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.
Subject(s)
Amiodarone/administration & dosage , Anti-Arrhythmia Agents/administration & dosage , Atrial Fibrillation/prevention & control , Drug Carriers , Heart Rate/drug effects , Pericardium/drug effects , Polyethylene Glycols/chemistry , Amiodarone/chemistry , Amiodarone/toxicity , Animals , Anti-Arrhythmia Agents/chemistry , Anti-Arrhythmia Agents/toxicity , Atrial Fibrillation/physiopathology , Disease Models, Animal , Drug Compounding , Drug Implants , Drug Liberation , Hydrogels , Male , Pericardium/physiopathology , Rats, Sprague-Dawley , Sus scrofa , Time FactorsABSTRACT
Biomaterials are a new treatment strategy for cardiovascular diseases but are difficult to deliver to the heart in a safe, precise, and translatable way. We developed a method to deliver hydrogels to the epicardium through the pericardial space. Our device creates a temporary compartment for hydrogel delivery and gelation using anatomic structures. The method minimizes risk to patients from embolization, thrombotic occlusion, and arrhythmia. In pigs there were no clinically relevant acute or subacute adverse effects from pericardial hydrogel delivery, making this a translatable strategy to deliver biomaterials to the heart.