Myocardial infarction (MI) refers to the loss of cardiomyocytes due to inadequate coronary blood flow and subsequently a reduced
oxygen supply. Activation of
N-methyl-D-aspartate (
NMDA) receptors has been linked to
myocardial infarction. The aim of the present study was to determine the cardioprotective effects of
memantine, in
myocardial infarction both in ex vivo and in vivo models. Effects of
memantine on the electrocardiogram (ECG) pattern, cardiodynamic parameters,
infarct size and lipid peroxidation were evaluated in the isolated perfused rat heart. Moreover, in in vivo studies in rats, the protective effects of
memantine on
isoproterenol-induced
myocardial infarction model (administration of 100 mg/kg
isoproterenol subcutaneously for 2 consecutive days) was evaluated by measuring ECG pattern, mean arterial pressure,
malondialdehyde (MDA) levels,
myeloperoxidase (MPO) activity,
cardiac tumor necrosis factor-alpha (TNF-α) level and cardiac remodeling. The results from the ex vivo isolated perfused heart showed that
memantine treatment increased heart rate, left ventricular systolic pressure and left ventricular maximal rate of pressure increase, and decreased
cardiac arrhythmia, MDA level and
infarct size in comparison to
ischemia/reperfusion (IR) group. The
isoproterenol-induced MI (Iso) as used in the in vivo model demonstrated that MDA levels and MPO activity were decreased in
memantine groups.
Memantine treatment reduced the expression of cardiac TNF-α in comparison to Iso group. Cardiac
fibrosis and
hypertrophy were lower in
memantine groups. In conclusion,
memantine exerts cardioprotective effects in models of
myocardial infarction, which may be attributed to reduction of pro-inflammatory and oxidative stress factors and subsequently a decrease in cardiac remodeling.