Document Detail


Two classes of anti-platelet drugs reduce anatomical infarct size in monkey hearts.
MedLine Citation:
PMID:  23318690     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Xi-Ming Yang; Yanping Liu; Lin Cui; Xiulan Yang; Yongge Liu; Narendra Tandon; Junichi Kambayashi; James M Downey; Michael V Cohen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  27     ISSN:  1573-7241     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-19     Completed Date:  2013-08-30     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  109-15     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Monophosphate / administration & dosage,  analogs & derivatives*
Animals
Antibodies / administration & dosage*
Blood Pressure / drug effects
Heart Rate / drug effects
Macaca fascicularis
Male
Myocardial Infarction / drug therapy*,  physiopathology
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / administration & dosage*
Platelet Membrane Glycoproteins / immunology*
Purinergic P2Y Receptor Antagonists / administration & dosage*
Grant Support
ID/Acronym/Agency:
HL-20648/HL/NHLBI NIH HHS; R01 HL020648/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Platelet Aggregation Inhibitors; 0/Platelet Membrane Glycoproteins; 0/Purinergic P2Y Receptor Antagonists; 0/platelet membrane glycoprotein VI; 415SHH325A/Adenosine Monophosphate; 6AQ1Y404U7/cangrelor
Comments/Corrections
Comment In:
Cardiovasc Drugs Ther. 2013 Apr;27(2):105-7   [PMID:  23354515 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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