The nitric oxide donor, diethylamine NONOate, enhances preservation of the donor rat heart.
BACKGROUND
Ischemia/reperfusion injury to transplanted organs may be associated with loss of endothelial release of nitric oxide. The aim of this study was to determine whether supplementation of an extracellular-based cardioplegic solution in routine clinical use at our institution with nitric oxide (as diethylamine NONOate) enhanced poststorage functionality of an isolated working heart model.


METHODS
Excised hearts were ligated to an aortic cannula and immediately perfused retrogradely with oxygenated Krebs solution at a hydrostatic pressure 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 left atrial cannula at a filling pressure of 15 cm H2O. After a 1-minute stabilization period, baseline measurements of heart rate, aortic flow, coronary artery flow, and cardiac output were performed. Oxygenated cardioplegic solution (0.1 micromol/L), with or without NONOate, was then infused into the coronary 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 hemodynamic parameters measured after 12 hours storage and aortic flow at 6 hours storage compared with the untreated control groups. There was no significant difference between the water contents of the NONOate-treated and control groups.


CONCLUSIONS
The presence of the nitric oxide donor diethylamine NONOate was associated with significantly better preservation of coronary artery flow and cardiac function in the isolated rat heart after a 12-hour period of hypothermic storage and suggests a novel use for this family of compounds in the transplantation context.
Du
Z Y
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Cardiopulmonary Transplant Unit, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
Hicks
M
M
Jansz
P
P
Rainer
S
S
Spratt
P
P
Macdonald
P
P
D000818:Animals; D001011:Aorta / Q000502:physiology; D001783:Blood Flow Velocity; D002302:Cardiac Output; D002314:Cardioplegic Solutions; D003080:Cold Temperature; D006339:Heart Rate; D016027:Heart Transplantation; D006834:Hydrazines; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D009926:Organ Preservation; D051381:Rats; D017208:Rats, Wistar
D002314:Cardioplegic Solutions; D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine