Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats

• Published in: Pharmacological reports Vol. 64; no. 6; pp. 1476 - 1484
• Main Authors: Soraya, Hamid, Khorrami, Arash, Garjani, Afagh, Maleki-Dizaji, Nasrin, Garjani, Alireza
• Format: Journal Article
• Language: English
• Published: Cham Elsevier Urban & Partner Sp. z o.o 2012; Springer International Publishing
• Subjects: Administration, Oral; Animals; Arterial Pressure - drug effects; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Safety and Pharmacovigilance; Edema, Cardiac - pathology; Edema, Cardiac - physiopathology; Edema, Cardiac - prevention & control; Electrocardiography; Heart Rate - drug effects; Isoproterenol; Male; Metformin - administration & dosage; Metformin - pharmacology; metfromin; Myocardial Contraction - drug effects; myocardial infarction; Myocardial Infarction - chemically induced; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardium - pathology; Necrosis; Pharmacotherapy; Pharmacy; Rats; Rats, Wistar; Stroke Volume - drug effects; Time Factors; Ventricular Function, Left - drug effects; Ventricular Pressure - drug effects; isoproterenol; metfromin; myocardial infarction; electrocardiography
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(12)70945-3

It has been proposed that metformin exerts protective effects on ischemic hearts. In the present study, we evaluated the effects of metformin on cardiac function, hemodynamic parameters, and histopathological changes in isoproterenol-induced myocardial infarction (MI). Male Wistar rats were divided into six groups (n=6) of control, isoproterenol (100mg/kg; MI), metformin alone (100mg/kg; sham), and metformin (25, 50, 100mg/kg) with isoproterenol. Subsequently, isoproterenol was injected subcutaneously for two consecutive days and metformin was administered orally twice daily for the same period. Isoproterenol elevated ST-segment and suppressed R-amplitude on ECG. All doses of metformin were found to significantly amend the ECG pattern. Isoproterenol also caused an intensive myocardial necrosis along with a profound decrease in arterial pressure indices, left ventricular contractility (LVdP/dtmax) and relaxation (LVdP/dtmin), and an increase in left ventricular enddiastolic pressure (LVEDP). Histopathological analysis showed a marked attenuation of myocyte necrosis in all metformin treated groups (p<0.001). Metformin at 50mg/kg strongly (p<0.01) increased LVdP/dtmax from 2988±439 (mmHg/s) in the MI group to 4699±332 (mmHg/s). Similarly, treatment with 50mg/kg of metfromin lowered the elevated LVEDP from 27±8mmHg in the myocardial infarcted rats to a normal value of 5±1.4 (mmHg; p<0.01) and the heart to body weight ratio as an index of myocardial edematous from 4.14±0.13 to 3.75±0.08 (p<0.05). The results of this study demonstrated that a short-term administration of metformin strongly protected the myocardium against isoproterenol-induced infarction, and thereby suggest that patients suffering from myocardial ischemia could benefit from treatment with metformin.