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

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Lauzier, Benjamin | Delemasure, Stéphane | Debin, Régine | Sicard, Pierre | Acar, Niyazi | Brétillon, Lionel | Vergely, Catherine | Rochette, Luc

Edité par CCSD ; Oxford University Press (OUP) -

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.

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