Enhanced preservation of the rat heart after prolonged hypothermic storage with the 21-aminosteroid compound U74500A

Abstract

Background. The formation of reactive oxygen species has been postulated to play a role in the initiation of tissue damage associated with ischaemia/reperfusion injury in donor hearts after hypothermic preservation. The aim of this study was to determine whether addition of U74500A to an aspartate-enriched, extracellular-based cardioplegic solution enhanced function of donor rat hearts after prolonged hypothermic storage. Methods: Excised hearts were ligated to an aortic cannula and immediately perfused retrogradely with oxygenated Krebs' solution. This preparation was then converted from Langendorff to working mode. After a 1-min stabilisation period, baseline measurements of heart rate, aortic flow, coronary flow and cardiac output were performed. Oxygenated cardioplegic solution, with or without U74500A (30 μM), was infused into the coronary circulation. Hearts were stored in the same solutions for 6 or 12 hours at 2–3°C. The hearts were reperfused and haemodynamic measurements were repeated. Water content of the hearts was determined. Results and Conclusions: Addition of lazaroid significantly improved all haemodynamic parameters measured after 12 hours storage and aortic flow at 6 hours storage compared with the untreated and vehicle control groups. The presence of the lazaroid, U74500A, was associated with significantly better preservation of coronary flow and cardiac function in the isolated rat heart after 6 or 12 hours of hypothermic storage. This suggests a novel use for this family of compounds in the transplantation context.