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
Zebrafish are being increasingly used as animal models for human diseases such as cardiomyopathy and neuroblastoma. Owing to a nearly fully sequenced genome and efficient genetics/chemical genetics, zebrafish open new research opportunities for human diseases research. The purpose of this study was to develop zebrafish ultrasound vibro-elastography (ZUVE) for measuring the shear wave speed of zebrafish. An adult female zebrafish was anesthetized for three minutes for the ZUVE testing. A 0.1 s gentle harmonic vibration was generated on the tail using a sphere tip indenter with 3 mm diameter. Shear wave propagation in the zebrafish was measured using a high frequency 18 MHz ultrasound probe. Shear wave speeds were measured at 300, 400, and 500 Hz. Shear wave speeds were, respectively, 3.13 ± 1.20 (m/s) for 300 Hz, 4.28 ± 1.36 (m/s) for 400 Hz, and 5.07 ± 1.45 (m/s) for 500 Hz for zebrafish 1 in a region of interest (ROI) which covered the central body. The shear wave speed dispersions were similar for four zebrafish and shear wave speeds ranged between 2.5 (m/s) and 5 (m/s) from 300 Hz to 500 Hz. The experimental setup and testing for a zebrafish lasted less than three minutes. All tested zebrafish were alive after testing. ZUVE is safe, fast, and noninvasive, making the testing of elastic properties of zebrafish feasible.
Subject(s)
Elasticity Imaging Techniques/methods , Tail/diagnostic imaging , Zebrafish , Animals , Feasibility Studies , Models, Animal , VibrationABSTRACT
Extravascular lung water (EVLW) is a basic symptom of congestive heart failure and other conditions. Computed tomography (CT) is standard to assess EVLW, but it requires ionizing radiation and radiology facilities. Lung ultrasound reverberation artifacts called B-lines have been used to assess EVLW. However, B-line artifact analysis relies on visual interpretation and subjects to inter-observer variability. We developed lung ultrasound surface wave elastography (LUSWE) to measure lung surface wave speed. This research aims to develop LUSWE to measure the change of lung surface wave speed due to lung water in an ex vivo swine lung model. The surface wave speeds of a fresh ex vivo swine lung were measured at four frequencies of 100 Hz, 200 Hz, 300 Hz, and 400 Hz. An amount of water was then filled into the lung through its trachea. Ultrasound imaging was used to guide the water filling until significant changes were visible on the imaging. The lung surface wave speeds were measured. An additional 120 ml of water was then filled into the lung. The lung surface wave speeds were then measured again. The results demonstrated that the lung surface wave speed decreased with respect to water content.
