caa a22 4500 477119662 CHVBK 20180405111632.0 cr unu---uuuuu 170330e19960301xx s 000 0 eng 10.1007/BF00240065 doi (NATIONALLICENCE)springer-10.1007/BF00240065 Xenoreactive natural antibodies and induced antibodies — their effects on beating cardiomyocytes as a model of a xenograft [Elektronische Daten] [Ursula Müller-Werdan, Bernd Koidl, Arnd Autenrieth, Dieter Klein, Karl Werdan, Claus Hammer] Xenotransplantation has been complicated by hyperacute rejection reactions, which are supposedly triggered by preformed natural antibodies (PNAb) of the recipient organism, whereas the role of antibodies specifically induced by previous antigen contact (IAb) is less clear. Primary cultures of spontaneously beating neonatal rat cardiomyocytes were used as a model of the heart to elaborate the effects of both PNAb and IAb from xenogeneic species and to investigate into their mechanisms of action. An experimental setup allowing for rapid medium exchange under continuous observation was employed. Sera containing PNAb reproducibly bring about a stereotype pattern of altered contractility including an initial increase in beating frequency followed by a temporary cessation of beating within the first minutes after administration. After recovery of spontaneous contractions, the cells within the monolayer exhibited a dissociation of the synchronicity of the beating persisting for several hours. The temporary pause in beating was prevented by a very high extracellular calcium concentration, but not by extracellular electrical stimulation sufficient to trigger contractions in control cells. Electrophysiological measurements carried out in adult ventricular guinea pig heart muscle cells under the same experimental conditions revealed an increase of the excitation threshold of the cells after application of sera containing PNAb due to an enhanced input resistance. These results indicate that the effect of PNAb is the consequence rather of a generally reduced excitability of the cell than of the inhibition of a singular ionic conductance. After specific absorption of PNAb directed against rat antigens beating of neonatal rat cardiomyocytes ensued without interruption. Sera specimens devoid of complement produced similar effects on contractility, although the duration of the standstill period was significantly shorter. The increase in input resistance visualized in guinea pig myocytes was absent after removing PNAb against guinea pig antigens but not after absorbing PNAb directed against rat epitopes. Signs of a permanent cytotoxicity after the administration of PNAb were lacking in all experiments. IAb against rat heart tissue raised in rabbits stopped the contractions of neonatal rat cardiomyocytes within 30 min after administration irreversibly and lead concentration-dependently to a destruction of the cells. (Mol Cell Biochem 160/161: 315-324, 1996) Kluwer Academic Publishers, 1996 antibodies nationallicence neonatal rat cardiomyocytes nationallicence hyperacute rejection reaction nationallicence electrophysiology nationallicence xenotransplantation nationallicence contractility nationallicence complement nationallicence Müller-Werdan Ursula Department of Internal Medicine III, University of Halle-Wittenberg, Klinikum Kröllwitz, Ernst-Grube-Stra⌆ 40, D-06097, Halle, Germany aut Koidl Bernd Institute for Medical Physics and Biophysics, University of Graz, Harrachgasse 21, A-8010, Graz, Austria aut Autenrieth Arnd Department of Experimental Surgery, University of Munich, Klinikum Grofβhadern, Marchioninistraβe 15, D81377, München, Germany aut Klein Dieter Department of Experimental Surgery, University of Munich, Klinikum Grofβhadern, Marchioninistraβe 15, D81377, München, Germany aut Werdan Karl Department of Cardiac Intensive Care Medicine, University of Halle-Wittenberg, Klinikum Kröllwitz, Ernst-Grube-Straβe 40, D-06097, Halle, Germany aut Hammer Claus Department of Experimental Surgery, University of Munich, Klinikum Grofβhadern, Marchioninistraβe 15, D81377, München, Germany aut Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 160-161/1(1996-03-01), 315-324 0300-8177 160-161:1<315 1996 160-161 11010 https://doi.org/10.1007/BF00240065 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00240065 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Müller-Werdan Ursula Department of Internal Medicine III, University of Halle-Wittenberg, Klinikum Kröllwitz, Ernst-Grube-Stra⌆ 40, D-06097, Halle, Germany aut NATIONALLICENCE 700 1- Koidl Bernd Institute for Medical Physics and Biophysics, University of Graz, Harrachgasse 21, A-8010, Graz, Austria aut NATIONALLICENCE 700 1- Autenrieth Arnd Department of Experimental Surgery, University of Munich, Klinikum Grofβhadern, Marchioninistraβe 15, D81377, München, Germany aut NATIONALLICENCE 700 1- Klein Dieter Department of Experimental Surgery, University of Munich, Klinikum Grofβhadern, Marchioninistraβe 15, D81377, München, Germany aut NATIONALLICENCE 700 1- Werdan Karl Department of Cardiac Intensive Care Medicine, University of Halle-Wittenberg, Klinikum Kröllwitz, Ernst-Grube-Straβe 40, D-06097, Halle, Germany aut NATIONALLICENCE 700 1- Hammer Claus Department of Experimental Surgery, University of Munich, Klinikum Grofβhadern, Marchioninistraβe 15, D81377, München, Germany aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 160-161/1(1996-03-01), 315-324 0300-8177 160-161:1<315 1996 160-161 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer