Abstract Body: Background: Cardioprotection in patients with acute myocardial infarction (AMI) undergoing reperfusion remains a substantial un-met medical need. Dual antiplatelet therapy (DAPT) is the standard treatment to reduce ischemic complications, yet its concomitant increase in bleeding risk challenges cardiologists. Recent studies suggest arachidonic acid (AA), an essential polyunsaturated fatty acid, may exert cardioprotection. This study aimed to evaluate the effect of oral AA on the efficacy and safety of DAPT in a porcine model of myocardial ischemia/reperfusion (MI/R) injury.
Methods: MI/R injury was induced in Bama miniature pigs (20-30 kg) via a 90-minute balloon occlusion of the left anterior descending coronary artery followed by 3 days of reperfusion. Animals were randomly assigned to standard DAPT (aspirin, loading dose 100 mg, maintenance dose 25 mg, qd + ticagrelor, loading dose 60 mg, maintenance dose 30 mg, bid) or DAPT plus oral AA (560 mg, qd). Cardiac function was evaluated by echocardiography and cardiac magnetic resonance imaging. Myocardial infarct size was quantified by triphenyltetrazolium chloride staining. Plasma cytokines were assessed by ELISA. AA metabolism was analyzed using LC-MS/MS. Gastric mucosal injury was assessed through gross morphology and histological staining.
Results: DAPT inhibited platelet aggregation, which was not affected by AA treatment. Compared to DAPT alone, the DAPT+AA group exhibited significant reduction in infarct size and myocardial edema. AA-treated pigs showed a superior recovery of left ventricular ejection fraction at 2 hours post-reperfusion compared to the DAPT group. Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were significantly decreased in the DAPT+AA group. Gross and histological evaluations revealed that AA treatment substantially attenuated DAPT-induced gastric mucosal injury and hemorrhage. This mucosal protection was accompanied by a significant elevation of the tissue levels of AA metabolites PGE₂ and PGI₂.
Conclusion: Arachidonic acid augments cardioprotection of DAPT against MI/R injury in pigs while mitigating DAPT-induced gastrointestinal mucosal injury. This study raises a promising approach by supplementing an essential nutrient for cardiac and gastrointestinal protection in AMI patients treated with DAPT.