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Two Classes of Anti-Platelet Drugs Reduce Anatomical Infarct Size in Monkey Hearts

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Abstract

Background

Recent studies in rabbits have demonstrated that platelet P2Y12 receptor antagonists are cardioprotective, and that the mechanism is surprisingly not related to blockade of platelet aggregation but rather to triggering of the same signal transduction pathway seen in pre- and postconditioning. We wanted to determine whether this same cardioprotection could be documented in a primate model and whether the protection was limited to P2Y12 receptor antagonists or was a class effect.

Methods

Thirty-one macaque monkeys underwent 90-min LAD occlusion/4-h reperfusion.

Results

The platelet P2Y12 receptor blocker cangrelor started just prior to reperfusion significantly decreased infarction by an amount equivalent to that seen with ischemic postconditioning (p < 0.001). For any size of risk zone, infarct size in treated hearts was significantly smaller than that in control hearts. OM2, an investigational murine antibody against the primate collagen receptor glycoprotein (GP) VI, produced similar protection (p < 0.01) suggesting a class effect. Both cangrelor and OM2 were quite effective at blocking platelet aggregation (94 % and 97 %, respectively).

Conclusions

Thus in a primate model in which infarct size could be determined directly platelet anti-aggregatory agents are cardioprotective. The important implication of these investigations is that patients with acute myocardial infarction who are treated with platelet anti-aggregatory agents prior to revascularization may already be in a postconditioned state. This hypothesis may explain why in recent clinical trials postconditioning-mimetic interventions which were so protective in animal models had at best only a modest effect.

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Acknowledgments

This study was supported in part by grant HL-20648 from the Heart, Lung and Blood Institute of the National Institutes of Health and by funds supplied by Otsuka Maryland Medicinal Labs., Inc., Rockville, MD. Cangrelor was synthesized by a private firm.

Disclosures

Monkey studies were funded by a contract with Otsuka Maryland Medicinal Labs, Rockville, MD.

Author information

Authors and Affiliations

  1. Department of Physiology, MSB 3050, University of South Alabama College of Medicine, Mobile, AL, 36688, USA

    Xi-Ming Yang, Yanping Liu, Lin Cui, Xiulan Yang, James M. Downey & Michael V. Cohen

  2. Otsuka Maryland Medicinal Labs, Inc., Rockville, MD, USA

    Yongge Liu, Narendra Tandon & Junichi Kambayashi

  3. Department of Medicine, University of South Alabama College of Medicine, Mobile, AL, USA

    Michael V. Cohen

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  1. Xi-Ming Yang
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Correspondence to Michael V. Cohen.

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Yang, XM., Liu, Y., Cui, L. et al. Two Classes of Anti-Platelet Drugs Reduce Anatomical Infarct Size in Monkey Hearts. Cardiovasc Drugs Ther 27, 109–115 (2013). https://doi.org/10.1007/s10557-012-6436-7

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  • DOI: https://doi.org/10.1007/s10557-012-6436-7

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