Abstract

Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.

Highlights

  • A mammalian heart strictly controls the rhythm of the beat to meet the demand of the body for circulation

  • We found that the operation is able to boost the ECG signal, as indicated by about 10-fold higher amplitudes of P, QRS, and T waves, accompanied by significantly reduced background noise (Fig 1B)

  • 4.1 Reliable ECG signals can be obtained from adult zebrafish

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Summary

Introduction

A mammalian heart strictly controls the rhythm of the beat to meet the demand of the body for circulation. Heart rhythm is primarily initiated by the automatic beating of pacemaker cells located in the sinoatrial node (SAN), a specialized area in the upper right chamber of a mammalian heart. The initial innate electrical potential transmits from the SAN to the atrioventricular node (AVN) and passes to the His-Purkinje system. This well-controlled rhythmic contraction is modulated both positively by sympathetic nerves and negatively by parasympathetic. FP00093430 (https://www.mayoclinic.org/) to XX, the Ted and Loretta Rogers Cardiovascular Career Development Award Honoring Hugh C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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