Mechanisms and strategies for organ recovery

Abstract

Oxygen is essential for the viability of mammalian cells. Disruptions in circulation lead to a cessation of oxygen delivery, which causes decreased ATP production, intracellular acidosis and oedema. If blood flow is reintroduced, this initiates secondary cellular damage usually facilitating cell death. Nonetheless, such outcomes are not inevitable; cells from various organs have been recovered in vitro after extended periods without blood supply, with emerging technologies aimed at scaling up these findings. Perfusion systems, inspired by heart–lung machines, provide mechanical support by restoring circulation, regulating temperature, exchanging gases and modifying circulating perfusate with various pharmacological compounds. Together, perfusion systems and perfusates have mitigated cellular demise and recovered injured tissues, potentially revolutionizing resuscitation medicine and organ transplantation. This Review summarizes the biological mechanisms of cellular injury, perfusate modifications and mechanistic approaches for reinstating circulation, and offers perspectives on the future of organ and whole-body recovery. Emerging perfusion technologies restore circulation and mitigate cell damage post ischaemia and reperfusion, showing promise for resuscitation medicine and organ transplantation. This Review explores cellular injury mechanisms, machine perfusion approaches and perfusate modifications for organ and whole-body recovery following circulatory cessation.