F019 Postconditioning still beneficial if applied 30 minutes after the onset of reperfusion in mice

Abstract

Brief intermittent episodes of ischemia and reperfusion applied at the onset of reperfusion after a prolonged period ischemia confer cardioprotection, a phenomenon termed postconditioning (postC). The aim of our study was to study the time window of protection offered by postconditioning in mice submitted to ischemia/reperfusion-injury. 12 Mice (C57BL/6) underwent an IR (ischemia reperfusion) protocol corresponding to 40 minutes of left coronary artery occlusion followed by 60 minutes of reperfusion. An other group of 12 mice underwent a postC protocol comprising, after the 40 minutes of ischemia, 3 cycles of 1-minute reperfusion and 1-minute reocclusion preceding the 60 minutes of reperfusion. In addition, 5 other groups were subjected to a PostC protocol applied at various times after the onset of reperfusion. In the group named PostC dt5 (n=6), the three cycles of PostC algorithm were applied 5 min after the onset of reperfusion; for the PostC dt10 (n=6), PostC dt15 (n=6), PostC dt30 (n=6) and PostC dt45 (n=6) groups, the 3 cycles were applied respectively 10, 15, 30 and 45 min after the onset of reperfusion. A Preconditioning (PreC group: n=7) was performed applying 3 cycles IR of 1 min. before the 40 min. of ischemia. Determination of area at risk (AR) and infarct size (Inf) was assessed by TTC staining and planimetry. Infarct size was significantly reduced in PreC and PostC animals compared to IR: (Inf/AR: 9±2, n=7 and 14.8 ± 2.7, n=12 respectively versus 50.1 ± 2.1, n=14). This cardioprotection was also observed in the PostC dt5, PostC dt10, PostC dt15 and PostC dt30 groups, compared to IR wild-type animals (Inf/AR: 14.8, 20.2, 23.1, 22.1, 28.6 % versus 50.1, respectively; p<0.05). When the postconditioning protocol was delayed 45 minutes, the cardioprotective effect was lost (infarct size/area at risk: 42.2 % for postC dt 45 versus 14.8 % for postC; p<0.05). This study clearly shows that postconditioning reduces infarct size in this mouse model of ischemia-reperfusion and that the efficiency of cardioprotection is maintained even if the protocol is applied until 30 minutes after the onset of reperfusion.