1.Cardiovascular Research Laboratory, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. 2. Cardiac Rehabilitation Center of Integrated Traditional Chinese and Western Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032. 3. Industrial Development Center, Shanghai University of Traditional Chinese Medicine, Shanghai 200032
Objective To establish a simple and reproducible model and its evaluation system for bradycardiac arrhythmia in Zebrafish. Methods Wild-type and heart-labeled GFP transgenic zebrafish were employed in this study after 24 h of fertilization. Twenty-four hpf (hour post-fertilization) zebrafish embryos were treated with various concentrations of verapamil, propafenone, metoprolol, amiodarone, and mexiletine for 48 hours, then the cardiac function and cardiotoxicity, including survival rate, heart rate, stroke volume, cardiac output, ejection fraction, area difference between ventricular diastole and systole and the distance between sinus venosus and bulbus arteriosus (SV-BA), were observed in each group. Results To evaluate drug toxicity, the median lethal concentration ( IC50 ) was ranked as propafenone < mexiletine < amiodarone < metoprolol and verapamil. After treatment with verapamil, the heart rate, cardiac output, ejection fraction and difference between ventricular diastolic and systolic areas significantly decreased in Zebrafish, while the distance of SV-BA increased. Treatment of propafenone reduced the heart rate and cardiac output in Zebrafish. Treatment of metoprolol decreased the heart rate in Zebrafish. Treatment of amiodarone decreased the heart rate and increased the distance of SV-BA in Zebrafish. Treatment of metoprolol increased the distance of SV-BA in Zebrafish. Conclusions Verapamil, propafenone, metoprolol and amiodarone all could be used to construct zebrafish models of bradycardiac arrhythmia, among which verapamil had the best efficacy. This study proposes the use of anti-arrhythmic drugs, particularly verapamil, to establish the bradycardiac arrhythmia model using zebrafish as well as the corresponding evaluation indicators. This study is of great significance to the research of bradycardiac arrhythmia and its drug development.