We have shown that a reverse-phase concentrate generated from the effluent of preconditioned (PC) rabbit hearts evokes a cardioprotective effect in virgin acceptor hearts. With the use of a model of sustained (1 h) simulated ischemia in isolated, spontaneously contracting rabbit jejunum, our current aims were to 1) determine whether protective factor(s) released from PC hearts can improve ischemic tolerance in noncardiac tissue; and 2) obtain preliminary insight into the mediator(s) involved in triggering and eliciting this remote protection. Recovery of contractile force following reoxygenation (our index of ischemic tolerance) was enhanced in jejunal segments pretreated with concentrate generated from PC hearts (33 +/- 3% of baseline, P < 0.01) versus segments that received no concentrate (21 +/- 2%) and segments treated with concentrate from normoxic hearts (16 +/- 3%; P < 0.01). Protection achieved with PC concentrate was attenuated by coadministration of naloxone or glibenclamide, thereby implicating the involvement of opioids and ATP-sensitive potassium channels. Moreover, evaluation of purified subfractions of the crude PC concentrate identified a specific bioactive fraction that may participate in triggering the improved jejunal ischemic tolerance.