Abstract

In the last two decades, the zebrafish has emerged as an important model species for heart regeneration studies. Various approaches to model loss of cardiac myocytes and myocardial infarction in the zebrafish have been devised, and have included resection, genetic ablation, and cryoinjury. However, to date, the response of the zebrafish ventricle to cautery injury has not been reported. Here, we describe a simple and reproducible method using cautery injury via a modified nichrome inoculating needle as a probe to model myocardial infarction in the zebrafish ventricle. Using light and electron microscopy, we show that cardiac cautery injury is attended by significant inflammatory cell infiltration, accumulation of collagen in the injured area, and the reconstitution of the ventricular myocardium. Additionally, we document the ablation of cardiac nerve fibers, and report that the re-innervation of the injured zebrafish ventricle is protracted, compared to other repair processes that accompany the regeneration of the cauterized ventricle. Taken together, our study demonstrates that cautery injury is a simple and effective means for generating necrotic tissue and eliciting a remodeling and regenerative response in the zebrafish heart. This approach may serve as an important tool in the methods toolbox for regeneration studies in the zebrafish.

Highlights

  • Cardiovascular diseases remain the number one cause of death in the economically developed world [1]

  • We demonstrate that cauterization is an effective and reliable method to create thermal necrotic injury in the adult zebrafish heart, enabling studies of cardiac remodeling and regeneration

  • We have previously described the ultrastructural characteristics of the junctional region between the compact and spongy trabeculated myocardium in the uninjured zebrafish heart, documenting the structural heterogeneity of cardiac myocytes in that region [49]

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Summary

Introduction

Cardiovascular diseases remain the number one cause of death in the economically developed world [1]. They comprise genetic and lifestyle-linked diseases such as atherosclerosis that can lead to stroke and myocardial infarction (MI). The available literature on mammals demonstrates that the adult heart has very limited or non-existent ability to regenerate damaged myocardial tissue [5,6]. This limitation is due in whole or in part to the terminally differentiated state of adult ventricular cardiac myocytes [7,8,9]. Clinical therapies that aim at recovering myocardial function following

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