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• W2031569503 abstract "Background. Hyperacute rejection (HAR) of pig-to-primate discordant xenografts is caused by the deposition of preexisting natural antibodies that recognize Galα1-3Gal (αGal)-terminating oligosaccharides on glycoproteins and glycolipids, followed by complement-mediated lysis of the graft's endothelium. In vitro, these natural xenoantibodies can be blocked byαGal-containing oligosaccharides. We undertook in vivo pig-to-baboon cardiac xenotransplantation experiments to evaluate free oligosaccharides as inhibitors of HAR. Methods. Initial 15-min intravenous infusions of αGal-oligosaccharides into baboons were used to measure pharmacokinetic parameters, and to assess the extent of neutralization of anti-αGal antibody activity. αGal trisaccharide (Galα1-3Galβ1-4GlcNAc) or pentasaccharide(Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc) was administered at 0.5 mmol/kg into baboons. Next, two baboons that received porcine heterotopic heart xenografts were continuously infused with αGal pentasaccharide for 4-5 hr, maintaining the serum oligosaccharide concentration in the millimolar range. Results. Pharmacokinetic analysis indicated that the oligosaccharides were rapidly cleared from the blood, with a serum half-life of 50 min. In the period during which blood oligosaccharide concentration was above 1 mM, as determined by high-pressure liquid chromatography, the serum cytotoxic activity against porcine cells was completely abolished. HAR of the xenograft was inhibited during the infusions, although there was some histological and immunohistological evidence of antibody-mediated injury on biopsies taken at the end of this period. Conclusions. Intravenous αGal oligosaccharides, by inhibiting anti-αGal antibody activity, delay but do not abolish the onset of HAR." @default.
• W2031569503 created "2016-06-24" @default.
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• W2031569503 date "1998-02-01" @default.
• W2031569503 modified "2023-10-18" @default.
• W2031569503 title "INTRAVENOUS INFUSION OF Gal??1-3Gal OLIGOSACCHARIDES IN BABOONS DELAYS HYPERACUTE REJECTION OF PORCINE HEART XENOGRAFTS" @default.
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• W2031569503 doi "https://doi.org/10.1097/00007890-199802150-00009" @default.
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