急性肺移植排斥反应患者外周血管中内皮介导的血管舒张功能受损。

Impaired endothelium-mediated vasodilatation in the peripheral vasculature of patients with acute pulmonary allograft rejection.

作者信息

Scherstén H, Kirnö K, Ekroth R, Lundin S, Pettersson A, Kjellström C, Miller V M, Nilsson F

机构信息

Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.

出版信息

J Heart Lung Transplant. 1996 Jun;15(6):556-63.

PMID:8803752

Abstract

BACKGROUND

Experimental studies have provided evidence that, during acute pulmonary allograft rejection, endothelial dysfunction occurs not only in the transplanted lung but also in arteries of organs native to the transplant recipient. We therefore tested the hypothesis that allograft rejection leads to the release of factors into the circulation that could affect the endothelial function in lung transplant recipients.

METHODS

Acetylcholine (10, 30, and 60 micrograms/min) and sodium nitroprusside (1, 3, and 6 micrograms/min) were infused into the brachial artery in nine transplant recipients (five single lung, one double lung, three heart-lung) 2 to 37 weeks after transplantation, during both acute rejection and rejection-free episodes. Changes in forearm blood flow were assessed with venous occlusion plethysmography. Plasma levels of interleukin-2, -6, and -8, endothelin-1, L-arginine, and asymmetric dimethylarginine were measured and correlated to rejection episodes.

RESULTS

The vasodilatory response to acetylcholine was significantly reduced during acute rejection compared with rejection-free episodes (percentage increase from basal flow: 156% +/- 21%, 395% +/- 65%, and 585% +/- 87% during rejection versus 272% +/- 75%, 633% +/- 113%, and 933% +/- 158% during absence of rejection, p < 0.05). No statistically significant difference was found between vasodilatory responses to nitroprusside during acute rejection and rejection-free episodes. Plasma levels of L-arginine, asymmetric dimethylarginine, interleukin-6, and endothelin-1 were not significantly altered during lung rejection.

CONCLUSIONS

These data indicate that a reversible peripheral decrease in endothelium-dependent vasodilatation occurs during acute rejection in lung transplant recipients. This result may be due to interactions among circulating cytokines and leukocytes activated by the rejection process and the endothelium.

摘要

背景

实验研究已提供证据表明，在急性肺移植排斥反应期间，内皮功能障碍不仅发生在移植肺中，也发生在移植受者的原生器官动脉中。因此，我们检验了以下假设：同种异体移植排斥反应会导致因子释放到循环中，从而可能影响肺移植受者的内皮功能。

方法

在9名移植受者（5名单肺移植、1名双肺移植、3名心肺移植）移植后2至37周，于急性排斥反应期和无排斥反应期，将乙酰胆碱（10、30和60微克/分钟）和硝普钠（1、3和6微克/分钟）注入肱动脉。用静脉阻塞体积描记法评估前臂血流量变化。测量血浆白细胞介素-2、-6和-8、内皮素-1、L-精氨酸和不对称二甲基精氨酸水平，并与排斥反应发作相关联。

结果

与无排斥反应期相比，急性排斥反应期间对乙酰胆碱的血管舒张反应显著降低（排斥反应期间基础血流量增加百分比：156%±21%、395%±65%和585%±87%，无排斥反应期间为272%±75%、633%±113%和933%±158%，p<0.05）。急性排斥反应期和无排斥反应期对硝普钠的血管舒张反应之间未发现统计学显著差异。肺排斥反应期间，L-精氨酸、不对称二甲基精氨酸、白细胞介素-6和内皮素-1的血浆水平无显著改变。