BEATING NEONATAL RAT CARDIOMYOCYTES AS A MODEL TO STUDY THE ROLE OF XENOREACTIVE NATURAL ANTIBODIES IN XENOTRANSPLANTATION

The hyperacute rejection reaction of xenogeneic organs is supposed to be triggered by xenoreactive natural antibodies of the recipient organ ism. In an experimental set-up allowing for rapid medium exchange, pri mary cultures of spontaneously beating neonatal rat cardiomyocytes wer e challenged with dialyzed human serum containing xenoreactive natural antibodies. After adding the serum specimens, a reproducible pattern of disturbed contractility was observed: following an initial increase in beating frequency, spontaneous contractions stopped completely. Th is standstill was reversible in all experiments. No signs of permanent cytotoxicity were observed. The temporary cessation of contractions w as prevented by raising extracellular calcium concentration, but not b y extracellular electrical stimulation. After absorption of xenoreacti ve natural antibodies, cellular contractions ensued without interrupti on. Inactivated serum specimens produced similar effects on contractil ity, although the duration of the standstill period was significantly shorter. The same qualitative phenomenon occurred when sera of other x enogeneic species were used. These results point to a temporary functi onal disturbance of parenchymal cells by xenoreactive natural antibodi es, whereas no chronic cytotoxicity was conspicuous in these experimen ts.