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      Comparison of speckle-tracking echocardiography with invasive hemodynamics for the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic rat models

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          Abstract

          Background

          Measurement of systolic and diastolic function in animal models is challenging by conventional non-invasive methods. Therefore, we aimed at comparing speckle-tracking echocardiography (STE)-derived parameters to the indices of left ventricular (LV) pressure–volume (PV) analysis to detect cardiac dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus.

          Methods

          Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM (32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals (n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV analysis were performed. LV short-axis recordings were used for STE analysis. Global circumferential strain, peak strain rate values in systole (SrS), isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV contractility, active relaxation and stiffness were measured by PV analysis.

          Results

          In T1DM, contractility and active relaxation were deteriorated to a greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM. Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with active relaxation, while in T2DM SrE was related to cardiac stiffness, cardiomyocyte diameter and fibrosis.

          Conclusions

          Strain and strain rate parameters can be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM. STE corresponds to PV analysis and also correlates with markers of histological myocardial remodeling.

          Electronic supplementary material

          The online version of this article (10.1186/s12933-017-0645-0) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography.

          Echocardiographic imaging is ideally suited for the evaluation of cardiac mechanics because of its intrinsically dynamic nature. Because for decades, echocardiography has been the only imaging modality that allows dynamic imaging of the heart, it is only natural that new, increasingly automated techniques for sophisticated analysis of cardiac mechanics have been driven by researchers and manufacturers of ultrasound imaging equipment.Several such technique shave emerged over the past decades to address the issue of reader's experience and inter measurement variability in interpretation.Some were widely embraced by echocardiographers around the world and became part of the clinical routine,whereas others remained limited to research and exploration of new clinical applications.Two such techniques have dominated the research arena of echocardiography: (1) Doppler based tissue velocity measurements,frequently referred to as tissue Doppler or myocardial Doppler, and (2) speckle tracking on the basis of displacement measurements.Both types of measurements lend themselves to the derivation of multiple parameters of myocardial function. The goal of this document is to focus on the currently available techniques that allow quantitative assessment of myocardial function via image-based analysis of local myocardial dynamics, including Doppler tissue imaging and speckle-tracking echocardiography, as well as integrated backscatter analysis. This document describes the current and potential clinical applications of these techniques and their strengths and weaknesses,briefly surveys a selection of the relevant published literature while highlighting normal and abnormal findings in the context of different cardiovascular pathologies, and summarizes the unresolved issues, future research priorities, and recommended indications for clinical use.
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            Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways.

            Cardiovascular disease is the primary cause of morbidity and mortality among the diabetic population. Both experimental and clinical evidence suggest that diabetic subjects are predisposed to a distinct cardiomyopathy, independent of concomitant macro- and microvascular disorders. 'Diabetic cardiomyopathy' is characterized by early impairments in diastolic function, accompanied by the development of cardiomyocyte hypertrophy, myocardial fibrosis and cardiomyocyte apoptosis. The pathophysiology underlying diabetes-induced cardiac damage is complex and multifactorial, with elevated oxidative stress as a key contributor. We now review the current evidence of molecular disturbances present in the diabetic heart, and their role in the development of diabetes-induced impairments in myocardial function and structure. Our focus incorporates both the contribution of increased reactive oxygen species production and reduced antioxidant defenses to diabetic cardiomyopathy, together with modulation of protein signaling pathways and the emerging role of protein O-GlcNAcylation and miRNA dysregulation in the progression of diabetic heart disease. Lastly, we discuss both conventional and novel therapeutic approaches for the treatment of left ventricular dysfunction in diabetic patients, from inhibition of the renin-angiotensin-aldosterone-system, through recent evidence favoring supplementation of endogenous antioxidants for the treatment of diabetic cardiomyopathy. Novel therapeutic strategies, such as gene therapy targeting the phosphoinositide 3-kinase PI3K(p110α) signaling pathway, and miRNA dysregulation, are also reviewed. Targeting redox stress and protective protein signaling pathways may represent a future strategy for combating the ever-increasing incidence of heart failure in the diabetic population. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.

              Ventricular pressure-volume relationships have become well established as the most rigorous and comprehensive ways to assess intact heart function. Thanks to advances in miniature sensor technology, this approach has been successfully translated to small rodents, allowing for detailed characterization of cardiovascular function in genetically engineered mice, testing effects of pharmacotherapies and studying disease conditions. This method is unique for providing measures of left ventricular (LV) performance that are more specific to the heart and less affected by vascular loading conditions. Here we present descriptions and movies for procedures employing this method (anesthesia, intubation and surgical techniques, calibrations). We also provide examples of hemodynamics measurements obtained from normal mice/rats, and from animals with cardiac hypertrophy/heart failure, and describe values for various useful load-dependent and load-independent indexes of LV function obtained using different types of anesthesia. The completion of the protocol takes 1-4 h (depending on the experimental design/end points).
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                Author and article information

                Contributors
                csaba.matyas@gmail.com
                kovatti@gmail.com
                nemethbl@gmail.com
                o.attilio@gmail.com
                braunszm@gmail.com
                tokmarton@gmail.com
                barta.balint@gmail.com
                kalman.benke@gmail.com
                ruppertmis@gmail.com
                lakatosbalintka@gmail.com
                merkely.bela@gmail.com
                +36-1-458-6810 , radovitstamas@yahoo.com
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                16 January 2018
                16 January 2018
                2018
                : 17
                : 13
                Affiliations
                ISNI 0000 0001 0942 9821, GRID grid.11804.3c, Experimental Research Laboratory, Heart and Vascular Center, , Semmelweis University, ; Városmajor u. 68., 1122 Budapest, Hungary
                Author information
                http://orcid.org/0000-0001-6095-7611
                http://orcid.org/0000-0003-2320-6434
                Article
                645
                10.1186/s12933-017-0645-0
                5769218
                29338775
                88901200-d536-477b-a28d-ef529ac48f2a
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 October 2017
                : 23 December 2017
                Funding
                Funded by: Hungarian Scientific Research Fund
                Award ID: PD100245
                Award Recipient :
                Funded by: the National Research, Development and Innovation Office
                Award ID: NVKP_16-1-2016-0017
                Award Recipient :
                Funded by: Arrhythmia Research Foundation
                Funded by: Hungarian Academy of Sciences
                Award ID: János Bolyai Research Scholarship
                Award Recipient :
                Funded by: Human Resource Support Office
                Award ID: NTP-NFTÖ-16-0081
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100005881, Emberi Eroforrások Minisztériuma;
                Award ID: New National Excellence Program; ÚNKP-17-2-I-SE-15
                Award Recipient :
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2018

                Endocrinology & Diabetes
                speckle-tracking echocardiography,invasive hemodynamics,diabetic cardiomyopathy,cardiac dysfunction,heart failure,murine models,hfpef,hfref

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