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RESEARCH PRODUCT

In senescence accelerated mouse (SAM) heart, the protective effect of postconditioning is associated with a decrease in oxidative stress

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Supplément vol.27, World Congress of Cardiology 2006; International audience; The senescent heart susceptibility to ischemia (I) triggers multiple processes especially oxidative stress but precise mechanisms remain unclear. New animal’s models such as "Senescence Accelerated Mouse" Prone 8 (SAM-P8) and their control (SAM-R1) can be useful for a better understanding of aging process. We studied heart adaptation of these mice to I/reperfusion (R) sequence and a putative cardioprotector effect of post-conditioning (PC). Isolated working mice (8 months) hearts were subjected to a global total ischemia (20 minutes at 38°C), followed by 40 minutes of reperfusion. 4 groups of hearts were constituted: 1) SAM-R1 (n=8), 2) SAM-P8 (n=9), brief ischemia applied during the onset of reperfusion 3 times I: 10 sec, R: 10 sec for PC groups, 3) SAM-R1 PC (n=7) and 4) SAM-P8 PC (n=8). Myocardial functions (left ventricular end systolic/diastolic pressures, contractility, relaxation, aortic flow, coronary flow and heart rate) were recorded throughout the protocol. Hearts were then frozen and superoxide anion (O•− 2 ) production has been evaluated on cryosections using a fluorescent probe Dihydroethidium (DHE). During pre-I period, cardiac functional parameters were comparable in all groups. SAM-P8 heart showed the worst reperfusion parameters compare to SAM-R1; for instance cardiac output (0.60±0.33 ml/min vs. 1.84±0.64 ml/min, p<0.05). PC induced a significant better functional recovery on both group (3.96±0.68 ml/min SAM-R1 PC vs. 3.20±0.78 ml/min SAM-P8 PC; p<0.05). Furthermore PC is associated with a significant reduction of superoxide production on heart slice has been observed (p<0.05). These results indicate that SAM-P8 mice, a murine model of aging, present a susceptibility to reversible I and are still sensitive to PC. This cardioprotection is associated with a decrease of free radicals production. These results demonstrate a role of the oxidative stress in the process of myocardial adaptation to I/R sequences.