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We tested the hypothesis that daunorubicin (DAU) cardiotoxicity alters expression of cytokines involved in stem cell migration and homing. Male Wistar rats were treated with daunorubicin to induce acute DAU cardiomyopathy (6 × 3 mg/kg, i.p., every 48 hr, DAU-A) or subchronic DAU cardiomyopathy (15 mg/kg, i.v., DAU-C). The left ventricle was catheterized. The animals were killed 48 hr (DAU-A) and 8 weeks (DAU-C) after the last dose of DAU. Expression of foetal genes (Nppa, Nppb), isomyosins (Myh6, Myh7), sources of oxidative stress (Abcb8, gp91phox), cytokines (Sdf-1, Cxcr4, Scf, Vegf, Hgf, Igf-1), markers of cardiac progenitor (c-kit, Atnx-1), endothelial progenitor (CD34, CD133) and mesenchymal (CD44, CD105) stem cells were determined by qRT-PCR in left ventricular tissue. Reduced body-weight, decreased left ventricular weight and function, and elevated Nppa, Nppb, Myh7 were observed in both models. Myh6 decreased only in DAU-C, which had a 35% mortality. Up-regulated gp91phox and down-regulated Abcb8 in DAU were present only in DAU-C where we observed markedly decreased expressions of Scf and Vegf as well as expressions of stem cell markers. Down-regulation of cytokines and stem cell markers may reflect impaired chemotaxis, migration and homing of stem cells and tissue repair in the heart in subchronic but not acute model of DAU cardiomyopathy., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Abstract: Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark – Pycnogenol® (PYC) with hypoglycaemic and antioxidant properties in 8–9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p <0.05) and significantly increased mean arterial blood pressure (by 19%; p <0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p <0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p <0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p <0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy. [Copyright &y& Elsevier]