|Stimulation of endogenous prostacyclin protects the reperfused pig myocardium from ischemic injury.|
|PMID: 8423539 Owner: NLM Status: MEDLINE|
|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)|
|T Hohlfeld; H Strobach; K Schrör|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: The Journal of pharmacology and experimental therapeutics Volume: 264 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1993 Jan|
|Created Date: 1993-02-23 Completed Date: 1993-02-23 Revised Date: 2013-06-03|
Medline Journal Info:
|Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES|
|Languages: eng Pagination: 397-405 Citation Subset: IM|
|Institut für Pharmakologie, Heinrich-Heine Universität Düsseldorf, FRG.|
|APA/MLA Format Download EndNote Download BibTex|
6-Ketoprostaglandin F1 alpha
Blood Platelets / drug effects, physiology
Cyclooxygenase Inhibitors / pharmacology
Disease Models, Animal
Epoprostenol / biosynthesis, blood
Granulocytes / drug effects
Indomethacin / pharmacology
Leukocyte Count / drug effects
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*
Thromboxane A2 / blood
Ventricular Function, Left / drug effects, physiology
|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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