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Experimentelle Xenotransplantation in entfernt stammesverwandten Speciessystemen

Beeinflussung der hyperakuten xenogenen Abstoßungsreaktion von Nieren vom Schwein (Spender) durch extreme isovolämische Hämodilution von Hunden (Empfänger)

Experimental xenografting in widely divergent species

Modification of the Hyperacute Xenogeneic Rejection of Kidneys from Pigs (Donor) by Extreme Hemodilution of Dogs (Recipients)

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Research in Experimental Medicine

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Summary

E vivo hemoperfusion of pig kidneys by untreated dogs results in a complete deterioration of function within 15 min caused by a hyperacute xenogeneic rejection. Flush out of these kidneys by a special perfusion solution of 4°C is already able to delay the complete stop of the renal blood flow to approximately 2 hrs.

Preformed natural antibodies together with complement, platelets, white blood cells and vasoactive substances are discussed to be the reason for this type of graft rejection.

Extreme isovolemic hemodilution of the recipient dog with 6% Dextran 60 to a hematocrit of 7.5% eliminates most of the preformed natural antibodies. In parallel, all other factors like complement,γ globulins, thrombocytes and leucocytes are significantly decreased.

The wash out of these factors by gradually replacing whole blood with only Dextran 60 and washed autologous erythrocytes leads to a striking mitigation of the xenogeneic reaction, resulting in a prolongation of the functional survival as indicated by extending the renal blood flow up to 11 hrs and a tremendous increase of urine production.

Zusammenfassung

E vivo-Hämoperfusion von Schweinenieren durch unbehandelte Hunde führt schon nach 15 min zu einem völligen Funktionsausfall der Organe auf Grund der hyperakuten xenogenen Abstoßungsreaktion. Eine Vorperfusion der Nieren mit einer 4°C-Nierenperfusionslösung verzögert das Sistieren des renalen Blutflusses um fast 2 Std.

Präformierte natürliche Antikörper zusammen mit Komplement, Thrombocyten, Leukocyten sowie von vasoaktiven Substanzen werden als auslösende Momente bei dieser Transplantatabstoßung diskutiert.

Extreme isovolämische Hämodilution des Empfängers mit 6% Dextran 60 bis zu einem Hämatokrit von 7,5% eliminiert den größten Teil der präformierten natürlichen Antikörper. Gleichzeitig werden alle anderen Blutbestandteile wie Komplement und Zellen deutlich vermindert.

Die Reduzierung dieser Faktoren durch graduellen Ersatz des Gesamtblutes mit Dextran 60 und gewaschenen autologen Erythrocyten führt zu einer signifikanten Abschwächung der xenogenen Abstoßungsreaktion und damit zu einer Verbesserung der Funktion, die sich in einer Verlängerung der Nierendurchblutungszeit und einem starken Anstieg der Urinproduktion äußert.

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Abbreviations

HXAR:

Hyperakute xenogene Abstoßungsreaktion

RBF:

renaler Blutfluß

KBR:

Komplementbindungsreaktion

KG:

Kontrollgruppe

VG:

Versuchsgruppe

C′:

Komplement

PNAK:

präformierte natürliche Antikörper

HKT:

Hämatokrittiefstwert

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Authors and Affiliations

  1. Institut für chirurgische Forschung, Chirurgischen Klinik der Universität München, Nußbaumstraße 20, D-8000, München 2, Bundesrepublik Deutschland

    L. Fiedler, C. Hammer, K. Messmer, W. Land, K. Holper, W. Klövekorn, K. Pielsticker, C. Chaussy & W. Brendel

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  1. L. Fiedler
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  2. C. Hammer
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  3. K. Messmer
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  4. W. Land
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  6. W. Klövekorn
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  7. K. Pielsticker
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  8. C. Chaussy
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  9. W. Brendel
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Fiedler, L., Hammer, C., Messmer, K. et al. Experimentelle Xenotransplantation in entfernt stammesverwandten Speciessystemen. Res. Exp. Med. 163, 137–153 (1974). https://doi.org/10.1007/BF01856408

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  • DOI: https://doi.org/10.1007/BF01856408

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