Pretreatment with antiplatelet drugs improves the cardiac function after myocardial infarction without reperfusion in a mouse model
Abstract
Background: Reperfusion therapy is known to improve prognosis and limit myocardial damage after
myocardial infarction (MI). The administration of antiplatelet drugs prior to percutaneous coronary
intervention also proves beneficial to patients with acute MI (AMI). However, a good number of AMI
patients do not receive reperfusion therapy, and it is not clear if they would benefit from antiplatelet
pre-treatment.
Methods: Experimental C57BL/6 mice were randomly allocated to five groups: the sham group,
control, post-treatment, pre-treatment, and pre- and post-treatment groups. Acetylsalicylic acid (15 mg/kg), clopidogrel (11 mg/kg), ticagrelor (27 mg/kg), and prasugrel (1.5 mg/kg) were intragastrically administered in the treatment groups. On day 7 post MI, cardiac function and cardiac fibrosis were evaluated using echocardiography and Masson’s trichrome staining, respectively. Histopathological examinations were performed on tissue sections to grade inflammatory cell infiltration. Platelet inhibition was monitored by measuring thrombin-induced platelet aggregation.
Results: Left ventricular ejection fraction and fractional shortening improved significantly (p < 0.01)
in the pre-treatment groups when compared to the post-treatment and control groups. A significant
(p < 0.01) decrease in cardiac fibrosis was observed in the pre-treatment group, compared with the posttreatment and control groups. Inflammatory cell infiltration significantly decreased in the pre-treatment group compared with the control group (p < 0.05). Thrombin-induced platelet aggregation was significantly inhibited by antiplatelet drugs, but increased with the exposure to H2O2.
Conclusions: In the absence of reperfusion therapy, pre-treatment with antiplatelet drugs successfully
improved cardiac function, reduced cardiac fibrosis and inflammatory cell infiltration, and inhibited oxidative stress-induced platelet aggregation after MI in the mouse model.
Keywords: antiplatelet drugspre-treatmentmyocardial infarctioncardiac functionreperfusion therapy
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