The nitric oxide donor, diethylamine NONOate, enhances preservation of thedonor rat heart

Background: Ischemia/reperfusion injury to transplanted organs may be assoc iated with loss of endothelial release of nitric oxide. The aim of this stu dy was to determine whether supplementation of an extracellular-based cardi oplegic solution in routine clinical use at our institution with nitric oxi de las diethylamine NONOate) enhanced poststorage functionality of an isola ted working heart model. Methods: Excised hearts were ligated to an aortic cannula and immediately p erfused retrogradely with oxygenated Krebs solution at a hydrostatic pressu re of 100 cm H2O at 37 degrees C. This preparation was then converted to a working system by switching the supply of perfusate from the aorta to a lef t atrial cannula at a filling pressure of 15 cm H2O. After a 1-minute stabi lization period, baseline measurements of heart rate, aortic now, coronary artery flow, and cardiac output were performed. Oxygenated cardioplegic sol ution (0.1 mu mol/L), with or without NONOate, was then infused into the co ronary circulation. Hearts were then stored in the same solutions for 6 or 12 hours at 2 degrees to 3 degrees C. The hearts were then remounted on the perfusion apparatus and reperfused as before, and hemodynamic measurements were repeated. Water content of the hearts were then determined. Results: Addition of the nitric oxide donor significantly improved all hemo dynamic parameters measured after 12 hows storage and aortic flow at 6 hour s storage compared with the untreated control groups. There was no signific ant difference between the water contents of the NONOate-treated and contro l groups. Conclusions: The presence of the nitric oxide donor diethylamine NONOate wa s associated with significantly better preservation of coronary artery flow and cardiac function in the isolated rat heart after a 12-hour period of h ypothermic storage and suggests a novel use for this family of compounds in the transplantation context.