Inhibition of platelet aggregation by the GPIIb/IIIa antagonist Reopro does not significantly prolong xenograft survival in an ex vivo model

Abstract

Effects on hyperacute re-better preservation of morphology jection were studied in a discordant model with the platelet GPIIb/IIIa antagonist Reopro. Pig kidneys perfused with human blood survived median 118 min in the Reopro group and 103 min in the controls (P = 0.22). Platelet and leukocyte counts decreased, whereas plasma thrombospondin and soluble as well as platelet membrane P-selectin increased significantly in both groups without significant intergroup differences. P-Thromboglobulin and myeloperoxidase increased significantly more in the control group than in the Reopro group ( P = 0.009 and P = 0.02, respectively). The classical complement pathway was substantially and similarly activated in both groups. Light and electron microscopy revealed arterial thrombi and numerous glomerular platelet aggregates in the control group in contrast to the Reopro group. In conclusion, Reopro reduced platelet aggregation, and platelet and leukocyte activation to some extent, but had no effect on complement activation and did not significantly prolong xenograft survival, even though was shown.

Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation

“…demonstrated prolonged xenograft survival and diminution of intragraft platelet microthrombi using the GPIIb/IIIa antagonist GPI 562. These results were not confirmed in a more recent ex vivo discordant perfusion model of a porcine kidney with human blood using the GPIIb/IIIa antagonist abciximab [61]. In this model, however, as no measures were undertaken to prevent hyperacute rejection, the effect of inhibition of platelet aggregation posthyperacute rejection was not addressed.…”

Prolongation of ex vivo–perfused pig xenograft survival by the complement inhibitor compstatin

“…Kidneys were removed using sterile procedures, and the ex vivo perfusion system has previously been described in detail. 4 Compstatin (ICVVQDWGHHRCT-NH 2 ), a cyclic peptide of 1551 D, has been extensively described previously. 3 Heparinized fresh AB whole blood was drawn from informed, healthy human volunteers.…”

Literature update 1999, part 3

“…Fiane and colleagues did not find a therapeutic benefit of using a GPIIb/IIIa antagonist to inhibit platelets [42], but they did show a benefit with a complement C1‐inhibitor [43] and C3 inhibitor [44] and Wang et al. showed a benefit with a C5 inhibitor [45].…”