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      Clinical use of submaximal treadmill exercise testing and assessments of cardiac biomarkers NT-proBNP and cTnI in dogs with presymptomatic mitral regurgitation

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          Abstract

          Exercise intolerance is the first symptom of heart disease. Yet an objective and standardised method in canine cardiology to assess exercise capacity in a clinical setting is lacking. In contrast, exercise testing is a powerful diagnostic tool in humans, providing valuable information on prognosis and impact of therapeutic intervention. To investigate whether an exercise test reveals differences between dogs with early stage mitral regurgitation (MR) and dogs without cardiac disease, 12 healthy beagles (healthy group, HG) and 12 dogs with presymptomatic MR (CHIEF B1 / B2, patient group, PG) underwent a six-stage submaximal exercise test (ET) on a motorised treadmill. They trotted in their individual comfort speed for three minutes per stage, first without incline, afterwards increasing it by 4% for every subsequent stage. Blood samples were taken at rest and during two 3-minute breaks in the course of the test. Further samples were taken after the completion of the exercise test and again after a 3-hour recovery period. Measured parameters included heart rate, lactate and the cardiac biomarkers N-terminal pro-B-Type natriuretic peptide and cardiac Troponin I. The test was performed again under the same conditions in the same dogs three weeks after the first trial to evaluate individual repeatability. Cardiac biomarkers increased significantly in both HG and PG in the course of the test. The increase was more pronounced in CHIEF B1 / B2 dogs than in the HG. N-terminal pro-B-Type natriuretic peptide increased from 435 ± 195 to 523 ± 239 pmol/L (HG) and from 690 to 815 pmol/L (PG). cTnI increased from 0.020 to 0.024 ng/mL (HG) and from 0.06 to 0.08 ng/ml (PG). The present study provides a method to assess exercise-induced changes in cardiac biomarkers under clinical conditions. The increase of NT-proBNP and cTnI is more pronounced in dogs with early-stage MR than in healthy dogs. Results indicate that measuring the parameters before and after exercise is adequate and taking blood samples between the different stages of the ET does not provide additional information. Also, stress echocardiography was inconclusive. It can be concluded that exercise testing, especially in combination with measuring cardiac biomarkers, could be a helpful diagnostic tool in canine cardiology.

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          The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.

          Heart failure is a syndrome characterized initially by left ventricular dysfunction that triggers countermeasures aimed to restore cardiac output. These responses are compensatory at first but eventually become part of the disease process itself leading to further worsening cardiac function. Among these responses is the activation of the sympathetic nervous system (SNS) that provides inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure, but eventually accelerates disease progression affecting survival. Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs including changes in: 1) peripheral baroreceptor and chemoreceptor reflexes; 2) chemical mediators that control sympathetic outflow; and 3) central integratory sites. The interface between the sympathetic fibers and the cardiovascular system is formed by the adrenergic receptors (ARs). Dysregulation of cardiac beta(1)-AR signaling and transduction are key features of heart failure progression. In contrast, cardiac beta(2)-ARs and alpha(1)-ARs may function in a compensatory fashion to maintain cardiac inotropy. Adrenergic receptor polymorphisms may have an impact on the adaptive mechanisms, susceptibilities, and pharmacological responses of SNS. The beta-AR blockers and the inhibitors of the renin-angiotensin-aldosterone axis form the mainstay of current medical management of chronic heart failure. Conversely, central sympatholytics have proved harmful, whereas sympathomimetic inotropes are still used in selected patients with hemodynamic instability. This review summarizes the changes in SNS in heart failure and examines how modulation of SNS activity may affect morbidity and mortality from this syndrome.
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            Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy.

            The relation of minor and major axes of the left ventricle was determined in 100 left ventriculograms performed in the right anterior oblique projection. This relation taken over a wide range of volumes was used to derive a theoretically correct equation for determination of ventricular volume by echocardiography. The final equation was: V =[7.0/2.4 +d] (D3), where V = volume and D = the echocardiographically measured internal dimension. In 12 patients without asynergy, this equation accurately and directly calculated end-systolic and end-diastolic volumes whether the left ventricle was small or large. However, in 12 patients exhibiting left ventricular asynergy the correlation between angiographically and echocardiographically determined volumes was poor. Thus, caution is recommended in the use of time-motion echocardiography to calculate ventricular volumes in patients with coronary artery disease and possible left ventricular asynergy.
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              Exercise-induced cardiac troponin elevation: evidence, mechanisms, and implications.

              Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations. Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 June 2018
                2018
                : 13
                : 6
                : e0199023
                Affiliations
                [001]Small Animal Clinic, University of Veterinary Medicine Hannover Foundation, Hannover, Germany
                Faculty of Animal Sciences and Food Engineering, University of São Paulo, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4577-3739
                Article
                PONE-D-17-38322
                10.1371/journal.pone.0199023
                6002043
                29902265
                95a9cf3b-76ed-4bd3-974b-186f1a958680
                © 2018 Wall et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 November 2017
                : 30 May 2018
                Page count
                Figures: 0, Tables: 5, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004350, Studienstiftung des Deutschen Volkes;
                Award Recipient :
                Funded by: Gesellschaft zur Förderung Kynologischer Forschung e.V.
                LW was the recipient of a scholarship from the "Studienstiftung des deutschen Volkes (German academic scholarship foundation)" https://www.studienstiftung.de/. The study was financially supported by the "Gesellschaft zur Förderung Kynologischer Forschung e.V." https://www.gkf-bonn.de/index.php/startseite.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Dogs
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Activity
                Physical Fitness
                Exercise
                Medicine and Health Sciences
                Sports and Exercise Medicine
                Exercise
                Biology and Life Sciences
                Sports Science
                Sports and Exercise Medicine
                Exercise
                Medicine and Health Sciences
                Sports and Exercise Medicine
                Biology and Life Sciences
                Sports Science
                Sports and Exercise Medicine
                Medicine and Health Sciences
                Cardiology
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Medicine and Health Sciences
                Cardiology
                Heart Failure
                Medicine and Health Sciences
                Complementary and Alternative Medicine
                Exercise Therapy
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                All data underlying the study are within the paper.

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