Ischemic preconditioning produces systemic protective and adoptively transferable effects

Abstract

Ischemic preconditioning directly protects organs from subsequent non-specific injuries. To test for systemic protective effects kidneys from F-344 donor rats went through a short warm ischemic time. Both, clamped and contralateral unclamped kidneys were procured after either a short (15 min) or long (24 h) reperfusion period and transplanted into Lewis rats following a prolonged cold ischemia. To test for transferable effects serum from preconditioned rats was infused either into native donors or recipients. Following a short reperfusion interval protective effects were only evident in previously clamped grafts. However, after a long reperfusion interval protective effects were observed in previously clamped and contralateral unclamped kidneys promoting improved survival, structure, function and reduced inflammation. These effects were not related to heme oxygenase-1 induction or neural transmission as heme oxygenase-1 inhibition or denervation prior to preconditioning did not affect organ protection. These results show that renal ischemic preconditioning is associated with time-dependent local and systemically transferable protection.