Regeneration in a Giant Danio (D. aequipinnatus) Heart Cautery Injury Model

The paucity of mammalian cardiac myocyte (CM) proliferation following myocardial infarction (MI) and the remodeling of the necrotic tissue that ensues, results in non‐regenerative repair. While zebrafish (ZF) can regenerate from apical resection of the heart, there remains considerable interest in models where regeneration proceeds in the presence of necrotic tissue. We have developed and characterized a cautery injury model in the Giant danio (GD), a species closely related to ZF, where necrotic tissue remains part of the ventricle, yet regeneration occurs. By light and transmission electron microscopy (TEM), we have documented four temporally overlapping processes: 1) a robust inflammatory response analogous to that observed in MI, 2) concomitant proliferation of epicardial cells leading to wound closure, 3) resorption of necrotic tissue and its replacement by granulation tissue, 4) regeneration of the myocardial tissue driven by 5‐EDU and tritiated‐thymidine incorporating CMs. TEM reveals partially differentiated CMs in regenerating compact heart and adjacent trabeculae. We conclude that in addition to ZF, GD can serve as a useful model of heart inflammation, remodeling and regeneration.