovascular disease. These “smoke‐less” products have grown in popularity due to reduced costs, increased social acceptance, and a belief that e‐cigs are a less dangerous alternative to smoking.Nicotine use is associated with hypertension and may activate the renin‐angiotensin system when inhaled. The renin‐angiotensin system regulates blood pressure, and a major component of the system, angiotensin‐II (Ang‐II), can cause cardiac hypertrophy and fibrosis. However, most animal studies administer nicotine via infusion, and very little is known about the effects of chronically inhaled nicotine.Thus the goal of our study is to investigate the effects of chronic inhaled nicotine on cardiac function and structure.C57BL/6 male mice aged 8–12 weeks were used in this study. Mice were exposed to nicotine vapor in their home cage using an exposure system that provides control of chronicity and nicotine dosing. Mice were exposed for 12 hours/day corresponding with the dark cycle. Following 4 weeks of either nicotine or air exposure, subsets of these groups were implanted with osmotic mini‐pumps containing Ang‐II to induce hypertrophy and fibrosis. Cardiac function was assessed by ultrasound echocardiography and tissue samples collected for protein and mRNA analysis. While there was no significant change in left ventricular function, we found that nicotine blunted Ang‐II mediated hypertrophy in the posterior wall (0.83 ± 0.03 mm, n=19) compared to Ang‐II exposed mice (0.93 ± 0.02 mm, n=19, p< 0.01). While there were no differences in collagen 1 and 3 mRNA expression between groups, our preliminary data showed an increase in collagen I protein expression in nicotine exposed mice compared to air controls (1.27 ± 0.05 vs. 1 ± 0.09, n=2–3 respectively).In conclusion, while nicotine does not appear to affect left ventricular cardiac function, nicotine does blunt Ang‐II mediated hypertrophy. In addition, there is also evidence for increased cardiac collagen deposition in nicotine exposed mice. Future studies to measure right ventricular function, cardiomyocyte size, hypertrophic pathways, and cardiac fibroblast activity are in progress.Support or Funding InformationNHLBI R01 HL135635NIH Grant #R25GM121189This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Rats are Protected from the Stress of Chronic Pressure Overload Compared with Mice
Authors: Nishimura Koichi , Oydanich Marko , Zhang Jie , Vatner Dorothy E , Vatner Stephen F 
Published: June 2021

Little is known about differences in responses to cardiac stress in different rodent species, i.e., rats vs mice. The goal of this investigation was to compare the effects of chronic, 1‐month, thoracic aortic constriction (TAC) in Sprague Dawley rats and C57BL/6 mice. Sham and TAC procedures were conducted in both rodent groups. TAC, in the thoracic aorta, just distal to the aortic valve, induced similar left ventricular (LV) aortic pressure gradients across the aortic constriction, but there was no pressure gradient in sham operated animals. LV ejection fraction was no different in sham rats and mice (73 ± 1%), and did not fall with TAC in the rats, but fell significantly, p<0.05, in mice with TAC to 59 ± 2%. LV end diastolic pressure was also not different in sham rats and mice (5 ± 1 mmHg) and did not increase with TAC in rats, but increased, p<0.05, in TAC mice to 15 ± 2 mmHg. The next goal was to examine potential mechanisms mediating these major differences in LV function. First, we examined LV systolic wall stress, which was also similar in sham rats and mice (73 ± 1 kdyn/cm2) and did not rise significantly in TAC rats, but rose, p<0.05, to 117 ± 7kdyn/cm2 in TAC mice. Since TAC induces LV hypertrophy, which in turn, impairs subendocardial coronary perfusion and coronary reserve, and consequently LV function, angiogenesis and arteriogenesis were examined next, as these mechanisms could alleviate the coronary subendocardial hypoperfusion. Immunofluorescent Ki67 staining of capillaries and arterioles revealed increased angiogenesis, i.e., greater increases, p<0.05, in capillaries in TAC rats (6.7 ± 0.3 Ki67+Isolectin positive cells/field) than in TAC mice (4.2 ± 1.1 Ki67+Isolectin positive cells/field). Arteriogenesis was also increased more in TAC rats than TAC mice, reflected by greater increases, p<0.05, in Ki67 stained arterioles in TAC rats (19.8 ± 0.3 Ki67+SMCα positive cells/field) vs TAC mice (7.9 ± 1.2 Ki67+SMCα positive cells/field). Thus, rats are more resistant to development of cardiac failure with chronic TAC compared with mice. The mechanism of this protection involved reduced LV systolic wall stress and increased angiogenesis and arteriogenesis in the rats with chronic pressure overload.Support or Funding InformationFunding support: NIH R01 HL124282This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Administration of Losartan Improves Myocardial Functional Performance in Rats with High‐Fat Diet‐Induced Obesity
Authors: de Oliveira Silvio Assis , de Araújo Muzili Nayara , de Carvalho Marianna Rabelo , de Campos Dijon Henrique Salomé , Cezar Marcelo Diarcádia Mariano , Ota Gabriel Elias , de Morais Camila Souza , Okoshi Katashi , Okoshi Marina Politi , Cicogna Antonio Carlos , Martinez Paula Felippe 
Published: June 2021

