Abstract
Cardiovascular diseases have been the leading cause of death worldwide for a long time. Ischemic heart disease such as myocardial infarction is a common type of cardiovascular diseases. During myocardial infarction, blood supply to the heart is decreased due to occlusion of coronary arteries. The subsequent shortage of nutrients and oxygen lead to cardiomyocytes death in the infarction region. If a patient survives from a myocardial infarction episode, the resulting scar tissues in the heart muscles may interfere the synchronized beating of the heart and will cause heart failure. On the other hand, cardiac arrhythmia is another life-threatening condition which may occur after heart attack or result from abnormal electrical activities in the heart. Similar to myocardial infarction, cardiac arrhythmia may lead to acute heart arrest and sudden death. There are increased efforts on research aiming to either prevent or treat this class of diseases. As an emerging model organism for human diseases, several features of zebrafish (Danio rerio), such as its rapid and external development, easily tractable genetics, conserved cardiovascular system, and transparency, make it ideal for cardiovascular research. Giving these unique advantages over other animal models, we used zebrafish to establish two major assessment platforms for biomedical research: one is cardiac repair model and the other is zebrafish electrocardiography model. In the first part of this thesis work, we found that applying the steroid anti-inflammatory drug during injury would hinder the cardiac repair capacity of zebrafish. The disrupted wound healing process accompanied with decreased angiogenesis and cell proliferation. In the second part of our work, we developed a new combinative formula of anesthetics for long-term anesthesia of zebrafish. This novel approach has minimized adverse effects in cardiac function, and its advantages are demonstrated by cardiac rhythm analysis using both the adult zebrafish and isolated heart electrocardiogram systems. In conclusion, we established a zebrafish-based assessment module for cardiovascular diseases that could enhance cardiac repair research in the future. The unique zebrafish electrocardiogram system may also enable cardiotoxicity profiling. Integration of the zebrafish cardiac repair model and ECG system serves not only as a comprehensive platform for cardiovascular research, but also as commercial CRO tools for pre-clinical drug screening.