MULTIPLE CYCLES OF PRECONDITIONING CAUSE LOSS OF PROTECTION IN OPEN-CHEST RABBITS

Although single or multiple bursts of ischemic preconditioning have be en shown to. protect against myocardial necrosis. the frequency-depend ency of the protection afforded by multiple stimuli has not yet been s ystematically studied in the anesthetized animal. The aim of the prese nt study was to characterize the effect of increasing numbers of preco nditioning stimuli (5 min ischemia plus 10 min reperfusion) in a colla teral-deficient species in vivo. Rabbits were anesthetized and divided into groups (n = 5-7/group) which were subjected to 0, 1, 2, 4, 6 or 8 cycles of preconditioning (each comprising 5 min of regional ischemi a plus 10 min reperfusion) followed by 45 min of regional ischemia and 2 h reperfusion. An additional group, serving as a control, was subje cted to eight cycles of preconditioning without a subsequent 45 min of regional ischemia. Infarct size (I) and risk zones (R) were delineate d with the aid of tetrazolium staining and fluorescent particles and t he I/R ratio was expressed as a percentage. Mean infarct size in the c ontrol group which had no preconditioning was 59.8 +/- 4.0%. This was reduced to 22.2 +/- 2.9%, 19.5 +/- 4.1% and 23.3 +/- 3.4% by one, two and four cycles of preconditioning. However, when the number of precon ditioning cycles was increased to six or eight protection declined wit h infarct sizes of 41.8 +/- 6.9% (P < 0.05 v zero preconditioning cont rol group) and 47.1 +/- 7.6% (N.S. v zero preconditioning control grou p). In the group subjected to eight cycles of preconditioning without subsequent ischemia, infarction was not detected. In conclusion, in th e anesthetized rabbit, beyond 4 cycles, protection against infarction diminishes with increasing numbers of preconditioning cycles. (C) 1997 Academic Press Limited.