Extensive evidence has shown that high‐fat diet is associated with chronic activation of the renin‐angiotensin system (RAS) and left ventricular remodeling. This study was developed to evaluate the impact of angiotensin‐1 (AT1) receptor antagonism on myocardial function in rats with high‐fat diet‐induced obesity.MethodsMale Wistar rats (n=48) were fed a control (2.9 kcal/g, C) or high‐fat (3.6 kcal/g, O) diet for 20 weeks. After the 16th week, the rats were assigned into four groups: C, O, CL, and OL. CL and OL groups received Losartan (30 mg/kg/day) in drinking water during four weeks. At the end of the experiment, body composition and systolic blood pressure were assessed, and echocardiogram analysis was performed. Mechanical performance of papillary muscles was evaluated under basal condition with 2.5 mM calcium ([Ca+2])o and after inotropic stimulation: post‐rest contraction (PRC) and change in extracellular [Ca+2]o from 1.0 to 2.5 mM.ResultsBoth O and OL groups presented higher body weight and adiposity than their respective controls (p<0.05). Systolic blood pressure did not differ among groups. O and OL groups had greater left ventricular weight‐to‐tibia length ratio and posterior wall shortening velocity (C 42.92±4.45; O 48.72±4.81; CL 42.82±3.60; OL 47.96±4.03 mm/s). In papillary muscles evaluation, CL presented reduced negative tension derivative (‐dT/dt) in comparison to the C group at basal condition. After 60 seconds of PRC, both O and CL had lower relative variations in ‐dT/dt (C 55.9±20.9; O 47.1±13.3; CL 47.7±15.9; OL 51.1±14.5%) and peak developed tension than C. Also, OL had higher relative variation in DT than CL and O (C 65.7±23.6; O 56.3±13.9; CL 58.0±17.4; OL 66.4±17.4%), while variation of positive tension derivative (+dT/dt) was increased in OL compared to CL and O groups. After increasing [Ca2+]o to 2.0 and 2.5 mM, the relative variation in DT and +dT/dt were higher in OL than CL and O, respectively. OL showed increased ‐dT/dt in comparison to CL at extracellular calcium concentrations of 1.5, 2.0, and 2.5 mM.ConclusionAngiotensin II antagonism with losartan improves myocardial functional performance in rats with high‐fat diet induced‐obesity.Support or Funding InformationFinancial support: CAPES; CNPq; FUNDECT/MS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mice with endothelium‐selective deletion of adenosine kinase are protected against pressure overload induced left ventricle contractile dysfunction
Authors: Davila Alec , Tian Yanna , Czikora Istvan , Li Jie , Su Huabo , Huo Yuqing , Bagi Zsolt 
Published: June 2021

Microvascular vasodilator dysfunction frequently accompanies myocardial contractile dysfunction, but the mechanistic interrelationship between these pathologies remains poorly understood, and hence therapeutic interventions are limited. We sought to determine if vascular endothelium selective inhibition of adenosine kinase (ADK), the major adenosine metabolizing enzyme, augments vasodilation and improves pressure‐overload induced left ventricle (LV) systolic and diastolic dysfunction. Mice with endothelium‐selective ADK deletion (ADKVECKO) and wild types (WT) underwent transverse aortic constriction (TAC) or sham surgery. We measured agonist‐induced vasodilation in isolated skeletal muscle arterioles and performed echocardiographic assessment of LV systolic and diastolic function. We found that TAC increased LV wall thickness and caused a progressive decline in ejection fraction (EF) as well as led to an increased deceleration time (DT), indicating the development of both LV systolic and diastolic dysfunction. TAC was also associated with impaired acetylcholine (ACh)‐induced vasodilation. ADKVECKO mice displayed a significantly augmented ACh‐induced vasodilation, which was not affected by inhibition of NO synthase, with N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME). ADKVEC‐KO mice that underwent TAC exhibited a lesser degree in decline in EF and maintained normal DT without changes in LV wall thickness when compared to WT mice. Collectively, these observations suggest that a selective genetic deletion of vascular endothelial ADK provides beneficial effects on both vasodilator and LV systolic and diastolic function in pressure overload‐induced cardiac pump dysfunction.Support or Funding InformationSupport: American Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In Praise of Failure and Fractals in Physiology
Authors: West Bruce J 
Published: June 2021

