Rabbit heart can be "preconditioned" via transfer of coronary effluent

Brief myocardial ischemia not only evokes a local cardioprotective or "prec onditioning" effect but also can render remote myocardium resistant to sust ained ischemia. We propose the following hypotheses: remote protection is i nitiated by a humoral trigger; brief ischemia-reperfusion will result in re lease of the humoral trigger (possibly adenosine and/or norepinephrine) int o the coronary effluent; and transfer df this effluent to a virgin acceptor heart will elicit cardioprotection. To test these concepts, effluent was c ollected during normal perfusion from donor-control hearts and during preco nditioning ischemia-reperfusion from donor-preconditioned (PC) hearts. Afte r reoxygenation occurred and aliquots for measurement of adenosine and nore pinephrine content were harvested, effluent was transfused to acceptor-cont rol and acceptor-PC hearts. All hearts then underwent 40 min of global isch emia and 60 min of reperfusion, and infarct size was delineated by tetrazol ium staining. Mean infarct size was smaller in both donor- and acceptor-PC groups (9% of left ventricle) than in donor- and acceptor-control groups (3 6% and 34%; P < 0.01). Protection in acceptor-PC hearts could not, however, be attributed to adenosine or norepinephrine. Thus preconditioning-induced cardioprotection can be transferred between rabbit hearts by transfusion o f coronary effluent. Although adenosine and norepinephrine are apparently n ot responsible, these results suggest that remote protection is initiated b y a humoral mechanism.