bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of Continuous Postextrasystolic Pacing in the Human
Authors: Stein Paul M. 
Published: June 2021

Continuous postextrasystolic pacing is a potential positive inotropic treatment for several depressed myocardial states. The safety of this pacing, however, has been questioned since the mid‐1960's because the pacing markedly raises the myocardial oxygen consumption, thereby increasing the potential for proarrhythmia. To understand the actual safety of continuous postextrasystolic pacing, six clinical studies and case reports were reviewed involving a wide range of cardiovascular maladies (atrial or ventricular septal defect, congestive cardiomyopathy, heart failure, mitral or pulmonary stenosis, mitral, tricuspid, or aortic regurgitation, patent ductus arteriosis, mitral valve prolapse, coronary arterial‐arteriosclerotic heart disease, and pulmonary arterial hypertension):

Braunwald E., et al. Amer. J. Med. 37: 700–711, 1964.
Meijler, F. L. and D. Durrer. Bull. N. Y. Acad. Med. 41: 575–591, 1965.
Lister, J. W., et al. Am. Heart J. 73: 362–368, 1967.
Resnekov, L. Med. Clin. N. Amer. 54: 247–259, 1970.
Gerschwind, H., et al. J. Am. Coll. Cardiol. 4: 216–225, 1984.
Freudenberger, R., et al. J. Cardiac Fail. 14: 35–40, 2008.
Patients received paired or coupled atrial, ventricular, or dual‐chamber pacing. Continuous postextrasystolic pacing in 63 of 63 patients resulted in zero incidences of ventricular tachyarrhythmia induction, including in 7 with a compromised coronary circulation. Only when a seventh clinical study was reviewed, involving myocardial infarction‐associated cardiogenic shock, did any arrhythmia occur, and only in 1 of 5 cases:

Gourgon, R., et al. Paired Pulse Stimulation of the Heart. Proceedings of the Second Conference on Paired Pulse Stimulation and Postextrasystolic Potentiation in the Heart. 1968. pp. 36–51.
Hence, when coronary arterial blood flow and myocardial oxygen supply are not compromised, and in the vast majority of cases where it is, continuous postextrasystolic potentiation pacing is a safe positive inotropic technique.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Arginase exhibits negative regulation of respiration in isolated murine cardiac mitochondria independent of mitochondrial nitric oxide synthase
Authors: Mahalingam Padmini , Sakamuri Siva S. V. P. , Sperling Jared A. , Sure Venkata N. , Katakam Prasad V. G. 
Published: June 2021

ObjectiveMitochondrial dysfunction underlies the development of various cardiovascular diseases. Previously, we reported the presence of mitochondrial nitric oxide synthase (mtNOS) in cardiomyocytes and for the first time observed that NOS inhibitors decreased the state IIIu respiration in isolated cardiac mitochondria but had no significant effect on basal/state II or ATP production. These effects of NOS inhibitors on mitochondrial respiration in isolated mitochondria were significantly different than the effects on mitochondrial respiration in intact cells suggesting novel functional role of mtNOS. Arginase regulates the levels of arginine available for the local nitric oxide synthases, thereby regulating the NO production. Cardiomyocytes specifically express arginase II localized in mitochondria and has been shown to regulate cardiomyocyte contractility. We hypothesized that inhibition of arginase II increases respiration in isolated murine cardiac mitochondria in vitro.MethodsCardiac mitochondria were isolated from three‐month‐old C57bl6 (n= 4–5) mice and treated with specific arginase inhibitor, S‐(2‐boronoethyl)‐L‐cysteine hydrochloride, S‐(2‐boronoethyl)‐L‐cysteine, BEC (100μM) for 30 minutes in assay buffer containing 10 mM pyruvate and 2 mM malate. Mitochondria (5 μg/well) were plated into cell plates and oxygen consumption rate (OCR) was measured using Agilent Seahorse XFe24 analyzer after serial injections of ADP (5 mM), oligomycin (5 μM), FCCP (5 μM) and antimycin and rotenone (10 μM and 2 μM). Respiratory parameters were reported as OCR (pico moles of oxygen/minute).ResultsArginase inhibition did not significantly alter the basal/state II respiration (106.2 ± 6.2 vs 98.8 ± 1.6) or state IVo (87.1 ± 8.0 vs 80.9 ± 7.7) or proton leak (53.2 ± 11.6 vs 41.7 ± 5.7). Interestingly, arginase inhibition increased the ADP‐induced or state III respiration by 25% (329.9 ± 18.7 vs 263.5 ± 20.2, p=0.05) and ATP production by 30% (237.5 ± 13.5 vs 182.7 ± 15.5, p=0.03) compared to untreated mitochondria. Uncoupler‐induced or state IIIu respiration (state IIIu) showed strong trend towards increase by 33% (237.5 ± 13.6 vs 182.7 ± 15.5, p=0.059) in isolated mitochondria treated with arginase inhibitor.ConclusionsArginase II negatively regulates the mitochondrial respiration in the heart and thus along with mtNOS it may play critical role in cardiovascular physiology and pathophysiology.Support or Funding InformationSupport: National Institute of Health: National Institute of General Medical Sciences and National Institute of Neurological Disorders and Stroke (Katakam: R01NS094834).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Estrogen mitigates leptin's effect on blood pressure through the SOCS3 signaling cascade
Authors: Kaul Sakshi , Halaharvi Harikrishna , Barnes Maria J 
Published: June 2021