Pushing the natural variability from the central region of a probability distribution describing a process, out into the tails of the probability, has two effects: 1) the natural low‐level variability disappears from the policymakers field of vision, making everything appear calm and trouble free; 2) when a suppressed fluctuation does appear it is completely unexpected and devastating. Strategies that artificially suppress all variability to achieve short‐term stability of a complex environment, do just the opposite. Such deceptively calm environments eventually experience massive blowups, catching everyone off‐guard and undoing years of stability, often ending up in a far worse situation than their initial volatile state. An alternate strategy would be to take advantage of natural variability, by judiciously applying the innovator's mantra “fail small, fail often”. In this way local failures are induced in complex processes by natural variability, as is always the case. Failures are kept small through timely human intervention and catastrophic failure is thereby avoided.We examine the hypothesis that the control of physiological time series results from allowing the underlying process to fail in small ways, and on a fairly regular basis. The notion of suppressing the natural variability of such time series is shown to increase the likelihood of failure being catastrophic when it does occur. Herein we use the fractional probability calculus to frame our arguments and to parameterize the control process that tempers the Lévy process through a criticality‐induced potential.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Post‐MI Cardiac Remodeling and Malfunction in Mice Are Exacerbated by Cardiomyocyte‐restricted Ablation of the Uchl1 Gene
Authors: Wu Penglong , Li Yifan , Liu Jinbao , Wang Xuejun 
Published: June 2021

BackgroundUbiquitination is reversible and the reversed process, known as deubiquitination, is catalyzed by deubiquitinases (DUBs). UCHL1 is a DUB known to express highly and play an essential role in the nervous tissue; however, the (patho) physiological significance of UCHL1 in cardiomyocytes remains undefined. To fill this gap, we performed the present study, testing the hypothesis that UCHL1 in cardiomyocytes is dispensable for cardiac development but plays an important role in maintaining proteostasis in diseased hearts.Methods and ResultsCardiomyocyte‐restricted Uchl1 knockout (CKO) was achieved by coupling Uchl1flox/flox with transgenic Myh6‐Cre in mice. Littermate mice with a genotype of Uchl1flox/flox, Uchl1flox/+, or transgenic Myh6‐Cre were used as the control (Ctl). By 2 months of age, the CKO did not cause discernible abnormal phenotype, with myocardial total ubiquitinated proteins and proteasomal DUBs (USP14 and UCH37) remaining unchanged. Myocardial infarction (MI) was then surgically induced in 2–3 months old mixed‐sex Ctrl or CKO mice and characterized at 4‐weeks post‐MI. Compared with sham controls, significant increases in myocardial UCHL1 proteins but not USP14 and UCH37 were detected in Ctl MI but not in CKO MI, demonstrating that post‐MI myocardial UCHL1 upregulation occurs primarily in cardiomyocytes. Echocardiography revealed significantly greater left ventricular (LV) internal diameters and smaller ejection fraction (EF) and fractional shortening in CKO MI vs. Ctrl MI. LV pressure‐volume relationship analyses also revealed significantly reduced EF, cardiac output, stroke work, and minimum dP/dt in CKO MI vs. Ctrl MI. Western blot analyses showed that MI induced significant increases in total myocardial ubiquitin conjugates and the increases were more pronounced in CKO MI.ConclusionsUCHL1 in cardiomyocytes is dispensable for cardiac development but is upregulated in post‐MI hearts and protects against post‐MI cardiac remodeling and malfunction likely through supporting cardiac capability of maintaining proteostasis under a stress condition.Support or Funding InformationThis work is supported in part by NIH grants HL072166, HL085629, and HL13166.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluating Cardiorespiratory Responses to Slow Breathing in Young Healthy Individuals: FitBit “Relax Mode” versus RESPeRATE
Authors: Jette Evan D. , Adler Tessa E. , Niro Frank , Coovadia Yasmine , Jensen Dennis , Usselman Charlotte W. 
Published: June 2021

