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Aktivierung neutrophiler Granulozyten während Ischämie der Lunge und Reperfusion nach Transplantation: Effekt der Konservierungslösungen Euro-Collins und Low-Potassium-Dextran

Neutrophil activation during ischemia and reperfusion after lung transplantation

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Zeitschrift für Herz-, Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Hauptursache der frühen Morbidität und Mortalität nach Lungentransplantation ist das primäre Transplantatversagen hervorgerufen durch einen Ischämie-Reperfusions-Schaden. Am Modell der allogenen orthotopen unilateralen Lungentransplantation am Schwein haben wir den Einfluß der Lungenkonservierung mit Euro Collins- oder Low-Potassium-Dextran (LPD) Lösung auf den Ischämie-Reperfusions-Schaden und die Aktivierung neutrophiler Granulozyten (PMN) untersucht. Spender- und Empfängertiere wurden in 3 experimentelle Gruppen randomisiert. EC-Gruppe (n=6): In situ Flush-Perfusion mit modifizierter Euro-Collins (EC) Lösung: EC+PTX-Gruppe (n=6): Perfusion mit EC unter Zusatz von Pentoxifyllin (300 mg/l) zur Inhibierung der Leukozytenaktivierung; LPD-Gruppe (n=6): Flush-Perfusion mit LPD (Perfadex) Lösung (100 ml/kg). Nach 18 h Ischämie (4 °C) wurde eine linksseitige unilaterale Transplantation durchgeführt und während 6 h Reperfusion die Lungenfunktion gemessen. Der oxidative Lungenschaden, quantifiziert anhand der Lipidperoxidation (Thiobarbitursäure-reaktive Substanzen (TBARM) in der bronchoalveolären Lavage) und die Ausbildung eines Lungenödems, gemessen als Lungenfeucht/Lungentrockengewichts-Verhältnis (W/D ratio) am Ende der 6stündigen Reperfusion waren sowohl in der EC+PTX als auch in der LPD-Gruppe signifikant geringer als in der EC-Gruppe. Die Transplantatfunktion (arterieller PO2) war signifikant besser bei EC+PTX-konservierten Lungen als nach EC-Konservierung. Wir schließen aus unseren Ergebnissen: (1) Die Aktivierung neutrophiler Granulozyten spielt eine zentrale Rolle für die Ausbildung eines Ischämie-Reperfusions-Schadens nach Lungentransplantation. (2) Lungenkonservierung mit LPD-(Perfadex) Lösung resultiert in einer verminderten Leukozytenaktivierung und einem geringeren Ischämie-Reperfusions-Schaden nach Lungentransplantation.

Summary

The impact of pulmonary vascular flush preservation with Eurocollin’s (EC) solution or low-potassium-dextran (LPD) solution (Perfadex®) on ischemia reperfusion-injury after lung transplantation and the contribution of PMN leukocytes were assessed in an animal model of left-sided orthotopic single lung transplantation. Eighteen pairs of domestic pigs were randomized into three experimental groups: In the EC group (n=6) donor lungs were in situ flush perfused with modified EC solution; in the EC+PTX group (n=6), 300 mg/l of pentoxifylline (PTX) was added to the EC flush solution, and 12 mg/kg of PTX were injected intravenously shortly before reperfusion to inhibit PMN activation; in the LPD group (n=6) low potassium dextran solution (Perfadex®, 100 ml/kg) was used for flush. The duration of cold lung storage was 18 hours. After reimplantation recipient animals were monitored during 6 h of reperfusion. Lung oxidant injury, as evidenced by increased lung wet/dry weight ratios (p<0.05, ANOVA), and lung lipid peroxidation (p<0.01), and PMN accumulation in broncho-alveolar lavage (BAL) fluids (p<0.05) during reperfusion were lower in both the EC+PTX and LPD groups as compared to the EC group. This was paralleled by significantly improved graft function (PaO2) in both the EC+PTX and LPD groups as compared to the EC group (p<0.05). In summary, our results showed that (1) PMN contribute significantly to lung injury during reperfusion following ischemia and lung transplantation, and (2) LPD-preserved lungs as compared to EC-preserved lungs show reduced PMN activation and better early graft function after lung transplantation. Our results suggest that the use of LPD-flush perfusion for lung preservation may result in a reduced incidence of lung ischemia-reperfusion injury after lung transplantation.

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Authors and Affiliations

  1. Chirurgische Klinik und Poliklinik Klinikum Großhadern, Ludwigs-Maximilians-Universität, 81366, München

    H. Hoffmann, C. Müller, F. Sakamaki, C. Daum & F. W. Schildberg

  2. Institut für Chirurgische Forschung Klinikum Großhadern, Ludwig-Maximilians-Universität, 81366, München

    K. Meßmer

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  1. H. Hoffmann
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  2. C. Müller
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  6. F. W. Schildberg
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Hoffmann, H., Müller, C., Sakamaki, F. et al. Aktivierung neutrophiler Granulozyten während Ischämie der Lunge und Reperfusion nach Transplantation: Effekt der Konservierungslösungen Euro-Collins und Low-Potassium-Dextran. Z. Herz-, Thorax-, Gefäßchir. 11, 108–114 (1997). https://doi.org/10.1007/BF03042633

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