Beneficial Effects of Myocardial Postconditioning are Associated With Reduced Oxidative Stress in a Senescent Mouse Model

Abstract : Background. There is at present a tragic lack of organs available for transplantation. This has led to the harvesting of hearts from older donors. Unfortunately, hearts from such donors are much more sensitive to ischemic insult. Models such as "Senescence Accelerated Mouse" Prone 8 (SAM-P8) can help understand this sensitivity. New cardioprotective techniques such as postconditioning (PostC) could be of interest in this context. We studied (1) senescence in vessels and hearts and (2) the ability of the senescent heart to adapt to an ischemia-reperfusion (I/R) sequence in the context of PostC. Methods. Isolated working mouse hearts (8 months) were subjected to total ischemia, followed by 36 min of reperfusion; PostC was performed in the first minutes of reperfusion as three 10-sec sequences of I/R. Superoxide anion (O 2 ⅐Ϫ) production was evaluated on heart and aorta cryosections with the dihydroethidium staining method. The collagen content in aortas was quantified. Results. The aortas of SAM-P8 mice showed a higher production of O 2 ⅐Ϫ and a higher collagen content than did those of SAM-R1 mice (PϽ0.05). During reperfusion, SAM-P8 hearts showed the worst recovery of cardiac output. PostC significantly reduced reperfusion dysfunction (PϽ0.05) and was associated with a reduction in heart O 2 ⅐Ϫ staining. Conclusions. These results indicate that SAM-P8 presents a high degree of cardiovascular oxidative stress and a higher susceptibility to I/R injury, which confirms the senescence of the cardiovascular system in these animals. However, they remain sensitive to cardioprotection afforded by in vitro PostC.