Device‐guided slow breathing has been tested in clinical populations (e.g., hypertension, type II diabetes) with the goal of reducing blood pressure (BP) via a sensitization of the baroreflex. The FitBit's “Relax Mode” and the RESPeRATE device are commercially available devices which acutely reduce an individual's respiration rate and, by extension, BP. To the best of our knowledge no studies have directly compared the cardiorespiratory effects of these devices. The purpose of this study was to compare acute respiratory and BP responses to the RESPeRATE device (RESP), the FitBit's Relax Mode (FB). We hypothesized that RESP would result in greater decreases in respiratory rate than FB, leading to larger decreases in BP. We evaluated the responses to a single bout of RESP (15 min) and FB (5 min) in young (mean±SD age: 23±1 y), healthy (BMI: 23±3 kg/m2; mean arterial BP [MAP]: 82±8 mmHg) individuals (n=2 men, n=3 women). To normalize the duration of the stimuli, we compared the mean of the responses to FB to the mean of the last 5 min of RESP; the order of devices was randomized between subjects. Both devices were effective in reducing respiration rate from baseline (RESP: 11.1±3.5 to 5.6±0.7 breaths/min; FB: 11.2±1.8 to 7.3±0.3; main effect of slow breathing: p<0.01; effect of device: p=0.4). In contrast, tidal volume expansion increased from baseline during slow breathing (RESP: 0.70±0.33 to 1.41±0.50 L; FB: 0.61±0.17 to 1.20±0.59; main effect of slow breathing: p<0.01; effect of device: p=0.6). However, there was no change in minute ventilation from baseline levels (RESP: 7.0±1.8 to 7.8±3.0 L/min; FB: 6.7±1.8 to 8.7±4.2; main effect of slow breathing: p=0.1; effect of device: p=0.9), suggesting that the subjects did not hyperventilate during either slow breathing condition. MAP decreased from baseline during slow breathing (RESP: 82±8 to 80±8 mmHg; FB: 82±8 to 81±7; main effect of slow breathing: p=0.01; effect of device: p=0.9). Conversely, a significant slow breathing by device interaction (p=0.05) revealed that diastolic BP (DBP) was reduced from baseline only in the RESP condition (69±7 to 67±8 mmHg, p<0.01); FB was not associated with a reduction in DBP (69±8 to 69±8 mmHg, p=0.2). Our preliminary data indicated that while RESP reduced respiratory rate similarly to the FB, RESP may be more effective than FB at acutely reducing DBP in young healthy adults.Support or Funding InformationThis project was supported by a Natural Sciences and Engineering Research Council Discovery Grant (CWU). TEA & YC were supported by the McGill Department of Kinesiology and Physical Education Graduate Excellence Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Epidural stimulation improves cerebral autoregulation and autonomic cardiac control in humans with spinal cord injury
Authors: Saleem Saqib , Darrow David A , Netoff Theoden I , Tzeng Yu‐Chieh , Samadani Uzma , Krassioukov Andrei , Phillips Aaron 
Published: June 2021

Spinal cord injury (SCI) results in impaired cerebrovascular buffering of blood pressure changes and cardiovagal baroreflex sensitivity. These impairments appear to be at least partially the result of disrupted spinal autonomic pathways after SCI, and likely contribute to high rates of unstable blood pressure control, orthostatic intolerance, vascular‐cognitive impairment and high risk of stroke in this population. Acute spinal cord epidural electrical stimulation has recently been shown to activate the sympathetic nervous system. We therefore reasoned that acute epidural spinal cord stimulation could improve cerebrovascular buffering of blood pressure as well as baroreflex functionality after SCI. We tested this hypothesis by assessing the beat‐by‐beat relationships between heart rate, mean arterial blood pressure, and middle cerebral artery blood velocity in several individuals with SCI at rest and with acute epidural electrical stimulation after surgical implantation. We found epidural stimulation acutely improved cerebrovascular buffering of blood pressure and cardiovagal baroreflex function in people with SCI, raising the possibility that this intervention may be a viable therapy for improving cerebrovascular health in this population.Sponsors:Minnesota State Office of Higher Education.Natural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchClinical Neurosciences Pilot Research Fund ProgramLibin Cardiovascular InstituteHotchkiss Brain InstituteCompute CanadaSupport or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Libin Cardiovascular Institute, Hotchkiss Brain Institute, Compute CanadaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.