Protective Effect Of Endothelin-receptor Antagonist PD142893 On Early Ischemia-Reperfusion Injury In Rats Lung Allotransplantation

PartⅠImprovements of surgical technique in establishment of rat orthotopic pulmonary transplantation model using cuffs.Objective: To establish more simple and effective rat orthotopic lung transplantation model. Methods: Twenty rats were randomly divided into donor and recipient groups. Rat lung transplantation model were established by using improved cuff technique. Results: All the ten operations were accomplished successfully. The mean operative time of recipient was (45±4) min. All 10 rats were survived over 30 days after lung transplantation. Check of X-ray was almost normal and there was no significant difference in the blood gas analysis before and after clipping the right hilum at 30th post operation day. Conclusion: This method is more simple, applicable and requires less time. We may use it in establishing rat lung transplantation model.PartⅡProtective effect of endothelin-receptor antagonist PD142893 on early Ischemia-Reperfusion Injury in rats lung allotransplantation.Objective: To study the influence and mechanism of endothelin-1 (ET-1)-receptor antagonist PD142893 treatment on lung ischemia–reperfusion injury. Methods: Sixty Rats were subjected to left lung allotransplantation and randomly divided into two groups. The treatment group (n=30) received an intravenous infusion of ET-receptor antagonist PD142893(0.1mg/kg) 0.5ml, five minutes before unclamping the hemostat. The control group received NS. At 0h, 1h, 2h, 6h, 12h and 24h after transplantation, animals were anesthetized to obtain sample. The left pulmonary venous blood gas, plasma ET-1 and IL-6 were detected. The pathologic condition of transplanted lung was observed and apoptosis was detected by TUNNEL. Lung wet-to-dry-weight ratio was also detected. Results: The pulmonary venous oxygen tension were of no difference between the two groups at 0h and 24h, at the other time , the treatment group were higher(P<0.05). The plasma IL-6 concentrations of treatment group were higher than the control group at each time except 0h(P<0.05). The plasma ET-1 concentrations were higher in the treatment group(P<0.05). Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control group. The alveolar space had obvious exudation. Histology of the treatment group were mild. Apoptosis index and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals(P<0.05). Conclusion: Treatment of lung allograft with the mixed endothelin A/endothelin B receptor antagonist PD142893 can ameliorate ischemia-reperfusion injury which is related to moderating lung interstitial edema and inhibition of inflammatory reaction.