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 C57bl/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 (triphenyl-tetrazolium 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 an 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 C57bl/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 recovery 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.