American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that has been shown to repress inflammatory gene expression in multiple cell types and diseases. However, little is known about the roles and mechanisms of ATF3 in liver ischemia/reperfusion injury (IRI). In warm and cold liver IRI models, we showed that ATF3 deficiency significantly increased ischemia/reperfusion (IR)-stressed liver injury, as evidenced by increased serum alanine aminotransferase levels, histological liver damage, and hepatocellular apoptosis. ⋯ Pretreatment of LPS-stimulated BMMs with M2 increased NRF2/HO-1 expression, promoted PI3K/AKT, which in turn suppressed TLR4/NF-κB-mediated proinflammatory mediators. Thus, our results first demonstrate ATF3-mediated NRF2/HO-1 signaling in the regulation of TLR4-driven inflammatory responses in IR-stressed livers. Our findings provide a rationale for a novel therapeutic strategy for managing IR-induced liver injury.
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Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty-one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. ⋯ One patient had primary nonfunction. Two combined pancreas-kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short-term outcomes.
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Case Reports
Dual temperature multi-organ recovery from a Maastricht category III donor after circulatory death.
Donation after circulatory death (DCD) makes a significant contribution to the transplant activity but is associated with significantly lower organ recovery rates and poorer function for the abdominal extra-renal organs compared with donation after brain death. Traditionally, DCD organ recovery involves cold thoracic and abdominal perfusion with a rapid removal of organs in order to minimize the ischemic damage. ⋯ We report a new technique for multi-organ recovery from Maastricht category III donors with abdominal normothermic perfusion and concomitant cold lung flushing which allows a rapid removal of the lungs with preservation of the abdominal normothermic circulation throughout the thoracic procurement. This approach could lead to an increased organ recovery and better function for the abdominal organs.