Does ischemic preconditioning require reperfusion before index ischemia?

Background: Ischemic preconditioning (IP) is initiated through one or sever al short bouts of ischemia and reperfusion which precede a prolonged ischem ia. To test whether a reperfusion must precede the prolonged index ischemia , a series without reperfusion (intraischemic preconditioning: lip) and a s eries with gradual onset of ischemia, i.e. ramp ischemia (RI), which is pos sibly related to the development of hibernation, was compared to convention al IP (CIP). Method: Experiments were performed an 27 blood-perfused rabbit hearts (Langendorff apparatus) that were randomized into one of four serie s: (1) control (n = 7): 60 min normal flow --> 60 min tow flow (10%) ischem ia --> 60 min reperfusion. (2) CIP (n = 7): 4 times 5 min zero flow with 10 min reperfusion each --> 60 min low flow (10%) --> ischemia 60 min reperfu sion. (3) IIP (n = 7): 50 min normal flow --> 10 min no flow --> 60 min low flow (10%) ischemia --> 60 min reperfusion. (4) RI (n = 6): gradual reduct ion to 10% flow during 60 min --> 60 min low flow (10%) ischemia --> 60 min reperfusion. At the end of each protocol, the infarcted area was assessed. Results: The infarct area in control hearts was 6.7 +/- 1.4% (means +/- SE M) of LV total area, in CIP hearts 2.6 +/- 0.8%, in IIP hearts 3.1 +/- 0.5% , and in RI hearts 3.0 +/- 0.3% (all p < 0.05 vs. control). The differences between the three protection protocols were statistically not significant, and no protective protocol reduced post-ischemic myocardial dysfunction. C onclusion: The preconditioning effect (infarct size reduction) appears not to depend on intermittent reperfusion. Thus, the protective mechanism of IP develops during the initial ischemia that precedes the index ischemia. Alt ernatively, low-flow ischemia is effectively a sort of reperfusion.