Cautery Injury Response in the Zebrafish Heart

Abstract

Using cauterization of the ventricular myocardium, previous studies in our lab have shown evidence of matrix remodeling as well as robust cardiac regeneration in the giant danio, a species closely related to the zebrafish. Various approaches to ventricular injury, including resection, cryoinjury, and genetic ablation have been used in zebrafish, resulting in differential responses in cardiac remodeling, the initiation and the rate of progression of cardiac regeneration. To date, responses to cardiac cautery injury have not been studied in the zebrafish heart. Hence, we aimed to characterize the ventricular myocardium response to this particular approach to heart injury. Using light and electron microscopy, in conjunction with myeloperoxidase staining, Edu incorporation in cardiac myocytes, Masson's Trichome and picrosirius red/fast green staining, we studied the repair of cauterized zebrafish hearts from 3 to 90 days post‐surgery. We found that cauterization results in regional tissue necrosis that was followed by marked infiltration of inflammatory cells, subsequent accumulation and resorption of connective tissue, and a gradual regenerative response. In addition, we used wheat germ agglutinin staining to document the progressive reconstruction of the damaged compact/cortical myocardium. Our study shows that ventricular cauterization is a simple and reproducible alternative approach to create myocardial necrosis, and to elicit matrix remodeling and cardiac regenerative responses in the zebrafish heart.Support or Funding InformationP.J.L. is supported by NIH 1 R15 HD084262‐01, Donald E. Town Faculty Fellowship, and Faculty Development Funds at DePauw University