Richardson, Eric Stephen2009-08-052009-08-052009-05https://hdl.handle.net/11299/52393University of Minnesota Ph.D. dissertation. May 2009. Major: Biomedical Engineering. Advisor: Paul A. Iaizzo, PhD. Professor of Surgery, Integrative Biology and Physiology, and Anesthesiology. 1 computer file (PDF); x, 240 pages. Ill. (some col.)Anti-arrhythmic agents are known for their narrow therapeutic window and common side effects. Delivery of anti-arrhythmic agents into the pericardium has shown to increase their efficacy and minimize their side effects. My work has focused on evaluating the clinical potential of intrapericardial (IP) anti-arrhythmic delivery. This has included working with physicians to identify appropriate clinical applications, developing devices to aid in pericardial drug delivery, and carrying out several large animal studies to test efficacy. In swine models of sinus tachycardia, atrial fibrillation, and ischemia-induced ventricular tachycardias, we have shown the pharmacodynamic benefits of IP-delivered metoprolol, amiodarone, and docosahexaenoic acid. Pharmacokinetic data show that minimal amounts of drug reach the systemic circulation. We propose that IP delivery of anti-arrhythmic agents has potential to maximize therapeutic benefits while minimizing side effects, particularly in the settings of post-operative atrial fibrillation and inappropriate sinus tachycardia.en-USAnti-arrhythmic AgentDrug DeliveryPericardiumBiomedical EngineeringThesis or Dissertation