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