Andrijevic D, Vrselja Z, Lysyy T, et al. Cellular recovery after prolonged warm ischaemia of the whole body. Nature 2022;608(7922):405–412. Irreversible organ injury following prolonged ischemia is a critical problem in organ transplantation. Demand for organs continues to exceed supply, so interventions that increase the number of organs available for transplantation are critically needed. Different techniques have been developed to rescue tissues after ischemia. BrainEx technology is one such technology, with a demonstrated capacity to rescue brain circulation after death. This study focuses on OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. The perfusion solution of OrganEx contains pharmacologic suppressors of cell death. The investigators compared the perfusion efficiency of OrganEx with extracorporeal membrane oxygenation system (ECMO), which is used for whole-body perfusion in patients with inability to oxygenate appropriately when in cardiogenic shock or respiratory failure. After cardiac arrest and cessation of systemic circulation in a porcine model, warm ischemia injury was induced for 1 hour followed by 6 hours of perfusion under hypothermic conditions with either ECMO or OrganEx. The porcine model perfused with the use of OrganEx showed circulation reinstatement and restoration of physiologic and metabolic parameters at a whole-body scale compared with the ECMO system. Examination of the brain tissue, the organ most susceptible to ischemia, showed minimal cytotoxic edema and preservation of cellular and tissue integrity with the use of OrganEx compared with ECMO group. Similarly, the heart, lungs, liver, kidneys, and pancreas revealed absence of injury and cytoarchitectural damage with the use of OrganEx. In addition, metabolic and functional activity of highly metabolic organs was preserved in the OrganEx group. Consistent with this, single-nucleus transcriptomic profiling on different tissues in the OrganEx group showed significant enrichment of gene sets involved in cytoskeletal assembly, DNA repair, ATP metabolism, and suppression of cell death–associated pathways. Overall, OrganEx technology represents an important development in the field of whole-body recovery after ischemia, with evidence of restored metabolism at the molecular level. This technology has the potential to significantly increase the availability of organs for transplantation by extending the limits of allowable warm ischemia times as well as to improve outcomes in patients with cardiovascular events. Future studies in the human context are needed to confirm and fulfill this potential.