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脑死亡供体复苏期间常温局部灌注对肺移植功能的影响:一项临床前研究。

Impact of normothermic regional perfusion during DCD recovery on lung allograft function: A preclinical study.

作者信息

Ribeiro Rafaela V P, Reynolds Frank A, Sarrafian Tiffany L, Spadaccio Cristiano, Colby Clint, Richman Adam, Brazzell Jennifer L, Ergi Defne Gunes, Altarabsheh Salah, Daxon Benjamin T, Cypel Marcelo, Saddoughi Sahar A

机构信息

Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Department of Cardiovascular Perfusion, Mayo Clinic, Rochester, Minnesota.

出版信息

JHLT Open. 2023 Oct 26;2:100009. doi: 10.1016/j.jhlto.2023.100009. eCollection 2023 Dec.

Abstract

BACKGROUND

Normothermic regional perfusion (NRP) has been growing as a novel procurement strategy after circulatory death (donation after circulatory death (DCD)) in the context of heart transplantation. However, the impact of NRP on lung graft viability is largely unknown. We sought to determine lung function after thoraco-abdominal NRP (TA-NRP) in a clinically relevant porcine DCD model.

METHODS

Donor domestic pigs underwent hypoxic cardiac arrest to simulate DCD procurement and were randomly allocated to either 1-hour resuscitation on TA-NRP ( = 4) or direct lung procurement (direct procurement and perfusion (DPP),  = 4). All lungs were placed on ex-vivo lung perfusion (EVLP) and evaluated for 3 hours to assess functional outcome parameters and suitability for transplantation.

RESULTS

After 1 hour of TA-NRP, cardiopulmonary bypass was weaned, and mean systemic PaO/fraction of inspired oxygen was 418 ± 76 mm Hg, which was comparable to baseline (467 ± 41,  = 0.41). No significant differences were seen between the groups during EVLP, except for a higher pulmonary artery pressure in the TA-NRP group at 3 hours of EVLP (19.7 ± 1.5 vs 14.7 ± 2.1 mm Hg,  = 0.02). Perfusate inflammatory cytokines levels of IL-6 and IL-8 were higher at the first hour of EVLP in the TA-NRP group; however, these differences were not sustained as levels were similar by the last hour of EVLP. There were no differences in histology, cytokines, or metabolic profile of the TA-NRP lungs compared to DPP.

CONCLUSIONS

TA-NRP porcine lungs met functional criteria to proceed to transplantation and demonstrated no significant histological, cytokine, and metabolic differences when compared to DPP porcine lungs. This study highlights the value of considering TA-NRP lungs for transplant with well-established protocols.

摘要

背景

在心脏移植领域,常温区域灌注(NRP)作为一种循环死亡后(心脏死亡后捐献,DCD)的新型获取策略正在逐渐兴起。然而,NRP对肺移植供体肺存活能力的影响在很大程度上尚不清楚。我们试图在一个具有临床相关性的猪DCD模型中确定胸腹常温区域灌注(TA-NRP)后的肺功能。

方法

供体家猪经历缺氧性心脏骤停以模拟DCD获取过程,并被随机分配至TA-NRP组进行1小时复苏(n = 4)或直接肺获取组(直接获取与灌注,DPP,n = 4)。所有肺均置于体外肺灌注(EVLP)中,并评估3小时以评估功能结局参数及移植适宜性。

结果

TA-NRP 1小时后,体外循环撤离,平均体循环动脉血氧分压/吸入氧分数为418±76 mmHg,与基线水平(467±41,P = 0.41)相当。在EVLP期间,两组间未见显著差异,但在EVLP 3小时时TA-NRP组肺动脉压较高(19.7±1.5 vs 14.7±2.1 mmHg,P = 0.02)。在EVLP第1小时,TA-NRP组灌注液中白细胞介素-6(IL-6)和白细胞介素-8(IL-8)等炎性细胞因子水平较高;然而,这些差异在EVLP最后1小时并不持续,因为此时水平相似。与DPP组相比,TA-NRP组肺在组织学、细胞因子或代谢谱方面无差异。

结论

TA-NRP猪肺符合进行移植的功能标准,与DPP猪肺相比,在组织学、细胞因子及代谢方面无显著差异。本研究强调了采用成熟方案考虑将TA-NRP肺用于移植的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8635/11935417/77f7106b78fc/gr1.jpg

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