The PAF antagonist TCV-309 reduces graft PMN infiltration and enhances early function of 24-hour-preserved rat kidneys with long warm ischemia.
The purpose of this study was to investigate whether treatment with TCV-309, a PAF antagonist, improves life-sustaining function of renal grafts that have suffered warm ischemia (WI) prior to cold storage (CS) and whether TCV-309 influences leukocyte sequestration in tissues. Syngeneic kidneys with 20 min of WI and 24 hr of CS were transplanted into bilateral nephrectomized rats. In the treated group, TCV-309 was administered (i.v. 1 mg/kg) 5 min before reperfusion. Rats in the control group received saline. On day 14, 80% rats survived in the treated group, which was higher than the controls (0%). At 24 hr of reperfusion, myeloperoxidase (MPO) activity, a marker enzyme for PMNs, in the treated kidney was significantly lower than the controls, but did not differ from the normal values. The MPO activity in the controls was higher than the normal values. In conclusion, the PAF antagonist improves posttransplant function of rat kidneys subjected to a period of WI and CS. PMNs are involved in postischemic renal injury, which is, at least partially, mediated by PAF. The effectiveness of PAF antagonist in treatment of recipients may lead to its clinical application in transplantation of ischemically injured kidneys.
Yin
M
M
Department of Surgery, University Hospital Maastricht, The Netherlands.
Buurman
W A
WA
Daemen
J W
JW
Kootstra
G
G
D000818:Animals; D006358:Hot Temperature; D007111:Immunity, Cellular / Q000187:drug effects; D007511:Ischemia; D007546:Isoquinolines / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D007672:Kidney Cortex / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods* / Q000473:pathology; D008168:Lung / Q000201:enzymology; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000276:immunology*; D009926:Organ Preservation; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D044005:Tetrahydroisoquinolines; D013997:Time Factors
D007546:Isoquinolines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; D009195:Peroxidase; C067430:TCV 309