title: Advanced echocardiography in adult zebrafish reveals delayed recovery of heart function after myocardial cryoinjury.
abstract: Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage.
authors: Department of Medicine III, Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany and DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors: Selina J
authors: SJ
authors: Hein
authors: Department of Medicine III, Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany and DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors: Lorenz H
authors: LH
authors: Lehmann
authors: Department of Medicine III, Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany and DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors: Mandy
authors: M
authors: Kossack
authors: Department of Medicine III, Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany and DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors: Lonny
authors: L
authors: Juergensen
authors: FUJIFILM VisualSonics Inc., Amsterdam, The Netherlands.
authors: Dieter
authors: D
authors: Fuchs
authors: Department of Medicine III, Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany and DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors: Hugo A
authors: HA
authors: Katus
authors: Department of Medicine III, Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany and DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors: David
authors: D
authors: Hassel
mesh_terms: D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000254:growth & development* / Q000503:physiopathology; D006352:Heart Ventricles / Q000254:growth & development / Q000503:physiopathology; D006801:Humans; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology*; D012038:Regeneration; D015027:Zebrafish / Q000254:growth & development / Q000502:physiology