Naloxone blocks transferred preconditioning in isolated rabbit hearts

We have shown that the cardioprotective benefits of ischemic preconditionin g (PC) can be transferred from PC to virgin acceptor hearts via coronary ef fluent transfusion, implicating the presence of hormonal preconditioning fa ctor(s). Using isolated buffer-perfused rabbit hearts, our aims were to: (1 ) determine whether the protective factor(s) could be concentrated and reco vered by reverse phase chromatography and (2) whether opioid receptor activ ation contributes to this transferred cardioprotection. Material released i nto the coronary effluent during PC ischemia/reperfusion or normoxic perfus ion was concentrated by reverse phase chromatography. In phase one, hearts received no intervention (controls), PC ischemia, concentrate generated fro m normoxic hearts (normoxic acceptors) or concentrate from PC hearts (PC ac ceptors). All hearts underwent 40 min of global ischemia, and area of necro sis (AN) was delineated by tetrazolium staining. In phase two, three additi onal groups of hearts (control, PC and PC acceptors) received the opioid an tagonist naloxone (2 pm) throughout the intervention phase. Treatment with normoxic concentrate had no effect on infarct size: (AN: normoxic acceptors 39 +/- 8%; control 42 +/- 8%). In contrast, treatment with PC concentrate evoked cardioprotection equivalent to that afforded by conventional PC (AN 19 +/- 5% and 21 +/- 6% respectively: P <0.05 v control). Naloxone had no e ffect on infarct size in controls, and did not inhibit preconditioning. How ever, naloxone abrogated the protection achieved by transfer of PC concentr ate (AN: 44 +/- 7%). These results indicate that PC concentrate evokes a ca rdioprotective effect via a mechanism requiring an intact opioid receptor s ystem. (C) 2001 Academic Press.