Advanced echocardiography in adult zebrafish reveals delayed recovery of heart function after myocardial cryoinjury

PLoS One. 2015 Apr 8;10(4):e0122665. doi: 10.1371/journal.pone.0122665. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Physiological Phenomena*
  • Disease Models, Animal
  • Echocardiography
  • Heart / growth & development*
  • Heart / physiopathology
  • Heart Ventricles / growth & development
  • Heart Ventricles / physiopathology
  • Humans
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / physiopathology*
  • Regeneration*
  • Zebrafish / growth & development
  • Zebrafish / physiology

Grant support

SH was supported by the Rahel-Goitein-Straus research fellowship of Heidelberg Medical School. LHL was supported by a fellowship of the Molecular Medicine Partnership Unit (MMPU) of the University of Heidelberg. DH, MK, LHL and HAK was supported by the German Center for Cardiovascular Diseases (DZHK, Partnersite Heidelberg/Mannheim) and by the BMBF (German Ministry of Education and Research). DH was supported by the Deutsche Forschungsgemeinschaft (DFG; HA 52819/4-1), the Ministry for Science, Research and Arts of Baden-Wuerttemberg (MWK), the Deutsche Stiftung für Herzforschung (DSHF) and the Federal Ministry of Education and Research (BMBF; 01ZX1409A). This work was supported by generous donations from the Klaus-Tschira and Dietmar-Hopp Stiftung. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.