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远程缺血预处理在肺移植患者中的安全性、可行性和效果。

Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation.

机构信息

Department of Anaesthesia and Perioperative Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.

Department of Allergy Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.

出版信息

J Heart Lung Transplant. 2014 Nov;33(11):1139-48. doi: 10.1016/j.healun.2014.04.022. Epub 2014 May 9.

Abstract

BACKGROUND

Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation.

METHODS

A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups.

RESULTS

No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC.

CONCLUSIONS

RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.

摘要

背景

原发性移植物功能障碍(PGD)仍是肺移植后的一个重大问题。来自动物和临床研究的数据表明,远程缺血预处理(RIC)可能减轻实体器官移植中的缺血再灌注损伤。

方法

一项针对 60 例双侧序贯肺移植患者的初步随机对照试验评估了 RIC 减轻 PGD 的效果。治疗组患者在供体再灌注前进行 3 个周期的下肢缺血预处理。主要观察指标是治疗组间动脉血氧分压/吸入氧分数比值(P/F 比值)的比较。

结果

未观察到止血带应用的不良反应。移植后 24 小时内,治疗组的平均最低 P/F 比值为 271.3mmHg,对照组为 256.1mmHg(p=0.46)。PGD 分级和严重程度以及急性排斥反应的发生率也倾向于治疗组。亚组分析表明,RIC 对以限制性肺疾病为主要诊断的患者有显著获益,这组患者发生 PGD 的风险较高。RIC 不伴有高迁移率族蛋白框 1 的全身释放。细胞因子、高迁移率族蛋白框 1 和内源性晚期糖基化终产物受体的水平在再灌注后 2 小时内达到峰值,可能反映了供体器官的质量,而不是 RIC 的影响。

结论

在这项随机对照试验中,RIC 并未显著改善 P/F 比值或 PGD。然而,这项小研究中的令人鼓舞的结果表明,RIC 在肺移植中需要进行更大规模的多中心试验。

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