ISCHEMIC PRECONDITIONING IN PIGS - A GRADED PHENOMENON - ITS RELATIONTO ADENOSINE AND BRADYKININ

Background-A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain th reshold, is an all-or-nothing or a graded phenomenon. Methods and Resu lts-In 71 enflurane-anesthetized swine, severe left anterior descendin g coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium c hloride) of 16.7+/-3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9+/-7.0%). IS was decreased to 9 .0+/-2.6% (P<0.05) by 3 minutes of IPc and reduced further to 1.9+/-0. 9% (P<0.05) by 10 minutes of IPc. The interstitial adenosine concentra tion (microdialysis, high-performance liquid chromatography) was uncha nged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573+/-144%). The interstitial bradykinin concentration (microdialy sis, radioimmunoassay) remained unchanged with 2 minutes of IPc but in creased to a similar extent with 3 minutes (by 198+/-32%) and 10 minut es (by 224+/-30%) of IPc. The IS reduction by 3 minutes of IPc was abo lished by blockade of the bradykinin B-2 receptor with intracoronary H OE 140 (16.6+/-4.3%) but not with intracoronary infusion of adenosine deaminase (8.4+/-2.5%, P<0.05). HOE 140, however, did not affect the I S reduction (3.5+/-1.1%, P<0.05) by 10 minutes of IPc. Combined infusi on of HOE 140 and adenosine deaminase abolished the IS reduction by 10 minutes of IPc (15.4+/-6.7%). Conclusions-IS reduction by IPc is a gr aded phenomenon. Whereas bradykinin is essential during preconditionin g ischemia of shorter duration, adenosine is more important during pre conditioning ischemia of longer duration.