A cholesterol-rich diet improves resistance to ischemic insult in mouse hearts but suppresses the beneficial effect of post-conditioning.
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.
Lauzier
Benjamin
B
Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaire Expérimentale, Faculté de Médecine et Pharmacie, Dijon, France. benjaminlauzier@yahoo.fr
Delemasure
Stephanie
S
Pesant
Matthieu
M
Collin
Bertrand
B
Duvillard
Laurence
L
Vergely
Catherine
C
Connat
Jean-Louis
JL
Rochette
Luc
L
D000222:Adaptation, Physiological; D000818:Animals; D002784:Cholesterol / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006937:Hypercholesterolemia / Q000503:physiopathology*; D051379:Mice; D017202:Myocardial Ischemia / Q000178:diet therapy* / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D020127:Recovery of Function
D004041:Dietary Fats; D002784:Cholesterol