Mild Permissive Alkalosis Improves Outcomes in Porcine Negative Pressure Ventilation Ex-Situ Lung Perfusion

IF 0.8 4区医学 Q4 IMMUNOLOGY

Transplantation proceedings Pub Date : 2024-12-01 DOI:10.1016/j.transproceed.2024.10.031

Keir Forgie , Abeline Watkins , Katie Du , Alynne Ribano , Nicholas Fialka , Sayed Himmat , Sanaz Hatami , Mubashir Khan , Xiuhua Wang , Ryan Edgar , Katie-Marie Buswell-Zuk , Darren H. Freed , Jayan Nagendran

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引用次数: 0

Abstract

Background

Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N₂/O₂/CO₂) or pure sweep gas (CO₂) to target venous blood gas composition with physiologic pCO₂ and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines. Increased hydrostatic pressure worsens edema and lung function. We report improved ESLP outcomes using mild permissive alkalosis.

Methods

Twelve juvenile pig lungs underwent 12-hour Negative Pressure Ventilation (NPV)-ESLP with a physiologic pH (Control: pH 7.35-7.45, n=6) or mild permissive alkalosis (pH+: pH 7.45-7.55, n=6) by varying sweep CO₂ delivery. Three left lungs per group were transplanted and assessed over 4-hours.

Results

Five Control lungs failed on ESLP due to high PAPs, low compliance, and poor oxygenation. Repeat Controls (n=6) were performed to attain 12-hours of ESLP. There were no failures in the pH+ group. Results are pH+ vs Control. Oxygenation (PaO₂/FiO₂ 454.2 vs 438.2; P = .37) and dynamic compliance (21.38 vs 22.22 mL/cmH₂O; P = .41) were stable over 12-hour NPV-ESLP. Mean evaluation pH/pCO₂/HCO₃^- was 7.50/15.6/14.5 vs 7.41/38.7/24.7. Control lungs required repeat THAM and milrinone boluses on ESLP to prevent acidosis and treat elevated PVR; this was not necessary in the pH+ group. Weight-gain/hour was similar (1.23% vs 1.38%; P = .37). Mean left lung PF ratios 4-hours post-transplantation were 301 mmHg vs 196 mmHg (P = .11). Control TNF-⍺ and IL-6 perfusate concentrations were significantly greater.

Conclusions

Mild permissive alkalosis porcine NPV-ESLP demonstrated more reliable preservation with reduced inflammation compared to a physiologic pH strategy.

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轻度容许性碱中毒改善猪负压通气非原位肺灌注的预后。

背景：体外肺灌注（exsitu Lung Perfusion， ESLP）采用膜式除氧器和混合（N2/O2/CO2）或纯扫气（CO2），以生理pCO2和ph为靶点，靶向静脉血气体组成。临床上，轻度容许性碱中毒可抵消肺血管阻力（PVR）升高，改善灌注。ESLP期间PVR和肺动脉压（PAP）升高反映了促炎细胞因子升高。静水压力增加会加重水肿和肺功能。我们报告轻度容许性碱中毒可改善ESLP结果。方法：对12只幼年猪肺进行12小时负压通气(NPV)-ESLP，通过不同的扫气量CO2输送，使其处于生理pH（对照：pH 7.35-7.45, n=6）或轻度容许性碱中毒（pH+: pH 7.45-7.55, n=6）。每组移植3个左肺，随访4小时。结果：5个对照肺因pap高、依从性低、氧合不良而衰竭。重复对照组（n=6）达到12小时的ESLP。pH+组无失败。结果是pH+ vs对照。氧合(PaO2/FiO2 454.2 vs 438.2；P = 0.37)和动态顺应性(21.38 vs 22.22 mL/cmH2O；P = .41)在NPV-ESLP 12小时内稳定。平均评价pH/pCO2/HCO3-为7.50/15.6/14.5 vs 7.41/38.7/24.7。控制肺需要在ESLP上重复使用THAM和米力农，以防止酸中毒和治疗PVR升高；这在pH+组中是不必要的。体重增加/小时相似(1.23% vs 1.38%；P = .37)。移植后4小时平均左肺PF比值为301 mmHg vs 196 mmHg （P = 0.11）。对照组TNF-和IL-6灌注液浓度显著升高。结论：与生理性pH策略相比，轻度容许性碱中毒猪NPV-ESLP表现出更可靠的保存和减少炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation proceedings 医学-免疫学

CiteScore

1.70

自引率

0.00%

发文量

502

审稿时长

60 days

期刊介绍： Transplantation Proceedings publishes several different categories of manuscripts, all of which undergo extensive peer review by recognized authorities in the field prior to their acceptance for publication. The first type of manuscripts consists of sets of papers providing an in-depth expression of the current state of the art in various rapidly developing components of world transplantation biology and medicine. These manuscripts emanate from congresses of the affiliated transplantation societies, from Symposia sponsored by the Societies, as well as special Conferences and Workshops covering related topics. Transplantation Proceedings also publishes several special sections including publication of Clinical Transplantation Proceedings, being rapid original contributions of preclinical and clinical experiences. These manuscripts undergo review by members of the Editorial Board. Original basic or clinical science articles, clinical trials and case studies can be submitted to the journal?s open access companion title Transplantation Reports.