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.
Subject(s)
Aging/genetics , Aging/physiology , Sick Sinus Syndrome/etiology , Sinus Arrest, Cardiac/etiology , Zebrafish/genetics , Zebrafish/physiology , Animals , Animals, Genetically Modified , Disease Models, Animal , Electrocardiography , Humans , Mice , Models, Cardiovascular , Mutation, Missense , NAV1.5 Voltage-Gated Sodium Channel/genetics , Sick Sinus Syndrome/genetics , Sick Sinus Syndrome/physiopathology , Sinus Arrest, Cardiac/genetics , Sinus Arrest, Cardiac/physiopathology , Species Specificity , Zebrafish Proteins/geneticsABSTRACT
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Subject(s)
Adult , Humans , Male , Sinus Arrest, Cardiac/genetics , /methods , Tachycardia, Ectopic Atrial/genetics , ElectrocardiographyABSTRACT
Familial hypokalemic periodic paralysis is an autosomal dominant muscle disorder characterized by episodic attacks of muscle weakness, accompanied by a decrease in blood potassium levels. It is based on genetic mutations in the genes CACNA1S (most frequent, encoding the skeletal muscle calcium channel) and SCN4A (10% of cases, encoding the sodium channel). Few cases have been reported with cardiac dysrhythmia. We report a rare case of a patient with a novel SCN4A mutation who presented, on ECG, extreme bradycardia and syncopal sinus arrest that required a temporary pacemaker implant
