Abstract 385: Amelioration of Heart Transplantation-Induced Ischemia-Reperfusion Injury by Melatonin and Ghrelin in Rats
Background: Global myocardial ischemia reperfusion (I/R), which is often obligatory during cardiac surgery, induce an inflammatory response in the transplanted heart. Inflammatory reactions in the graft have a pivotal influence on acute as well as long term graft function.
Objective: This study was undertaken to investigate the potential role of melatonin and ghrelin in amelioration of I/R injury in the transplanted heart in rat model.
Materials and Methods: The rats were randomized into 4 equal groups. Group 1 sham group, rat underwent the same anesthetic and surgical procedure as the control group except for heterotopic heart transplantation, group 2 control group, rats underwent heterotopic heart transplantation and subjected to global ischemia for 30 min and reperfusion for 2 hours, group 3 donor and recipient rats received melatonin 10 mg/kg i.p. 30 min before the transplant procedure and the same dose at the reperfusion, group 4 donor and recipient rats received ghrelin 10-8 mol/kg i.p. ( 2 doses) 13 & 1 hour before the transplant procedure, the heterotopic heart transplantation is done using the cuff technique in the neck ( the aorta of the donor is anastomosed with the carotid artery of the recipient and the pulmonary artery of the donor to the jugular vein of the recipient). At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I(cTn I). The heart were harvested, the apical side was fixed in 10% formalin for histological examination and the basal side was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and intracellular adhesion molecule-1 (ICAM-1).
Results: Compared with the sham group, levels of myocardial TNF-α & IL-1β, and ICAM-1; plasma cTn I were increased (p<0.05), Histologically, all induced untreated rats showed significant myocardial injury (P < 0.05) Both melatonin and ghrelin significantly counteract the increase in myocardium level of TNF-α, IL-1, & ICAM-1 (P < 0.05). histological analysis revealed that both melatonin and ghrelin markedly reduced (P < 0.05) the severity of heart injury in the rats underwent transplant procedure.
Conclusion: The results of the present study reveal that melatonin and ghrelin may ameliorate I/R injury in the grafted heart in rats via interfering with inflammatory reactions which induced by I/R injury . These findings suggested that both melatonin and ghrelin have a promising graft protective effect against transplant induced global I/R injury.
- © 2012 by American Heart Association, Inc.