Prostacyclin release from endothelial cells, induced by defibrotide treatment, favours the function of grafted rat hearts and kidneys.
Defibrotide, a single-stranded DNA fraction obtained from mammalian lungs and able to increase prostacyclin production by endothelial cells, has been shown to be efficient in protecting rat organs (heart, kidney and liver) from ischaemic damage. We studied the efficacy of the drug in preserving the function of rat heart and kidney submitted to isotransplantation. Defibrotide was administered to donor Wistar rats at the dose of 32 mg/kg in 1.5 ml of saline. Heart and kidney were isolated and cold-preserved in buffered phosphate medium and continuously infused with defibrotide (32 mg/h) through the innominate or renal artery. Recipient Wistar rats were treated with defibrotide before and after transplantation at the dose of 32 mg/kg/day. Controls were treated with the vehicle of the drug. The function of isografted organs was evaluated at 12 and 24 h and at 2, 4 and 7 days from grafting. Heart function was evaluated by studying creatinine phosphokinase (CPK) and lactic dehydrogenase (LDH) activities of myocardial tissue. Renal function was evaluated by studying serum creatinine and urea levels of kidney-grafted rats. CPK and LDH activities were found to be significantly higher in defibrotide-treated rats than in controls. Creatinine and urea levels remained significantly lower in defibrotide-treated rats than in the controls. The results of the present work indicate that defibrotide treatment is useful to maintain the functionality of grafted hearts and kidneys.
Ferrero
M E
ME
Instituto di Patologia Generale, Università degli Studi di Milano, Italy.
Marni
A
A
Salari
P C
PC
Spaggiari
P G
PG
Gaja
G
G
D000818:Animals; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D016027:Heart Transplantation / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D011464:Epoprostenol