Protection from preconditioning can be reinstated at various reperfusion intervals

Abstract

The aim of this study was to evaluate the way in which short-term protection declines and is eventually lost in preconditioning and to determine the efficacy of a second preconditioning at various reperfusion intervals. Male rabbits were divided into six groups. Forty-five minutes (sustained) ischemia followed by 120 minutes reperfusion was applied 60, 65, 70, 75, and 80 minutes after a 5 minute preconditioning (groups A, B, C, D, and E) and in a control group (F) after no preconditioning. The infarct to risk ratio (I/R) was 38.3 +/- 3.5% in group A, 46.0 +/- 7.8% in B, 61.6 +/- 9.7% in C, 68.1 +/- 4.2% in D, 64.5 +/- 7.8% in E, and 61.0 +/- 7.7% in F. Group A had a smaller I/R compared with groups C, D, E, and F (p < 0.05). In another series, groups G, H, and I were exposed to two 5-minute preconditioning stimuli, separated, respectively, by 45, 60, and 75 minutes of reperfusion; 10 minutes after the last preconditioning, the animals were exposed to 45-minutes ischemia and 120 minutes reperfusion. Groups A and D (with the smaller and higher I/R ratio) were also incorporated into this protocol in order to compare the effect of the additional preconditioning with the single one. The I/R ratio was 25.4 +/- 8.5% in group G, 22.8 +/- 7.0% in group H, and 14.7 +/- 4.0% in group I (p = NS). Group D showed a higher I/R compared with groups G, A, and H (p < 0.01), and group I had a smaller I/R compared with groups A (p < 0.01) and D (p < 0.001). Cardioprotection after a first preconditioning declines gradually and is eventually lost. An additional preconditioning is always effective, and the longer the interval from the first preconditioning, the more potent is the effect.