Hypercholesterolemia abrogates an increased resistance of diabetic rat hearts to ischemia-reperfusion injury

被引:17
作者
Adameova, A. [1 ]
Kuzelova, M.
Andelova, E.
Faberova, V.
Pancza, D.
Svec, P.
Ziegelhoffer, A.
Ravingerova, T.
机构
[1] Comenius Univ, Fac Pharm, Dept Pharmacol & Toxicol, Bratislava 83232, Slovakia
[2] Slovak Acad Sci, Heart Res Inst, Bratislava, Slovakia
[3] VULM AS, Dept Expt Pharmacol, Modra, Slovakia
关键词
arrhythmias; experimental diabetes; hypercholesterolemia; infarction; myocardial ischemia-reperfusion injury;
D O I
10.1007/s11010-006-9282-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Both, diabetes mellitus (DM) and hypercholesterolemia (HCH) are known as risk factors of ischemic heart disease, however, the effects of experimental DM, as well as of HCH alone, on ischemia/reperfusion-induced myocardial injury are not unequivocal. We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in rat hearts in the acute phase of DM. Our objectives were thus to extend our knowledge on how DM in combination with HCH, a model that is relevant to diabetic patients with altered lipid metabolism, may affect the size of myocardial infarction and susceptibility to arrhythmias. A combination of streptozotocin (STZ; 80 mg/kg, i.p.) and the fat-cholesterol diet (1% cholesterol, 1% coconut oil; FCHD) was used as a double-disease model mimicking DM and HCH simultaneosly occurring in humans. Following 5 days after STZ injection and FCHD leading to increased blood glucose and cholesterol levels, anesthetized open-chest diabetic, diabetic-hypercholesterolemic (DM-HCH) and age-matched control rats were subjected to 6-min ischemia (occlusion of LAD coronary artery) followed by 10 reperfusion to test susceptibility to ventricular arrhythmias in the in vivo experiments and to 30-min ischemia and subsequent 2-h reperfusion for the evaluation of the infarct size (IS) in the Langendorff-perfused hearts. The incidence of the most life-threatening ventricular arrhythmia, ventricular fibrillation, was significantly increased in the DM-HCH rats as compared with non-diabetic control animals (100% vs. 50%; p < 0.05). Likewise, arrhythmia severity score (AS) was significantly higher in the DM-HCH rats than in the controls (4.9 +/- 0.2 vs. 3.5 +/- 0.5; p < 0.05), but was not increased in the diabetic animals (AS 3.7 +/- 0.9; p > 0.05 vs. controls). Diabetic hearts exhibited a reduced IS (15.1 +/- 3.0% of the area at risk vs. 37.6 +/- 2.8% in the control hearts; p < 0.05), however, a combination of DM and HCH increased the size of myocardial infarction to that observed in the controls. In conclusion, HCH abrogates enhanced resistance to ischemia-reperfusion injury in the diabetic rat heart.
引用
收藏
页码:129 / 136
页数:8
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