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

• Published in: European journal of pharmacology Vol. 666; no. 1; pp. 135 - 141
• Main Authors: Garjani, Alireza, Andalib, Sina, Biabani, Sajjad, Soraya, Hamid, Doustar, Yousef, Garjani, Afagh, Maleki-Dizaji, Nasrin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2011; Elsevier
• Subjects: Animals; Atorvastatin; Atorvastatin Calcium; Biological and medical sciences; Body Weight - drug effects; Cardiology. Vascular system; Coenzyme Q10; Drug Interactions; Heart; Heart failure; Heart Failure - chemically induced; Heart Failure - drug therapy; Heart Failure - pathology; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hemodynamics - drug effects; Heptanoic Acids - administration & dosage; Heptanoic Acids - pharmacology; Heptanoic Acids - therapeutic use; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Isoproterenol; Isoproterenol - pharmacology; Male; Medical sciences; Myocardium - pathology; Organ Size - drug effects; Pharmacology. Drug treatments; Pyrroles - administration & dosage; Pyrroles - pharmacology; Pyrroles - therapeutic use; Rats; Rats, Wistar; Ubiquinone - administration & dosage; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology; Ubiquinone - therapeutic use; Ventricular Dysfunction, Left - drug therapy; Heart failure; Atorvastatin; Isoproterenol; Coenzyme Q10; Agonist; Isoprenaline; Rat; Cardiovascular disease; β2-Adrenergic receptor; β-Adrenergic receptor agonist; Hypocholesterolemic agent; β-Adrenergic receptor; Ubiquinone; Heart disease; HMG-CoA reductase inhibitor; Enzyme; Bronchodilator; Rodentia; Enzyme inhibitor; Statin derivative; Antioxidant; Vertebrata; Mammalia; Animal; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent
• DOI: 10.1016/j.ejphar.2011.04.061
• ISSN: 0014-2999

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/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 (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 LV dP/ dt max from + 2780 ± 94 to + 1588 ± 248 (mm Hg/s; P < 0.01) and LV dP/ dt min 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.