Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat.
Author(s): Garjani A, Andalib S, Biabani S, Soraya H, Doustar Y, Garjani A, Maleki-Dizaji N
Affiliation(s): Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Publication date & source: 2011-09, Eur J Pharmacol., 666(1-3):135-41. Epub 2011 May 9.
Publication type: Research Support, Non-U.S. Gov't
The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 +/- 94 to +1588 +/- 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 +/- 190 to -2939 +/- 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 +/- 1 and 4 +/- 1.4 versus 8 +/- 3.5 and 14 +/- 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration. Copyright (c) 2011 Elsevier B.V. All rights reserved.