The influence of antibody and complement removal with a Ig-Therasorb column in a xenogeneic working heart model

Objective: Organ transplantation is limited by the number of brain-dead hum an donors. Xenotransplantation could be an alternative to guarantee a const ant supply of organs. A major problem of xenotransplantation are xenogeneic natural antibodies (XNAb) directed against species-specific antigens of a discordant donor species (e.g. pig). They trigger the hyperacute xenograft rejection (HXR). Re-usable immunoapheresis (IA)-columns Ig-Therasorb((R)) ( Therasorb, Baxter) were used to adsorb these XNAb. The effect of immunoaphe resis of the perfusing human blood was investigated in ex vivo working pig hearts. Methods: Hearts of 12 landrace pigs (body weight 14-31 kg) were exp lanted after inducing cardiac arrest with 4 degrees C Celsior solution. Hum an blood (500 ml, heparinized) was obtained from healthy volunteers. In gro up 1 (G1, n = 6), blood as perfusate remained untreated. In group 2 (G2, n = 6), native blood was separated by plasmapheresis into cellular components and plasma. The latter passed through the Ig-Therasorb column for removal of immunoglobulins (so-called immunoadsorption or immunoapheresis). After b ack-table preparation the hearts were mounted to the working heart model. A fter 20 min of reperfusion in Langendorff mode, the working heart mode was established. Blood samples were taken isochronously for measurement of: CK( -MB), LDH, ASAT, troponin, immunoglobulins, complement activity, anti-pig a ntibodies and others. After cessation of the heart, atrial and ventricular tissue samples were taken for histological examinations (light/electron mic roscopy and immunohistochemistry). Results: Two cycles of immunoapheresis r educed the levels of IgG by 84%, IgM by 83.3% and IgA by 76%. In G2, the an tibody immunoadsorption of blood prolonged the duration of the working hear t mode significantly to 335 +/- 37.5 min. In contrast, hearts of group 1 (c ontrol) failed after 125 +/- 31.3 min. Heart rate was significantly differe nt between both groups (G1, 77.3 +/- 6.1 beats/min; G2, 86.5 +/- 5.5 beats/ min). In G2 cardiac output was 118% and mean coronary flow was 154.6% highe r than in G1. CK, LDH and ASAT showed no differences in the two groups. Hea rt weight increased significantly more in group 1 than in G2. Histological examination indicated specific signs of HXR in G1 after 1.5 h, whereas in G 2 only slight unspecific damages were found after 6 h. Conclusion: Antibody removal by means of immunoapheresis results in a significantly improved xe nogeneic cardiac function. Immuno-apheresis may, therefore, become an impor tant adjunct in future pig-to-man clinical xenotransplantation. (C) 1999 El sevier Science B.V. All rights reserved.