| Stimulation of endogenous prostacyclin protects the reperfused pig myocardium from ischemic injury. | |
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MedLine Citation:
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PMID: 8423539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several attempts have been undertaken to reduce the severity of ischemic myocardial injury by exogenous administration of eicosanoids and by modification of endogenous eicosanoid production. The present study investigates whether defibrotide, a compound that stimulates endogenous prostacyclin (PGI2), has a beneficial effect in experimental ischemic myocardial injury. Anesthetized, open-chest minipigs were subjected to 1 h of coronary artery occlusion, followed by 3 h of reperfusion. Defibrotide (32 mg/kg x h) or its vehicle were infused i.v. throughout the experiment. Defibrotide increased cardiac PGI2 formation 3- to 4-fold greater than control (P < .05). Thromboxane levels remained unchanged. Irreversible ischemic injury, as identified by negative tetrazolium staining, amounted to 44 +/- 6% of the area at risk in pigs receiving vehicle but was reduced to 23 +/- 4% by defibrotide (P < .05). This reduced tissue injury in defibrotide-treated pigs was associated with improved functional recovery (left ventricular pressure, + dP/dtmax), during early reperfusion. Recovery did not occur in vehicle-treated pigs. Collagen (2 micrograms/ml)-induced platelet aggregation ex vivo was increased in vehicle-treated pigs during ischemia and reperfusion, but not in animals treated with defibrotide. Polymorphonuclear neutrophil leukocyte accumulation in the ischemic border zone was reduced from 59 +/- 17 cells/mm2 in vehicle-treated pigs to 17 +/- 9 cells/mm2 by defibrotide (P < .05). Pretreatment of the animals with indomethacin (3 mg/kg) prevented the reduction of infarct size and polymorphonuclear neutrophil leukocyte infiltration by defibrotide. Indomethacin increased infarct size in vehicle- and defibrotide-treated pigs by 71 and 59%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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T Hohlfeld; H Strobach; K Schrör |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 264 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1993 Jan |
Date Detail:
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Created Date: 1993-02-23 Completed Date: 1993-02-23 Revised Date: 2013-06-03 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 397-405 Citation Subset: IM |
Affiliation:
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Institut für Pharmakologie, Heinrich-Heine Universität Düsseldorf, FRG. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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blood Animals Blood Platelets / drug effects, physiology Cyclooxygenase Inhibitors / pharmacology Disease Models, Animal Epoprostenol / biosynthesis, blood Female Granulocytes / drug effects Indomethacin / pharmacology Leukocyte Count / drug effects Male Myocardial Infarction / drug therapy, prevention & control Myocardial Ischemia / drug therapy, prevention & control Myocardial Reperfusion Injury / prevention & control* Myocardium / metabolism Neutrophils / drug effects, physiology Platelet Count / drug effects Polydeoxyribonucleotides / blood, pharmacology* Prostaglandins / physiology* Stimulation, Chemical Swine Swine, Miniature Thromboxane A2 / blood Ventricular Function, Left / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/Polydeoxyribonucleotides; 0/Prostaglandins; 35121-78-9/Epoprostenol; 438HCF2X0M/defibrotide; 53-86-1/Indomethacin; 57576-52-0/Thromboxane A2; 58962-34-8/6-Ketoprostaglandin F1 alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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