Asunto(s)
Antígenos de Diferenciación/uso terapéutico , Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Inmunoconjugados , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Trasplante Heterólogo/inmunología , Abatacept , Animales , Antígenos CD , Linfocitos B/inmunología , Antígeno CTLA-4 , Cricetinae , Enfermedad Injerto contra Huésped/inmunología , Activación de Linfocitos , Ratas , Ratas Endogámicas Lew , Esplenectomía , Linfocitos T/inmunología , Factores de Tiempo , Irradiación Corporal TotalAsunto(s)
Bicarbonatos/sangre , Trasplante de Hígado/fisiología , Trasplante Heterólogo/fisiología , Animales , Dióxido de Carbono/sangre , Proteínas Inactivadoras de Complemento/uso terapéutico , Venenos Elapídicos/uso terapéutico , Supervivencia de Injerto , Cobayas , Concentración de Iones de Hidrógeno , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Presión Parcial , Ratas , Ratas Endogámicas Lew , Tacrolimus/uso terapéutico , Trasplante Heterólogo/inmunologíaRESUMEN
Guinea-pig livers are poorly reperfused when transplanted into rats. We have observed that, in contrast to that of the rat, the guinea-pig intrahepatic portal vein (PV) has a thick layer of smooth muscle. It is possible that, after perfusion of the liver with ice-cold saline, this could go into spasm, resulting in poor reperfusion. To test this hypothesis, guinea-pig livers were perfused with different solutions stored at varying temperatures and transplanted into LEW rats. To prevent xenograft hyperacute rejection, all xenograft recipients were treated with 80 U/kg cobra venom factor (CVF) i.v. on days -1 and 0. In addition to the percentage reperfusion, PV resistance and recipient survival were also monitored. In group I, liver xenografts perfused with ice-cold saline (4 degrees C) reperfused poorly (20-30%), resulting in the development of portal hypertension (16.5 cmH2O vs. 12 cmH2O in naive LEW rats) and shortened mean survival time (11.7 +/- 4.2 h). In contrast, group II livers perfused with saline at room temperature (23 degrees C) underwent homogeneous reperfusion (98-100%) with no increase in portal vein resistance, indicating that low temperature was the main trigger for the spasm of the PV. Moreover, recipient survival in this group was significantly prolonged to a mean of 22 + 2.6 h (P < 0.01). Although UW solution (group III) and the vasodilator sodium nitroprusside (NP) (group IV) when used alone improved the degree of hepatic reperfusion, it was still not optimal. The supplementation, however, of UW solution with NP in group V animals resulted in homogeneous reperfusion (98%) with no portal hypertension and consistent prolonged graft survival of 21.0 +/- 1.7 h. Therefore, this study has determined that the riddle of the abnormal reperfusion of guinea-pig liver xenografts by rat blood is nonimmune mediated and is due to the spasm of the strong smooth muscle in the PV tree produced by cold perfusates.