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Protectant Activity of Defibrotide in Cardioplegia Followed by IschernialReperfusion Injury in the Isolated Rat Heart
Author(s) -
Rossoni Giuseppe,
Pompilio Giulio,
Biglioli Paolo,
Alamanni Francesco,
Tartara Paolo,
Rona Paolo,
Porqueddu Massimo,
Berti Ferruccio
Publication year - 1985
Publication title -
echocardiography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.404
H-Index - 62
eISSN - 1540-8175
pISSN - 0742-2822
DOI - 10.1111/j.1540-8175.1985.tb01302.x
Subject(s) - defibrotide , prostacyclin , medicine , ischemia , creatine kinase , cardiology , lactate dehydrogenase , cardioprotection , reperfusion injury , anesthesia , iloprost , chemistry , biochemistry , transplantation , enzyme , hematopoietic stem cell transplantation
Background: Previous studies have shown that defibrotide, a polydeoxyribonu‐cleotide 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 pg/mL) or without defibrotide (controls). Left ventricular mechanical function and the levels of creatine kinase, lactate dehydrogenase, and 6‐keto‐prostaglandin F 1α (6‐keto‐PGF 1α ; 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<0·011, and lower coronary per‐fusion 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<0·011, lactate dehydrogenase (p<0·0011, and higher levels of 6‐keto‐PGF 1α (p<0·0011 compared to the control group. Furthermore, when defibrotide was given alone to the hearts at the beginning of reperfusion (n = 71, 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.