Estrogen has been purported to play a protective role against high blood pressure ‐ a possible explanation for the reduced prevalence of hypertension among pre‐menopausal women as compared to aged‐matched men. The loss of endogenous estrogen during menopause is correlated with a striking increase in the incidence of hypertension in women ‐ a leading risk factor of heart failure, stroke, and kidney disease. Thus, it is imperative to identify how estrogen attenuates hypertension. Our studies have demonstrated that leptin plays a significant role in augmenting blood pressure in the absence of estrogen. Bilateral ovariectomized (OVX) female rats were used to investigate the hypothesis that estrogen can mitigate leptin‐induced hypertension by increasing the expression of Suppressor of Cytokine Signaling 3 (SOCS3). SOCS3 is an inhibitor of the JAK/STAT signaling, a key pathway through which leptin increases blood pressure. OVX and control animals either received a sole intracerebroventricular injections of saline, leptin or estrogen, or a combination of saline/leptin or estrogen/leptin. Thirty minutes later, the hypothalami of animals that received a single injection were extracted and prepared for western blot analysis. Brains of the animals from the dual‐injection group were perfused and extracted for immunohistochemistry. Western blot analysis demonstrated that estrogen increases the expression of hypothalamic SOCS3 in the OVX group. Histological staining demonstrated that pretreatment with estrogen attenuated neuronal activation by leptin. Taken together, these data suggest that estrogen can attenuate leptin's effect on blood pressure by increasing the expression of SOCS3.Support or Funding InformationSupported by The Iowa Osteopathic Educational Research FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differences in Exercise‐Induced Blood Flow Patterns between Apparently Healthy Female and Male Subjects
Authors: Pena Marcelo , Pena Francisco J , Rodriguez Lisa , Morales‐Acuna Francisco J , Gurovich Alvaro N 
Published: June 2021

