title: Two classes of anti-platelet drugs reduce anatomical infarct size in monkey hearts.
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.
authors: Department of Physiology, MSB 3050, University of South Alabama College of Medicine, Mobile, AL 36688, USA.
authors: Xi-Ming
authors: XM
authors: Yang
authors: Yanping
authors: Y
authors: Liu
authors: Lin
authors: L
authors: Cui
authors: Xiulan
authors: X
authors: Yang
authors: Yongge
authors: Y
authors: Liu
authors: Narendra
authors: N
authors: Tandon
authors: Junichi
authors: J
authors: Kambayashi
authors: James M
authors: JM
authors: Downey
authors: Michael V
authors: MV
authors: Cohen
mesh_terms: D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*
chemical_list: D000906:Antibodies; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D058921:Purinergic P2Y Receptor Antagonists; C098341:platelet membrane glycoprotein VI; D000249:Adenosine Monophosphate; C117446:cangrelor