Cerivastatin and hypercholesterolemia reduce apoptosis of cardiomyocytes in guinea pig papillary muscle subjected to hypoxia/reoxygenation.
The aim of this study was to assess how cerivastatin influences contractility and degree of myocardial damage in papillary muscle subjected to hypoxia-reoxygenation in hypercholesterolemic guinea pigs. Study group consisted of guinea pigs, fed standard, hypercholesterolemic or hypercholesterolemic diets with low dose of cerivastatin. During experimental hypoxia-reoxygenation, the contractility was measured. Apoptosis of cardiomioctes was assessed with the use of TUNEL technique. Total cholesterol in standard, hypercholesterolemic and cerivastatin-treated group was 35 +/- 8 mg/dl, 131.6 +/- 30.4 mg/dl and 121.2 +/- 26.2 mg/dl, respectively, and was significantly higher in rats fed hypercholesterolemic and hypercholesterolemic + cerivastatin diets than in control group (p < 0.01). There were no significant differences between all analyzed groups in the post-ischemic cardiac function. Percentage of apoptotic cells after hypoxia-reoxygenation injury in groups fed standard, hypercholesterolemic and hypercholesterolemic + cerivastatin diets was 30 +/- 8%, 20 +/- 4% and 5 +/- 7%, respectively, and was significantly lower in groups that received hypercholesterolmic (p < 0.01) and hypercholesterolemic + cerivastatin (p < 0.001) diets in comparison with standard diet-fed group. In the group treated with cerivastatin, the percentage of apoptotic cells was additionally lower in comparison with hypercholesterolemic group (p < 0.01). Negative correlation between percentage of apoptotic cells and HDL level was found when all groups were considered jointly (r = -0.41, p < 0.05). Our study clearly shows that cerivastatin in hypercholesterolemic animals and hypercholesterolemia itself limit cardiomiocyte damage after hypoxia-reoxygenation.
Dworakowski
Rafał
R
Department of Cardiology, Medical University of Gdańsk, Debinki 7, PL 80-211 Gdańsk, Poland.
Dworakowska
Dorota
D
Kocic
Ivan
I
Wirth
Tomas
T
Gruchała
Marcin
M
Kamiński
Maciej
M
Petrusewicz
Jacek
J
Yla-Herttuala
Seppo
S
Rynkiewicz
Andrzej
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D006168:Guinea Pigs; D006937:Hypercholesterolemia / Q000473:pathology*; D000860:Hypoxia / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*
D002791:Cholesterol, Dietary; D011725:Pyridines; C086276:cerivastatin