Studies suggest that aerobic exercise (AX) induced endothelial shear stress (ESS) may be a preventive measure for atherosclerosis. However, ESS can be different based on blood flow patterns and between males and females. Therefore, the aims of the present study were to identify changes in blood flow patterns in relation to aerobic exercise (AX) intensity and identify if blood flow patterns are different between females and males. To accomplish these aims 17 young healthy subjects (9 females and 9 males) between the ages of 18–35 were recruited to perform two AX tests on a stationary bicycle. The First test was a graded exercise test (GXT) and was used to determine the exercise intensities for the second test via blood lactate (BL) levels. The second test was performed 48–72 hours later and consisted of three stages of steady‐state AX intensities based in BL (low: <2 mmol/L; medium: 2–4 mmol/L; and high: >4 mmol/L). During both test, artery diameter and blood flow patterns (i.e.: ESS, direction, and presence of turbulence) in the subject's brachial artery was recorded using Doppler and high definition ultrasound. Afterwards, exercise induced endothelial shear stress and presence of turbulence were calculated using Womersley's approximation and Reynolds number (Re) calculation, respectively. Blood flow pattern was mainly antegrade in both males and females. ESS (dynes/cm2) and Re were intensity depended in both males and females. In addition, ESS and Re were similar between sexes at baseline, low, moderate, and high workloads. Interestingly, brachial artery diameter (mm) did not change with exercise intensity in both males and females; however, baseline diameter was smaller in females than males (Table).Blood Flow patterns between females and males are very similar. Intensity dependency for ESS and Re is seeing in both males and females. However, this study showed that there was a significant difference in arterial diameter only at baseline and that artery diameters do not change with exercise intensity. Interestingly, there was a trend for smaller artery diameters across all exercise intensities in females, which might help increasing ESS to compensate for lower systolic blood pressure.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Creatine Supplementation and High Intensity Interval Training on Glycemic Profile and Cardiac Morphology in Rats
Authors: Martinez Paula F , Morais Camila S , Ota Gabriel E , Carvalho Marianna R , Gomes Mariana J , Cruz Arthur DFC , Oliveira Jéssica ML , Oliveira Paola CS , Mendonça Maria LM , Okoshi Katashi , Okoshi Marina P , Oliveira‐Junior Silvio A 
Published: June 2021

BackgroundCreatine supplementation may induce insulin resistance, a condition associated with cardiac remodeling and also a risk factor for cardiovascular disease. High intensity interval training (HITT) improves glucose tolerance and promotes cardiac changes. This study evaluated the influence of creatine supplementation and HITT on glycemic profile and cardiac morphology in rats.MethodsMale Wistar rats (n=60) were allocated into four groups: sedentary control (C), control + creatine supplementation (Cr), control + physical exercise (Ex), and creatine supplementation + physical exercise (ECr). C and Ex groups were treated with standard commercial chow; Cr and ECr received the same chow supplemented with creatine 2%. Rats from Ex and ECr groups underwent into a treadmill‐HIIT protocol, 5 times per week, for 12 weeks. At the end of the experiment, glycemic profile was analyzed by glucose and insulin tolerance tests (GTT and ITT, respectively), and functional capacity was assessed by maximal exercise test on treadmill. Cardiomyocyte cross‐sectional area and myocardial collagen interstitial fraction were evaluated in left ventricle histological sections stained with hematoxylin‐eosin and Picrosirius red, respectively. Statistics: two‐way ANOVA and Tukey.ResultsFunctional capacity was improved in exercised groups compared to respective controls. Considering glycemic response in GTT, the area under curve (AUC) was lower in Ex and ECr than in C and Cr. In ITT, AUC was lower in Ex than C and ECr. Atria weight and atria weight‐to‐body weight ratio were higher in ECr than Ex and atria weight‐to‐body weight ratio was higher in Cr than C. Heart weight‐to‐body weight ratio was higher in ECr than Cr and Ex. Left and right ventricle weight was similar between the groups. Myocyte cross‐sectional area (C 227±26, Cr 216±22, Ex 284±27, ECr 297±7 μm2) and left ventricle collagen interstitial fraction (C 1.96±1.79, Cr 1.98±1.28, Ex 2.36±2.00, ECr 2.49±1.80 %) were higher in Ex and ECr than C and Cr.ConclusionHIIT improves glucose and insulin tolerance. Creatine supplementation impairs insulin tolerance in exercised rats. HIIT promotes cardiomyocyte hypertrophy and increases myocardial collagen interstitial fraction without significant influence of creatine supplementation.Support or Funding InformationCAPESThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intensity of Voluntary Physical Exercise Affects Vesicle Development and Body Composition in an Animal Model of Endometriosis
Authors: Velazquez Johnathan , Cruz Myrella L , Chompre Gladys , Rivera‐Mendez Raquel M , Maldonado Nicmarie , Appleyard Caroline B 
Published: June 2021

