ABSTRACT The goal of this project is to establish routinely successful prolonged normothermic ex vivo heart perfusion (NEVHP) leading to organ banks. We have demonstrated routinely successful ex vivo heart perfusion for 24-72 hours using plasma exchange with a paracorporeal animal, then fresh plasma alone, then continuous hemofiltration in sheep and pigs. The experiments proposed in this application are planned to determine the factors responsible for prolonged NEVHP and demonstrate routine 3-day successful ex vivo perfusion. This would allow heart treatment, verifying heart function, near perfect matching, increase donors, and make heart transplantation elective. In addition, the NEVHP protocols and systems will be tested to resuscitate hearts after prolonged periods of cold ischemia and hearts from DCD. Critical step prior translated the animal models into clinical practice. Lessons from the research with hearts will apply to other organs.