Evidence map›Paper›PMID 23233653›Full record

ArticleJournal of cardiovascular pharmacology and therapeutics2013

Platelet P2Y₁₂ blockers confer direct postconditioning-like protection in reperfused rabbit hearts.

Xi-Ming Yang, Yanping Liu, Lin Cui, Xiulan Yang, Yongge Liu, Narendra Tandon, Junichi Kambayashi, James M Downey, Michael V Cohen

Open access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cardiovascular pharmacology and therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 144 citations in OpenAlex.

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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Xi-Ming YangDepartment of Physiology, University of South Alabama College of Medicine, Mobile, AL, USA.
Yanping Liu
Lin Cui
Xiulan Yang
Yongge Liu
Narendra Tandon
Junichi Kambayashi
James M Downey
Michael V Cohen
University of South Alabama · USOtsuka (United States) · US

Funding

PHYSICAL FACTORS AND CORONARY FLOWR01HL020648 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI DOWNEY, JAMES M · 1985 to 2011
$2.7M
NHLBI NIH HHS HL-20648NHLBI NIH HHS R01 HL020648
6 · The paper itself

Abstract

backgroundBlockade of platelet activation during primary percutaneous intervention for acute myocardial infarction is standard care to minimize stent thrombosis. To determine whether antiplatelet agents offer any direct cardioprotective effect, we tested whether they could modify infarction in a rabbit model of ischemia/reperfusion caused by reversible ligation of a coronary artery. METHODS AND

resultsThe P2Y₁₂ (adenosine diphosphate) receptor blocker cangrelor administered shortly before reperfusion in rabbits undergoing 30-minute regional ischemia/3-hour reperfusion reduced infarction from 38% of ischemic zone in control hearts to only 19%. Protection was dose dependent and correlated with the degree of inhibition of platelet aggregation. Protection was comparable to that seen with ischemic postconditioning (IPOC). Cangrelor protection, but not its inhibition of platelet aggregation, was abolished by the same signaling inhibitors that block protection from IPOC suggesting protection resulted from protective signaling rather than anticoagulation. As with IPOC, protection was lost when cangrelor administration was delayed until 10 minutes after reperfusion and no added protection was seen when cangrelor and IPOC were combined. These findings suggest both IPOC and cangrelor may protect by the same mechanism. No protection was seen when cangrelor was used in crystalloid-perfused isolated hearts indicating some component in whole blood is required for protection. Clopidogrel had a very slow onset of action requiring 2 days of treatment before platelets were inhibited, and only then the hearts were protected. Signaling inhibitors given just prior to reperfusion blocked clopidogrel's protection. Neither aspirin nor heparin was protective.

conclusionsClopidogrel and cangrelor protected rabbit hearts against infarction. The mechanism appears to involve signal transduction during reperfusion rather than inhibition of intravascular coagulation. We hypothesize that both drugs protect by activating IPOC's protective signaling to prevent reperfusion injury. If true, patients receiving P2Y₁₂ inhibitors before percutaneous intervention may already be postconditioned thus explaining failure of recent clinical trials of postconditioning drugs.

Indexed as

Adenosine MonophosphateAnimalsCardiotonic AgentsClopidogrelCoronary VesselsFemaleHeartIn Vitro TechniquesIschemic PostconditioningMaleMyocardial InfarctionMyocardial Reperfusion InjuryMyocardiumPerfusionPlatelet ActivationPlatelet Aggregation InhibitorsAdenosine MonophosphatecangrelorCardiotonic AgentsClopidogrelPlatelet Aggregation InhibitorsProtein Kinase InhibitorsPurinergic P2Y Receptor AntagonistsReceptors, Purinergic P2Y12Ticlopidine

Identifiers

PMID23233653
PMCPMC3625463
OpenAlexW2165248515

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.