Cardioprotective properties of the platelet P2Y12 receptor inhibitor prasugrel on cardiac ischemia/reperfusion injury



The effects of prasugrel, a third-generation thienopyridine, on myocardial infarction, and ischemia-induced ventricular arrhythmias was evaluated in open-chest anesthetized rats. The role of protein kinase C and phosphoinositide 3-kinase pathways in these effects was also examined.


The effect of P2Y12 receptor inhibition by prasugrel (3–10 mg/kg, po) on infarct size after 30-min coronary artery occlusion and 120-min reperfusion or on arrhythmias after 7-min coronary occlusion and 7-min reperfusion was evaluated.


In the control group, 31.25 ± 3.01% of the risk zone infarcted. At both prasugrel doses, infarct size was significantly smaller than that in the control group: 5.03 ± 0.81% for 3 mg/kg (p < 0.0001), and 8.78 ± 2.04% for 10 mg/kg (p < 0.0001). The protein kinase C antagonist chelerythrine abolished the anti-infarct effect of prasugrel at 24.77 ± 1.73% as did the phosphoinositide 3-kinase antagonist wortmannin abolished the anti-infarct effect of prasugrel at 27.45 ± 2.74%. Ten mg/kg prasugrel reduced the duration of VT (p = 0.0152 vs control), and wortmannin, but not chelerythrine, reversed the effect of prasugrel on arrhythmias (p = 0.0295).


The selective P2Y12 inhibitor prasugrel provides effective protection against myocardial infarction and ischemia-induced ventricular arrhythmias in rats. As in ischemic postconditioning, protein kinase C and phosphoinositide 3-kinase signaling pathways play a role in this protection.

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This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) 1002 program (Grant number: 216S328).


This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) 1002 program (Grant number: 216S328).

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Correspondence to Turhan Dost.

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All applicable international, national, and/or institutional guidelines for the care and use of laboratory animals were followed and approved by the Animal Care Committee of Aydin Adnan Menderes University, Turkey. No human studies were carried out for this article.

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Dost, T. Cardioprotective properties of the platelet P2Y12 receptor inhibitor prasugrel on cardiac ischemia/reperfusion injury. Pharmacol. Rep (2020).

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  • P2Y12 receptor
  • Myocardial ischemia/reperfusion injury
  • Arrhythmia
  • PKC
  • PI3K