Infusion of cardioplegia with monounsaturated lipids attenuates myocardial injury: involvement of lipid rafts in the protective effect (667.8)

Abstract

Myocardial ischemia/reperfusion injury (IRI) can lead to deleterious clinical outcomes following cardiopulmonary bypass (CPB). We developed fusogenic lipid vesicles (FLVs) formulated with monounsaturated lipids (MULs) that modulate endothelial cell (EC) adhesion molecule expression. The purpose of this study was two fold: 1) determine in a swine CPB model the effect of infusing crystalloid cardioplegia (CC)+FLVs in attenuating IRI; and 2) elucidate potential mechanisms by which FLV administration provides protection. We hypothesize that FLVs rapidly incorporate MULs into EC lipid raft microdomains (LRMs) altering their composition, which in turn interferes with EC activation signaling. To evaluate efficacy of FLV treatment swine hearts were infused with CC or with CC+FLVs and underwent 2h of cross‐clamp ischemia. After clamps were removed, cardiac function was evaluated during 2h of reperfusion. To evaluate potential cellular mechanisms of FLV protection, in vitro studies to visualize incorporation of MULs into EC LRMs using advanced fluorescent microscopy techniques were performed by transfecting cells with plasmid expressing green fluorescent protein‐labeled flotillin‐1, and by treating cells with rhodamine‐labeled FLVs. Results from CPB studies indicated that CC+FLVs treatment reduced myocardial injury and improved cardiac stroke work index, and results from in vitro EC studies indicated that incorporation of FLV MULs into membranes was predominantly associated with LRMs. We conclude that FLV induced incorporation of MULs attenuates myocardial injury after CPB, and that the protective effect appears to be associated with the incorporation of MULs into EC LRMs.Grant Funding Source: Supported in part by grants from NIH 1R42HL079855 and EndoProtech, Inc.