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

• Published in: The Journal of surgical research Vol. 182; no. 2; pp. 331 - 338
• Main Authors: Fensterer, Tathyana F., MD, PhD, Keeling, W. Brent, MD, Patibandla, Phani K., PhD, Pushpakumar, Sathnur, MD, PhD, Perez-Abadia, Gustavo, MD, Bauer, Philip, PhD, Soni, Chirag V., PhD, Anderson, Gary L., PhD, Maldonado, Claudio, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2013
• Subjects: Animals; Complement; Endothelial Cells - physiology; Endothelium; Heart; Heart Transplantation; Ischemia-reperfusion injury; Liposomes; Liposomes - administration & dosage; Male; Myocardial Reperfusion Injury - prevention & control; Organ Preservation Solutions - pharmacology; Rat; Rats; Rats, Inbred F344; Surgery; Transplantation; Ventricular Dysfunction, Left - prevention & control; Heart; Ischemia-reperfusion injury; Rat; Complement; Transplantation; Liposomes; Endothelium
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2012.10.022

Abstract Background Myocardial injury after heart transplantation is a consequence of pathophysiologic events initiated by local ischemia/reperfusion injury that is further aggravated by the inflammatory response due to blood exposure to the pump’s artificial surfaces during cardiopulmonary bypass. The purpose of the present 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. 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 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 (15 min) and 4°C (45 min) and, after transplantation, were followed up for 2 h. Left ventricular function and the blood cardiac troponin I levels were quantified. Results Human umbilical vein endothelial cells treated with ST+FLVs had reduced C3b deposition and expression of adhesion molecules compared with ST alone ( P < 0.05). Donor hearts receiving ST+FLVs therapy had reduced left ventricular dysfunction and cardiac troponin I compared with ST alone. Conclusions We concluded that FLVs enhanced the cardioprotective effect of ST and reduced postischemic left ventricular dysfunction and myocardial damage. The mechanism of protection appears to be associated with the stabilization of endothelial cell membranes owing to incorporation of FLV-derived lipids.