The invention provides methods for treating ischemia (such as ischemia repertusion injury (IRI)) in tissue (such as transplant donor tissue), comprising contacting the tissue during ex vivo perfusion with a therapeutically effective amount of RNAi (such as siRNA) that specifically hinds to at least a portion of a gene (such as p53) that mediates ischemic injury in the tissue. The invention's methods additionally decrease the risk of tissue rejection and/or or induce immunological tolerance to transplanted tissue.