Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat

Acute treatment with metformin has a
cardio-protective effects by suppression of inflammatory
responses during myocardial infarction (MI) through
activation of AMP-activated protein kinase (AMPK).
Neutrophils have a pivotal role during MI-induced
inflammatory responses. Some anti-inflammatory
treatments have decreased cardiac injury and infarct
size in MI. Here we evaluated the effects of chronic pretreatment
with metformin on myocardial remodeling
and neutrophil recruitment after isoproterenol-induced
MI.
Methods: Male wistar rats were randomly assigned into
6 groups (n=6) of untreated control, sham, isoproterenol
(Iso), and pre-treated orally with 25, 50, and 100 mg/kg
of metformin, twice daily, for 14 days. Isoproterenol was injected subcutaneously (sc) at 13th and
14th days for induction of acute MI. Histopathological examinations were done on the harvested
hearts. Number of neutrophils in peripheral blood and their infiltration to myocardium were
evaluated by Gimsa staining and myeloperoxidase (MPO) assay, respectively.
Results: Histopathological analysis showed a significant attenuation of isoproterenol-induced
cardiomyocyte necrosis and fibrosis by all three doses of metformin. The heart to body
weight ratio was also decreased with all doses of metformin. Pre-treatment with metformin in
comparison to Iso (MI) group reduced peripheral neutrophils (p<0.05, p<0.01, and p<0.001 at 25,
50, and 100 mg/kg; respectively) as well as MPO activity (p<0.05 and p<0.01 at 50 and 100 mg/
kg, respectively).
Conclusion: Pre-treatment with metformin decreased post-MI myocardial injuries by reducing
cardiac remodeling and myocardial neutrophil activity. The results could be explained as a new
mechanism for cardio-protective effect of metformin