"Preconditioning at a distance" in the isolated rabbit heart

Objective: Brief myocardial ischemia evokes a cardioprotective response, re ferred to as "ischemic preconditioning" (IP), that limits injury caused by a subsequent prolonged ischemic insult. The myocardial IP effect can be ind uced by ischemia of "distant" cardiac and noncardiac tissue, implicating th e involvement of an as-yet-unidentified humoral trigger. If a preconditioni ng hormone exists, the authors hypothesize that the IP effect should be tra nsferable, via administration of coronary effluent, from a preconditioned d onor heart to a virgin nonpreconditioned acceptor heart. Methods: Isolated buffer-perfused rabbit hearts were assigned to one of four treatment groups in a donor/acceptor sequence. Donor hearts underwent either three IP cycle s or a matched period of uninterrupted perfusion (control donors). Coronary perfusate collected from IP and control donor hearts was reoxygenated and transfused to virgin acceptor hearts. All hearts then underwent 30 minutes of global ischemia followed by 30 minutes of reperfusion. Left ventricular developed pressure (LVDP) (the authors' index of cardioprotection) was moni tored throughout the protocol by a left ventricular (LV) balloon. Results: In donor controls, LVDP assessed at 30 minutes post-reflow was restored to only 49 +/- 5% of baseline values. Recovery of LV function was significantl y enhanced in both IP donor hearts (69 +/- 4%*) and IP acceptor hearts (70 +/- 6%*) vs donor controls (*p , 0.05), while, in acceptor controls, interm ediate values of LVDP (62 +/- 7%) were obtained. Conclusion: The IP effect can be transferred between rabbit hearts, suggesting the presence of a humo ral trigger signal for distant :preconditioning. Isolating this hormone may have therapeutic and diagnostic implications in the management of acute my ocardial ischemia.