title: Hypercholesterolemia abrogates an increased resistance of diabetic rat hearts to ischemia-reperfusion injury.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, 832 32, Bratislava, Slovak Republic. adameova@fpharm.uniba.sk
authors.forename: A
authors.initials: A
authors.lastname: Adameová
authors.forename: M
authors.initials: M
authors.lastname: Kuzelová
authors.forename: E
authors.initials: E
authors.lastname: Andelová
authors.forename: V
authors.initials: V
authors.lastname: Faberová
authors.forename: D
authors.initials: D
authors.lastname: Pancza
authors.forename: P
authors.initials: P
authors.lastname: Svec
authors.forename: A
authors.initials: A
authors.lastname: Ziegelhöffer
authors.forename: T
authors.initials: T
authors.lastname: Ravingerová
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000139:chemically induced / Q000150:complications*; D013311:Streptozocin; D017180:Tachycardia, Ventricular / Q000473:pathology
chemical_list: D001786:Blood Glucose; D013311:Streptozocin; D002784:Cholesterol