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Background <p>Ex vivo lung perfusion (EVLP) is pivotal for assessing and preserving marginal donor lungs. While red-blood-cell (RBC)-based perfusates enhance oxygen delivery, they increase pulmonary vascular resistance, thereby potentially exacerbating perfusion-induced injury. This study compared a novel acellular oxygen carrier, PEGylated bovine hemoglobin (PEG-bHb), against RBC-based and acellular perfusates in a rat EVLP-transplantation model.</p> Methods <p>A total of 49 rats were included in this study. Lungs underwent 4&#xa0;h EVLP with acellular, RBC or PEG-bHb solutions, followed by left-lung transplantation and 2&#xa0;h reperfusion; unperfused lungs served as controls. Respiratory mechanics, gas exchange, inflammatory cytokines, oxidative-stress markers, tight junction integrity (Occludin), and histology were evaluated. Bulk RNA-sequencing, qRT-PCR, and immunofluorescence for endoplasmic reticulum (ER) stress markers (ATF-6, ATF-4, CHOP and ubiquitin) were employed to explore underlying mechanisms.</p> Results <p>PEG-bHb demonstrated lower pulmonary vascular resistance and higher dynamic compliance than the RBC group. Inflammatory cytokine (IL-6, IL-1β, TNF-α) and Oxidative markers (MDA, HIF-1α) in lung tissue were reduced compared to acellular and RBC groups. Occludin expression indicated superior alveolar–capillary integrity versus control and acellular groups and parity with RBC group. Post-transplantation, the PEG-bHb group exhibited the least histological injury and the highest IL-10 expression, indicating attenuated early graft damage. Transcriptomic analysis suggested concurrent regulation of endoplasmic-reticulum stress and cytokine pathways; immunofluorescence demonstrated reduced ATF-6, increased ATF-4, and stable CHOP expression.</p> Conclusion <p>PEG-bHb reduced early post-transplant injury by preserving lung compliance, sustaining barrier integrity, and mitigating inflammatory stress during EVLP. It represents a promising candidate for clinical EVLP application.</p> Graphical Abstract <p></p>

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Comparative evaluation of PEGylated bovine hemoglobin as a perfusate in rat ex vivo lung perfusion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Jie Zhang,
  • Xuanlin Zhang,
  • Haoxiang Yuan,
  • Jingfeng Ou,
  • Guanyi Wu,
  • Jianxing He

摘要

Background

Ex vivo lung perfusion (EVLP) is pivotal for assessing and preserving marginal donor lungs. While red-blood-cell (RBC)-based perfusates enhance oxygen delivery, they increase pulmonary vascular resistance, thereby potentially exacerbating perfusion-induced injury. This study compared a novel acellular oxygen carrier, PEGylated bovine hemoglobin (PEG-bHb), against RBC-based and acellular perfusates in a rat EVLP-transplantation model.

Methods

A total of 49 rats were included in this study. Lungs underwent 4 h EVLP with acellular, RBC or PEG-bHb solutions, followed by left-lung transplantation and 2 h reperfusion; unperfused lungs served as controls. Respiratory mechanics, gas exchange, inflammatory cytokines, oxidative-stress markers, tight junction integrity (Occludin), and histology were evaluated. Bulk RNA-sequencing, qRT-PCR, and immunofluorescence for endoplasmic reticulum (ER) stress markers (ATF-6, ATF-4, CHOP and ubiquitin) were employed to explore underlying mechanisms.

Results

PEG-bHb demonstrated lower pulmonary vascular resistance and higher dynamic compliance than the RBC group. Inflammatory cytokine (IL-6, IL-1β, TNF-α) and Oxidative markers (MDA, HIF-1α) in lung tissue were reduced compared to acellular and RBC groups. Occludin expression indicated superior alveolar–capillary integrity versus control and acellular groups and parity with RBC group. Post-transplantation, the PEG-bHb group exhibited the least histological injury and the highest IL-10 expression, indicating attenuated early graft damage. Transcriptomic analysis suggested concurrent regulation of endoplasmic-reticulum stress and cytokine pathways; immunofluorescence demonstrated reduced ATF-6, increased ATF-4, and stable CHOP expression.

Conclusion

PEG-bHb reduced early post-transplant injury by preserving lung compliance, sustaining barrier integrity, and mitigating inflammatory stress during EVLP. It represents a promising candidate for clinical EVLP application.

Graphical Abstract