Cardioprotective efficacy of ultrasound-targeted nitrofatty acid microbubbles in rat myocardial ischemia-reperfusion injury model

Abstract

Over 1 million Americans suffer from acute myocardial infarction (AMI) annually. Although mortality from AMI has decreased, post-AMI congestive heart failure is increasing due to microvascular obstruction (MVO). MVO comprises mechanical obstruction, along with oxidate stress and inflammation. Currently available treatments for MVO are not consistently effective. Hence, we have been developing ultrasound (US)-targeted microbubble cavitation (UTMC) as a potential treatment for MVO. Nitro-fatty acids (NFA) are pleiotropic signaling molecules with broad anti-inflammatory actions, potentially beneficial for the treatment of MVO. NFA are amphipathic thus can seamlessly integrate into the phospholipid shell of MBs. Thus, we have constructed microbubbles with NFA (NFABs) to treat ischemia-reperfusion injury (IRI) with UTMC in the rat myocardial model. Left anterior descending (LAD) coronary artery was ligated for 30 min, allowing for IRI. After 15 min of reperfusion, UTMC + NFABs therapy was administered. Echocardiography measurements were recorded at baseline, during ligation and post-treatment. Left ventricular fractional shortening (%) was calculated and NFA concentration in cardiac tissue was determined. UTMC with NFABs exhibited promising efficacy in improving fractional shortening post IRI, and in targeted myocardial delivery of NFA. Studies assessing ejection fraction, myocardial area at risk, histopathology, inflammatory burden, oxidative stress and cytoprotective biomarkers are underway.