Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat

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 (5 mg/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/dtmax) and relaxation (LVdP/dtmin), 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 (5 mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P < 0.01). On the contrary, a high dose of atorvastatin (20 mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dtmax from + 2780 ± 94 to + 1588 ± 248 (mm Hg/s; P < 0.01) and LVdP/dtmin from − 2007 ± 190 to − 2939 ± 291 (mm Hg/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 mm Hg, 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.