Simultaneous inhibition of thrombosis and inflammation is beneficial in treating acute myocardial infarction

Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathways to limit myocardial IRI. Perfluorocarbon nanoparticles (PFC NP) were covalently coupled with an irreversible thrombin inhibitor, PPACK (Phe[D]-Pro-Arg-Chloromethylketone), and delivered intravenously to animals in a single dose prior to ischemia reperfusion injury. Fluorescent microscopy of tissue sections an