Capturing human-like digitalis effect and cardiotoxicity in adult zebrafish using in vivo dual-Einthoven-lead ECG and ex vivo epicardial optical mapping

Abstract

In humans, twelve-lead electrocardiogram (ECG) is an indispensable, accurate, rapid, and economical method for clinical evaluation of “digitalis effect” (earliest, nontoxic ECG manifestations of adequate cardiac tissue absorption) and digitalis cardiotoxicity (suppressant effects, excitatory effects, and hyperkalemia). In adult zebrafish, for which the canonical ECG recording method employs single lead, digitalis effect and cardiotoxicity are largely unknown. Here we demonstrate the first application of in vivo dual-Einthoven-lead ECG and Einthoven's-triangle construction as a novel reproducible method to reveal that normal adult zebrafish acutely recapitulate most of human digitalis effect and cardiotoxicity (except QT shortening).