Document Detail

Protectant activity of defibrotide in cardioplegia followed by ischemia/reperfusion injury in the isolated rat heart.
MedLine Citation:
PMID:  10875586     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Previous studies have shown that defibrotide, a polydeoxyribonucleotide obtained by depolymerization of DNA from porcine tissues, has important protective effects on myocardial ischemia, which may be associated with a prostacyclin-related mechanism. The purpose of this study was to investigate the direct effects of defibrotide (given in cardioplegia or after ischemia) on a model of rat heart recovery after cardioplegia followed by ischemia/reperfusion injury.
METHODS: Isolated rat hearts, undergoing 5 minutes of warm cardioplegic arrest followed by 20 minutes of global ischemia and 30 minutes of reperfusion, were studied using the modified Langendorff model. The cardioplegia consisted of St. Thomas' Hospital solution augmented with defibrotide (50, 100, and 200 microg/mL) or without defibrotide (controls). Left ventricular mechanical function and the levels of creatine kinase, lactate dehydrogenase, and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha; the stable metabolite of prostacyclin) were measured during preischemic and reperfusion periods.
RESULTS: After global ischemia, hearts receiving defibrotide in the cardioplegic solution (n = 8) manifested in a concentration-dependent fashion lower left ventricular end-diastolic pressure (p < 0.001), higher left ventricular developed pressure (p < 0.01), and lower coronary perfusion pressure (p < 0.001) compared to the control group. After reperfusion, hearts receiving defibrotide in the cardioplegic solution also had, in a dose-dependent way, lower levels of creatine-kinase (p < 0.01), lactate dehydrogenase (p < 0.001), and higher levels of 6-keto-PGF1alpha (p < 0.001) compared to the control group. Furthermore, when defibrotide was given alone to the hearts at the beginning of reperfusion (n = 7), the recovery of postischemic left ventricular function was inferior (p < 0.05) to that obtained when defibrotide was given in cardioplegia.
CONCLUSIONS: Defibrotide confers to conventional crystalloid cardioplegia a potent concentration-dependent protective effect on the recovery of isolated rat heart undergoing ischemia/reperfusion injury. The low cost and the absence of contraindications (cardiac toxicity and hemodynamic effects) make defibrotide a promising augmentation to cardioplegia.
G Rossoni; G Pompilio; P Biglioli; F Alamanni; P Tartara; P Rona; M Porqueddu; F Berti
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiac surgery     Volume:  14     ISSN:  0886-0440     ISO Abbreviation:  J Card Surg     Publication Date:    1999 Sep-Oct
Date Detail:
Created Date:  2000-07-17     Completed Date:  2000-07-17     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8908809     Medline TA:  J Card Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  334-41     Citation Subset:  IM    
Department of Pharmacology, Chemotherapy and Medical Toxicology, Institute of Pharmacological Science, University of Milan, Italy.
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MeSH Terms
Fibrinolytic Agents / pharmacology*
Heart Arrest, Induced*
Myocardial Reperfusion Injury / pathology,  physiopathology*
Myocardium / pathology
Organ Preservation
Polydeoxyribonucleotides / pharmacology*
Rats, Wistar
Ventricular Function, Left / drug effects
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Polydeoxyribonucleotides; 438HCF2X0M/defibrotide

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