Assessment of the prophylactic role of aspirin and/or clopidogrel on experimentally induced acute myocardial infarction in hypercholesterolemic rats

Abstract

Introduction: Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI).

Aim: The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats.

Methods: Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-β1 (TGF-β1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats.

Results: Isoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-β1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately.

Conclusion: Combination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI.

Fig. 1

Isoproterenol induced myocardial infarction

Fig. 2

Box plots for comparison of mean values of serum pentraxin3 (PTX3) (pg/ml) in the studied groups

Fig. 3

Box plots for comparison of mean values of serum transforming growth factor-beta1 (TGF-β) (ng/ml) in the studied groups

Fig. 4

Box plots for Comparison of mean values of serum creatine kinase (CK) (U/L) in the studied groups

Fig. 5

Box plots for comparison of mean values of serum lactate dehydrogenase (LDH) (U/L) in the studied groups