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Prolongation of pig-to-dog renal xenograft survival by modification of the inflammatory mediator response

Makowka, L and Miller, C and Chapchap, P and Podesta, L and Pan, C and Pressley, D and Mazzaferro, V and Esquivel, CO and Todo, S and Banner, B and Jaffe, R and Saunders, R and Starzl, TE (1987) Prolongation of pig-to-dog renal xenograft survival by modification of the inflammatory mediator response. Annals of Surgery, 206 (4). 482 - 495. ISSN 0003-4932

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The pathogenesis of hyperacute renal rejection consists of a nonspecific effector cascade that invokes most of the components of a typical acute inflammatory response. Platelet-activating factor (PAF) represents the most recent and perhaps the most significant mediator and promoting agent of this phenomenon. These studies evaluated SRI 63-441, a novel, synthetic, and the most potent PAF receptor antagonist available, alone and in combination with other prostanoids, for their ability to influence this response and to prolong renal xenograft survival and function in a model of pig-to-dog heterotransplantation. Inhibition of PAF by SRI 64-441 alone, at the dosage and schedule used in these experiments, did not significantly prolong xenograft survival or function. However, the combination of SRI 63-441 with either prostacyclin (PGI2) or prostaglandin E1 (PGE1) infusion demonstrated significant synergism, and resulted in a 6-9-fold increase in kidney survival and a 3-20-fold increase in urine output. Neither PGI2 nor PGE1 infusions alone significantly influenced this xenograft model. Electromagnetic flow studies demonstrated significantly delayed diminution in renal artery blood flow in the combination-treated animals. Serial and end-stage histologic examination of kidneys receiving combination therapy demonstrated a delayed onset of the pathologic deterioration and an overall amelioration of the entire process. These studies demonstrate that significant abrogation of a rapid and violent form of the hyperacute rejection can be achieved solely by the pharmacologic manipulation of the inflammatory mediator response.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Makowka, L
Miller, C
Chapchap, P
Podesta, L
Pan, C
Pressley, D
Mazzaferro, V
Esquivel, CO
Todo, S
Banner, B
Jaffe, R
Saunders, R
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1987
Date Type: Publication
Journal or Publication Title: Annals of Surgery
Volume: 206
Number: 4
Page Range: 482 - 495
DOI or Unique Handle: 10.1097/00000658-198710000-00009
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0003-4932
Other ID: uls-drl:31735062129196, Starzl CV No. 765
Date Deposited: 08 Apr 2010 17:13
Last Modified: 19 Jun 2021 10:55


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