Year: 2015
Type: dissertation
Abstract: Background: Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with significant morbidity and mortality. Hypothesis: “Atrial” cardiomyocytes generated from hESCs will recapitulate the key hallmarks of human AF in a 2 dimensional tissue model, as well as demonstrate the expected electrophysiologic changes in response to drugs. Methods and Results: Our “atrial” cardiomyocytes were 80-90% positive for cardiac troponin, were enriched for the atrial markers ANF and KCNJ3, and lacked ventricular markers (MYL2 and IRX4). The “atrial” cells mimicked the human electrophysiologic phenotype with the majority (90%) demonstrating atrial like action potentials. Optical mapping of multicellular cell sheets was performed on rotors at baseline, after induction of rotor formation and with the addition of commonly employed antiarrhythmic drugs. Conclusions: We have successfully generated a human model of AF in vitro and demonstrated its utility in screening for known, and unpredicted effects of commonly employed anti-arrhythmics.
Source: TSpace (University of Toronto)
Author: Zachary Laksman
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2778428079