Stabilizing endothelium of donor hearts with fusogenic liposomes reduces myocardial injury and dysfunction

Abstract

Background Myocardial injury after heart transplantation is a consequence of pathophysiological events initiated by local ischemia/reperfusion (IR) injury that is further aggravated by the inflammatory response due to blood exposure to the pump’s artificial surfaces during cardiopulmonary bypass (CPB). The purpose of this study was to determine the effectiveness of fusogenic lipid vesicles (FLVs) in enhancing the cardioprotective effect of St. Thomas organ preservation solution (ST). We hypothesized that donor hearts preserved with ST-FLVs will stabilize the endothelium during reperfusion, which in turn will reduce both endothelial barrier dysfunction and myocardial damage. Materials and methods To examine the effect of ST-FLVs therapy in vitro, C3b deposition and adhesion molecule expression studies were performed on human umbilical vein endothelial cells (HUVECs) challenged with plastic-contact-activated plasma. To assess the therapy in vivo, a cervical heterotopic working heart transplantation model in rats was used. Donor hearts were preserved for 1 h at 27°C (15min) and 4°C (45min), and after transplant were followed for 2 h. Left ventricular (LV) function and blood cardiac troponin I (cTnI) levels were quantified. Results HUVECs treated with ST-FLVs had reduced C3b deposition and expression of adhesion molecules compared to ST alone (P<0.05). Donor hearts receiving ST-FLVs therapy had reduced LV dysfunction and cTnI compared to ST alone Conclusion We conclude that FLVs enhance the cardioprotective effect of ST and reduce post-ischemic LV dysfunction and myocardial damage. The mechanism of protection appears to be associated with the stabilization of endothelial cell membranes due to incorporation of FLV-derived lipids.