The goal of this proposal is to validate the feasibility of the swine model to test our novel therapy for the prevention of postoperative atrial fibrillation (POAF). POAF is the most common complication from cardiac surgery affecting 30%-50% of patients after coronary artery bypass grafting and/or valve surgeries. POAF leads to increased heart failure and hospital stays, costing an excess of US$2 billion per annum. POAF is an independent predictor of the development of AF long term. POAF is a highly prevalent issue in the veteran population. We recently reported a 40% incidence of POAF at our institution, with a 30% 5-year risk of recurrence of AF compared to 3% without POAF. Overactivity of the cardiac autonomic nervous system (CANS), is an important substrate for both POAF and AF. We hypothesize that neuromodulation of CANS can suppress POAF. We recently published in a canine model of POAF, that microinjection of nanoformulated CaCl2 into cardiac ganglionated plexi (GP), a critical component of the CANS, during open heart surgery, suppresses/prevents POAF. The mechanism of action is by inducing neuronal apoptosis in GP thus protecting the heart from sympathetic surge and inducing reverse remodeling of the heart, with potentially long term suppression of AF.7 The goals of this proposal are to (a) validate our successful canine model of POAF in Yucatan miniature swine species (b) test the safety and efficacy of nCaCl2 for neuromodulation and suppression POAF vulnerability in swine. Validating the swine model facilitates clinical translation of our novel therapy with the significance of targeted, effective and safe therapy for POAF and potentially long term suppression of AF vulnerability in a high-risk population.
Post-operative atrial fibrillation (POAF) affects 30%-50% of patients after coronary artery bypass grafting and/or valve surgeries. POAF leads to increased heart failure, hospital stays, healthcare expenditures and predicts the development of late AF. Increased activity of the cardiac ganglionated plexi (GP), a key component of the cardiac autonomic nervous system (CANS), is an important trigger and substrate for POAF and AF. We recently published in a canine model, that microinjection of nanoformulated CaCl2 into GP induces neuronal apoptosis, dampens the overactivity of the CANS that occurs after cardiac surgery and suppresses/prevents POAF without adverse effects or myocardial damage. Our goal is to validate the feasibility of our canine POAF model in swine species, to test the safety, efficacy and neuromodulation mechanism of POAF suppression by nanoformulated CaCl2.The potential benefits is a safe, effective and cost- effective method to prevent POAF and reduce susceptibility to AF long term.
