title: Diabetic cardiomyopathy in rats: alleviation of myocardial dysfunction caused by Ca2+ overload.
abstract: There is some evidence that diabetic hearts are more resistant to ischaemia/reperfusion injury due to alterations in Ca2+ handling. Our objective was to explore this hypothesis in the model of Ca2+ overloaded heart (calcium paradox, CaP). Diabetes was induced by streptozotocin (45 mg/kg, i.v.). Despite regular insulin treatment blood glucose was increased. After a diabetes duration of 9 weeks the heart/body weight ratio was higher than in age-matched controls, and the heart rate, the coronary flow (CF) and the rate of contraction and relaxation was reduced as assessed in Langendorff preparation. Depressed function was accompanied by a lower content of high energy phosphates and ultrastructural alterations, such as an increased number of glycogen granules, lipid droplets and changes in the walls of capillaries leading to the narrowing of their lumen. In controls, readmission of Ca2+ into Ca(2+)-depleted hearts resulted in extensive deterioration of heart function, development of contraction bands, ultrastructural damage and loss of ATP. Diabetic hearts, despite impaired performance before CaP, showed an improved recovery of heart function manifested by restoration of electrical and contractile activity, as well as CF after Ca2+ repletion. This corresponded to better maintenance of energy metabolism and preservation of ultrastructure. In conclusion, diabetic hearts exhibit greater resistance to Ca2+ overload. Depressed heart function may account for this protective effect: bradycardia facilitates saving ATP; lower CF results in a slower rate of Ca2+ washout from the heart during Ca2+ depletion thus causing less damage to the cell membrane and maintenance of its integrity.
authors.affiliation: Institute for Heart Research, Slavak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: T
authors.initials: T
authors.lastname: Ravingerová
authors.forename: J
authors.initials: J
authors.lastname: Styk
authors.forename: D
authors.initials: D
authors.lastname: Pancza
authors.forename: N
authors.initials: N
authors.lastname: Tribulová
authors.forename: J
authors.initials: J
authors.lastname: Seboková
authors.forename: K
authors.initials: K
authors.lastname: Volkovová
authors.forename: A
authors.initials: A
authors.lastname: Ziegelhoffer
authors.forename: J
authors.initials: J
authors.lastname: Slezák
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009202:Cardiomyopathies / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000227:Adenine Nucleotides; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D002118:Calcium