After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death^1,2. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology³. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.

血流停止或类似的缺血暴露后，有害的分子级联反应在哺乳动物细胞中开始，最终导致它们死亡^1,2。然而，通过有针对性的干预，这些过程甚至可以在死后几分钟或几小时内得到缓解或逆转，正如使用 BrainEx 技术在离体猪脑中所报告的那样³. 迄今为止，将单器官干预转化为完整的全身应用仍然受到循环和多系统生理挑战的阻碍。在这里，我们描述了 OrganEx，它是 BrainEx 体外脉动灌注系统和用于猪全身环境的细胞保护灌注液的改编版。在热缺血 1 小时后，应用 OrganEx 可保持组织完整性，减少细胞死亡并恢复多个重要器官的选定分子和细胞过程。相应地，单核转录组学分析揭示了器官和细胞类型特异性的基因表达模式，这些模式反映了特定的分子和细胞修复过程。我们的分析包括在定义的缺血间隔和跨越多个器官的灌注干预期间细胞类型特异性变化的综合资源，