Jose R Garcia1, Peter F Campbell2, Gautam Kumar3,4, Jonathan J Langberg3, Liliana Cesar5, Juline N Deppen6,3, Eric Y Shin3, Neal K Bhatia3, Lanfang Wang3, Kai Xu3, Frank Schneider3,7, Brian Robinson7, Andrés J García1, Rebecca D Levit8. 1. Woodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience (J.R.G., A.J.G.). 2. Georgia Institute of Technology, Atlanta. InnovatiëLifeSciences, Santa Clara, CA (P.F.C.). 3. Division of Cardiology, Department of Medicine (G.K., J.J.L., J.N.D., E.Y.S., N.K.B., L.W., K.X., R.D.L.). 4. Emory University School of Medicine, Atlanta, GA. Division of Cardiology, Atlanta VA Medical Center, Decatur, GA (G.K.). 5. South Atlanta Veterinary Emergency Specialists, Fayetteville, GA (L.C.). 6. and Walter H. Coulter Department of Biomedical Engineering (J.N.D.). 7. and Department of Pathology and Laboratory Medicine (F.S., B.R.). 8. Division of Cardiology, Department of Medicine (G.K., J.J.L., J.N.D., E.Y.S., N.K.B., L.W., K.X., R.D.L.) rlevit@emory.edu.
Abstract
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity. METHODS: Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter. RESULTS: Implantation of amiodarone-containing gel significantly reduced the duration of sustained AF at 21 and 28 days; inducibility of AF was reduced 14 and 21 days post-delivery. Off-target organ drug levels in the liver, lungs, thyroid, and fat were significantly reduced in animals treated with epicardial amiodarone gel compared with systemic controls in small-animal distribution studies. CONCLUSIONS: The pericardium is an underutilized therapeutic site and may be a new treatment strategy for AF and other cardiovascular diseases.
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity. METHODS: Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter. RESULTS: Implantation of amiodarone-containing gel significantly reduced the duration of sustained AF at 21 and 28 days; inducibility of AF was reduced 14 and 21 days post-delivery. Off-target organ drug levels in the liver, lungs, thyroid, and fat were significantly reduced in animals treated with epicardial amiodarone gel compared with systemic controls in small-animal distribution studies. CONCLUSIONS: The pericardium is an underutilized therapeutic site and may be a new treatment strategy for AF and other cardiovascular diseases.
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