A Cholesterol-Rich Diet Improves Resistance to Ischemic Insult in Mouse Hearts but Suppresses the Beneficial Effect of Post-Conditioning

作者:Lauzier Benjamin*; Delemasure Stephanie; Pesant Matthieu; Collin Bertrand; Duvillard Laurence; Vergely Catherine; Connat Jean Louis; Rochette Luc
来源:Journal of Heart and Lung Transplantation, 2009, 28(8): 821-826.
DOI:10.1016/j.healun.2009.04.030

摘要

Background: Conflicting evidence is reported about the beneficial effects of post-conditioning (Post-C) in pathologic conditions. A pathologic mouse model of hypercholesterolemia was used. The study examined the effect of Post-Con cardiac recovery after the ischemia-reperfusion sequence and the effect of Post-Con on low-density lipoprotein receptor-deficient (LDLR(-/-)) mice and control animals. Methods: LDLR(-/-) and C57b1/6 mice were fed for 8 weeks with a high-cholesterol (1.25%) or normal diet. The hearts were isolated and perfused on a working heart apparatus. The hearts underwent 20 minutes of global total ischemia, followed by 36 minutes of reperfusion. Post-Con was applied at the onset of reperfusion with three 10-second cycles of ischemia-reperfusion. Tissue injury Was evaluated (triphenyltetrazolium chloride staining), and superoxide anion production was assessed (dihydroethidium). Results: Post-ischemia recovery was very low in the control and LDLR(-/-) groups, and Post-C induced increase in functional recovery (p < 0.05). The high-cholesterol groups showed better cardiac recovery, but Post-C did not accentuate this improvement. Post-C was associated with a significant reduction in tissue injury and superoxide production in LDLR(-/-) and C57b1/6 (P < 0.05), but these effects were not observed in animals fed the high-cholesterol diet. Conclusions: Our results demonstrated that control and LDLR(-/-) mice may be protected by Post-C, and an 8-week high-cholesterol diet led to improved recover), of the myocardium after the ischemia-reperfusion sequence in both series. However, the endogenous protective mechanism of Post-C appears to be lost in the presence of hypercholesterolemia. J Heart Lung Transplant 2009;28:821-6.

  • 出版日期2009-8