Journal of the American Society of Echocardiography
Pre-Clinical InvestigationApplication of Speckle-Tracking Echocardiography in an Experimental Model of Isolated Subendocardial Damage
Section snippets
Methods
All animal procedures were performed in accordance with the guidelines of the German Law on the Protection of Animals. The experimental protocols (Figures 1C and 1D) were reviewed and approved by the authorities (Landesamt für Gesundheit und Soziales, Berlin, Germany). Animals used in this study served as placebo-treated control groups in ongoing projects and were kept under identical housing conditions (12-hour light/dark cycle, standard diet ad libitum). Data sets, histologic sections, and
Study Population
Animals were randomly assigned to both study protocol and treatment regime. Exclusively males were used in this study, aiming for better comparability and exclusion of hormonal fluctuation as a possible confounder.
Four animals (n = 3 in the first cohort, n = 1 in the second cohort) died in the course of ISO injections for reasons not further investigated (overall mortality under ISO treatment 12.5%; Supplemental Figure 1, available at www.onlinejase.com). Data from these animals were excluded
Discussion
In this experimental study we showed that pathologic changes within the subendocardium can be evaluated by assessment of LS using STE.
We demonstrated that in a small animal model of isolated subendocardial fibrosis, only LS and LSR allowed the assessment of functional impairment, while other strain values, as well as conventional parameters of LV systolic function, remained unaffected. Furthermore, global LS was found to be a superior predictor for the presence of subendocardial fibrotic
Conclusions
Our findings confirm the current concept that longitudinal mechanics of the left ventricle are determined mainly by subendocardial status. Consequently, longitudinal strain parameters are able to reflect subendocardial function and may contribute to assessment of early cardiac impairment, even in subclinical disease stages. Elevated TIMP-1 serum levels in combination with assessment of reduced longitudinal strain parameters might be a promising surrogate for subendocardial fibrosis.
Acknowledgments
We thank Dr. Franziska Schwarz (scivisto.com) for the scientific figure illustrations and Annelie Blumrich for proofreading. We are grateful to Dr. Dieter Fuchs and Dr. Magdalena Steiner (FUJIFILM VisualSonics) for providing insightful background information about the used software tools and excellent technical support. We further thank Beata Höft, Christiane Sprang, and Manuela Sommerfeld for their excellent technical assistance.
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This work was supported by Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK; BER 5.4 PR). Ms. Brix was supported by Deutsche Stiftung für Herzforschung. Ms. Betz was supported by Deutsche Gesellschaft für Kardiologie and DZHK. Dr. Foryst-Ludwig was supported by Deutsche Forschungsgemeinschaft (KFO 218/2), Deutsche Stiftung für Herzforschung, and DZHK (BER 5.4 PR). Dr. Grune was supported by DynAge, FU Berlin. Dr. Kintscher was supported by DFG (KFO 218/2), Else Kröner-Fresenius Stiftung (2014_A100), and DZHK (BER 5.4 PR).
Drs. Grune and Kintscher contributed equally to this work. Parts of this work will be used in the doctoral theses of Mr. Beyhoff and Ms. Betz.