Endometriosis is a gynecological chronic condition caused by endometrial tissue migration outside of the uterine cavity. Some symptoms associated with this inflammatory disease are chronic pelvic pain, infertility and painful menstrual cycles. Physical activity has been shown to promote a healthy lifestyle with beneficial effects on chronic inflammatory conditions.HypothesisIntensity of voluntary physical exercise on running wheels has an impact on body composition and will reduce vesicle development in an endometriosis animal model.MethodsEndometriosis (Endo) was induced (day 0) by suturing uterine horn tissue on the intestinal mesentery of female Sprague‐Dawley rats. Our control rats (Sham) received sutures with no implants. Endo exercise rats were exposed to voluntary exercise in running wheels 14 days before surgery until day of sacrifice (day 60). Sham control and another Endo group were not exposed to exercise. Running wheel activity data (speed, distance and intensity) was collected using Scurry Activity System software. Weight change and food consumption were measured throughout the protocol. At sacrifice, vesicles were collected and measured if present. Mesenteric fat, gastrocnemius and soleus muscles were dissected, weighed and collected.ResultsThe Endo exercise group had significantly decreased vesicle size (20.25±5.84mm2) compared to the Endo no exercise group (50.27±9.48mm2, p<0.05). A tendency towards smaller vesicles was observed with increased exercise intensity. The Endo exercise group showed a trend towards gaining less weight, while having a significantly higher food consumption after surgery (p<0.001). The Endo no exercise group had significantly higher amounts of mesenteric fat when compared to the Sham control and Endo exercise groups (p<0.05). The muscle/fat ratio was also increased in the Endo exercise group when compared to the Endo no exercise group indicating differences were due to less presence of fat rather than differences in muscle weight following exercise.ConclusionPhysical exercise ameliorates the development of vesicles and promotes decreased body fat composition in an animal model of endometriosis. The intensity of voluntary exercise appears to contribute towards the degree of impact on this condition. These results reinforce the potential beneficial effects of voluntary physical exercise as part of a daily routine to reduce endometriosis symptoms in patients.Support or Funding InformationSupported in part by P20GM103475‐16 & R15AT009915This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physical Activity and Blood Pressure Reactivity in Young Women with a Family History of Hypertension
Authors: Welti Laura M , Matthews Evan L , Greaney Jody L , Wenner Megan M 
Published: June 2021

Healthy normotensive young adults with a positive family history of hypertension (+FH) have increased risk of developing hypertension. Our laboratory has recently demonstrated that young normotensive women +FH display exaggerated blood pressure (BP) reactivity to acute laboratory stressors. Regular aerobic physical activity has been shown to attenuate BP reactivity in populations at risk for future hypertension, however it is unknown whether regular physical activity modulates BP reactivity in +FH young women.PurposeTo test the hypothesis that young women with +FH reporting regular aerobic physical activity would demonstrate blunted BP reactivity compared to sedentary +FH women.MethodsWe retrospectively analyzed beat‐by‐beat mean arterial pressure (MAP; Finometer) in 14 young women with +FH during three sympathoexcitatory maneuvers: two minutes of a cold pressor test (CPT), two minutes of isometric handgrip exercise at 30% of maximal voluntary contraction (HG), and three minutes of post‐exercise ischemia (PEI). Physical activity data were self‐reported on a standard medical history questionnaire. Women who reported at least four days of aerobic physical activity per week (thus exceeding minimum guidelines) were considered regularly active (+PA; n=7), and less than three days per week were inactive (−PA; n=6). Dare are presented as mean ± SD.ResultsResting MAP (−PA: 75±10 vs. +PA: 83±18 mmHg: P=0.26) and resting heart rate (HR) (−PA: 75±10 vs. +PA: 60±7 bpm: P=0.06) were not different between groups. BP reactivity during the CPT (ΔMAP: −PA 11±3 vs. +PA 13±7 mmHg, P=0.97), HG (ΔMAP: −PA 18±6 vs.+PA 23±12 mmHg, P=0.71), and PEI (ΔMAP: −PA 14±5 vs. +PA 22±10 mmHg, P=0.16) were not different between groups. Additionally, HR responses during the CPT (ΔHR: −PA 6±8 vs.+PA 4±7 bpm, P=0.74), HG (ΔHR: −PA 14±9 vs. +PA 20±11 bpm, P=0.27) and PEI (ΔHR: −PA 8±8 vs. +PA 3±9 bpm, P=0.45) were not different between groups.ConclusionsThese preliminary data suggest that self‐reported regular aerobic physical activity may not modulate BP responses to sympathoexcitatory stimuli in young women with +FH.Support or Funding InformationSupported by NIH Grant P20 GM 113125, P20 GM 103446, U54 GM 104941, and The University of Delaware Research FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kvβ2 deletion results in hindlimb muscle fibre type switching and enhanced endurance capabilities
Authors: Tur Jared , Chapalamadugu Kalyan C , Tipparaju Srinivas M 
Published: June 2021

