Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants.
Hyperacute rejection is a serious complication of xenogeneic organ transplantation. It is believed that platelets play a pivotal role in this phenomenon. In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts. Transplantation of guinea pig hearts into recipient rats resulted in hyperacute rejection. Pretreatment of recipient animals with tulopafant (but not indomethacin) extended rejection time by 4-5-fold. Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant.
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226.
D P
DP
O'Hair
A M
AM
Roza
R
R
Komorowski
G
G
Moore
R P
RP
McManus
C P
CP
Johnson
M B
MB
Adams
G M
GM
Pieper
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects*; D006168:Guinea Pigs; D016027:Heart Transplantation; D008297:Male; D010980:Platelet Membrane Glycoproteins; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D014183:Transplantation, Heterologous; D014654:Vascular Patency / Q000187:drug effects*
D010980:Platelet Membrane Glycoproteins; D011725:Pyridines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; C039351:platelet activating factor receptor; C065022:RP 59227