Document Detail

Stimulation of endogenous prostacyclin protects the reperfused pig myocardium from ischemic injury.
MedLine Citation:
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
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    
Other Details:
Languages:  eng     Pagination:  397-405     Citation Subset:  IM    
Institut für Pharmakologie, Heinrich-Heine Universität Düsseldorf, FRG.
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MeSH Terms
6-Ketoprostaglandin F1 alpha / blood
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*
Stimulation, Chemical
Swine, Miniature
Thromboxane A2 / blood
Ventricular Function, Left / drug effects,  physiology
Reg. No./Substance:
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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