The Kvβ2 subunit, a member of the Kv (voltage‐gated potassium channel) auxiliary subunits is a dynamic protein interacting with many protein. Previous research has highlighted Kvβ2's abundance during myogenesis and its interactions with key contractility proteins including calmodulin and myosin filaments. Recently we demonstrated that Kvβ2 knockout (KO) mice have a significant increase (+100%) in type I muscle fiber (MHCI) expression within the Soleus muscle compared with wild‐type control mice. Similarly, a significant increase (+47%) in MHCI expression within the Gastrocnemius muscle was also observed within KO mice compared with wildtype. Based upon the deletion of Kvβ2 resulting in altered myofibre distribution towards a slower phenotype, we hypothesize that Kvβ2 KO mice have greater endurance capabilities via a greater presence of oxidative muscle fibers. Indeed, preliminary data utilizing 12–20 week old Kvβ2 KO male mice showed significantly (p<0.01) increased average time in the inverted hang test (534±52s vs. 159±44s) compared with control wildtype. Additional endurance testing utilizing the rotarod demonstrated Kvβ2 KO mice again performed for longer at a given rpm when compared with control mice. While endurance based activities were significantly increased in Kvβ2 KO mice little change was noted in activities which are predominantly fast‐twitch reliant. Grip strength analysis measuring overall force generated demonstrated no significant difference between Kvβ2 KO and control (111±2gF vs. 118±5gF) mice. Overall, this is the first report identifying that genetic deletion of Kvβ2 leads to an increased endurance capacity resulting from a substantial increase in type I muscle fiber expression in hindlimb muscles.Support or Funding InformationThis Research work was funded by National Institutes of Health (NIH) Grant R01‐HL‐102171 (S. M. Tipparaju).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hemodynamic Response to Activation of the Exercise Pressor Reflex during Dynamic Plantar Flexion in Peripheral Arterial Disease Patients
Authors: Kim Danielle Jin‐Kwang , Kuroki Marcos , Cui Jian , Pai Samuel , Blaha Cheryl , Luck J. Carter , Gao Zhaohui , Miller Amanda J. , Sinoway Lawrence 
Published: June 2021

Patients with peripheral arterial disease (PAD) have an accentuated exercise pressor reflex (EPR). The underlying hemodynamic changes responsible for the exaggerated EPR, and the effect of this on blood flow to the exercising limb is unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the ischemic exercising muscle.METHODSEleven PAD patients and 11 age, and sex‐matched subjects without PAD (control) performed dynamic plantar flexion (PF) using their symptomatic leg at progressive workloads of 2 to 12 kg (increased by 1 kg/min until the onset of fatigue). We measured heart rate (HR), beat‐by‐beat blood pressure (BP), femoral blood flow velocity (FBV), and near‐infrared spectroscopy derived tissue oxygen saturation (SmO2) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the BP tracings.RESULTSMean arterial blood pressure (MAP) was significantly augmented in PAD compared to controls during PF (P < 0.001). This was accompanied by an equal rise in CO in the two groups. Of note, TPR decreased in controls, whereas it increased in PAD. The increase in femoral blood flow velocity was greater during exercise in PAD as compared to controls (P = 0.0021), however, the increased FBF in the two groups was the same. Despite the fact the flow was not different between PAD and control group, SmO2 of the exercising limb remained significantly lower in PAD compared to control (P < 0.001).CONCLUSIONWe conclude that the exaggerated pressor response in PAD is mediated by an abnormal response in TPR, which augments redistribution of blood flow to the exercising muscle, leading to an equal rise in FBF compared to controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD.Support or Funding InformationSupported by National Institutes of Health Grants P01 HL134609 (Sinoway) and UL1 TR002014 (Sinoway).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.