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Few effective porcine models of myocardial infarction (MI) related to platelet thrombus formation are available. In this study, we established a novel porcine MI model and examined the effect of dual antiplatelet therapy (DAPT) with aspirin and prasugrel, a P2Y12 antagonist, using this MI model. Thrombotic MI was photochemically induced using rose bengal. Male miniature pigs were divided into 3 treatment groups: Sham, MI, and DAPT. In the DAPT group, aspirin (10mg/kg, p.o.) and prasugrel (1mg/kg, p.o.) were administered 4h before photo-irradiation. Platelet aggregation, MI volume, and cardiac function were evaluated 24h after photo-irradiation. Inhibition of ADP-induced platelet aggregation in the DAPT group was about 45%, similar to the effects of DAPT in a clinical setting. No MI was observed in the Sham group, and MI volume was 12.9±2.9% in the left ventricle (P=0.0016) in the MI group. Additionally, an increase in end-systolic volume (P=0.0006), and a decrease in stroke volume (P=0.0001) and ejection fraction (P<0.0001) were observed in the MI group compared to the Sham group without any changes in end-diastolic volume. DAPT significantly decreased MI volume (P=0.0006) and ameliorated cardiac dysfunction compared to the MI group. In conclusion, a novel porcine model of thrombotic MI with cardiac dysfunction was established. In this model, DAPT decreased MI volume and ameliorated of cardiac dysfunction, suggesting that this porcine MI model could be useful for future research on MI and antithrombotic agents.