Aktivierung von Granulozyten und Antiproteasen bei herzchirurgischen Eingriffen mit extrakorporaler Zirkulation

 

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Zusammenfassung

Ziel der Studie: Eingriffe am offenen Herzen unter extrakorporaler Zirkulation (EKZ) induzieren die Aktivierung von neutrophilen Granulozyten. Die Freisetzung von Proteasen und reaktiven Sauerstoffmetaboliten im Rahmen dieser Aktivierung kann eine kausale Rolle bei der Entstehung von Krankheitsprozessen in der postoperativen Phase darstellen, wenn die körpereigenen Schutzmechanismen durch Antiproteasen und Antioxidanzien dabei überwunden werden. In dieser Studie wurde deshalb der Einfluss von herzchirurgischen Eingriffen mit EKZ auf die Mediatoren neutrophiler Granulozyten untersucht. Es wurden die Plasmaspiegel von Neutrophiler Elastase (NE) und ihren Inhibitoren α₁-Proteinase-Inhibitor (API) und Secretory Leukocyte Proteinase Inhibitor (SLPI) bestimmt. Weiterhin wurden Phagozytoseaktivität und Oxidativer Burst ermittelt. Zur Quantifizierung der Gewebedestruktion wurde die Konzentration an Fibronektin im Serum bestimmt. Methodik: Blutproben von 30 Patienten, die sich einer aortokoronaren Bypass-Operation unterzogen, wurden zu definierten Zeitpunkten vor, während und nach der Operation gewonnen. Die API- und Fibronektin-Plasmaspiegel wurden nephelometrisch, die SLPI- und NE-Konzentrationen mittels ELISA bestimmt. Die Bestimmung von Phagozytoseaktivität und Oxidativem Burst in neutrophilen Granulozyten erfolgte mittels Durchflusszytometrie. Ergebnisse: Während die Plasmaspiegel von NE während der EKZ signifikant (245 ± 107 µg/ml versus 44 ± 14 µg/ml nach Narkoseeinleitung, p < 0,001) erhöht waren, kam es zu einem Abfall der API- und SLPI-Konzentrationen in diesem Zeitraum. Im Vergleich zu den Ausgangswerten waren API (3 ± 0,5 g/l versus 1,6 ± 0,3 g/l, p < 0,05) und SLPI (54 ± 17 ng/ml versus 41 ± 10 ng/ml, p < 0,05) in der postoperativen Phase erhöht. Die Phagozytoseaktivität war während der EKZ nur geringfügig erhöht, der Oxidative Burst zeigte ebenfalls keine signifikanten Änderungen. Schlussfolgerung: Kardiochirurgische Eingriffe unter Einsatz der EKZ induzieren eine signifikante Freisetzung von NE bei fehlendem Anstieg der Proteaseinhibitoren. Die Dysbalance zwischen NE und den Antagonisten API und SLPI könnte gewebeschädigende Effekte durch aktivierte Granulozyten nach herzchirurgischen Eingriffen begünstigen.

Abstract

Objective: Cardiovascular surgical procedures with extracorporeal circulation (ECC) lead to neutrophil activation followed by the release of proteases such as neutrophil elastase (NE) and oxidants. The misbalance between proteases and their physiological inhibitors may contribute to morbidity in the postoperative period. In this study, the effects of cardiac surgery on neutrophil mediators were evaluated. Release of neutrophil elastase and plasma levels of the natural NE antagonists α₁-proteinase inhibitor (API) and secretory leukocyte proteinase inhibitor (SLPI) were measured. The oxidative burst and the phagocytic activity were also evaluated. Tissue destruction was quantified by measuring the serum concentration of fibronectin. Methods: Blood samples were obtained from 30 patients undergoing elective coronary artery bypass grafting (n = 30). NE and SLPI concentrations were measured by ELISA, API and fibronectin plasma levels were determined by nephelometry. Neutrophil phagocytic activity and oxidative burst were evaluated by flow cytometry. Results: Neutrophil elastase plasma concentrations rose during ECC (245 ± 107 µg/ml versus 44 ± 14 µg/ml after induction, p < 0.001), whereas SLPI and API were decreased after onset of ECC. 24 h after ECC SLPI (54 ± 17 ng/ml versus 41 ± 10 ng/ml, p < 0.05) and API (3 ± 0.5 g/l versus 1.6 ± 0.3 g/l, p < 0.05) increased significantly compared to baseline values. A minor increase in phagocytic activity was observed after the onset of ECC. There were no significant changes in the oxidative burst. Conclusion: Cardiac surgery with ECC leads to neutrophil activation and elastase release. The imbalance between NE and the NE inhibitors API and SLPI may increase the risk for tissue damage due to granulocyte activation after cardiac surgery.

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PD Dr. med. Ingeborg Welters

Abteilung für Anaesthesiologie und Operative Intensivmedizin, Klinikum der Justus-Liebig-Universität Gießen

Rudolf-Buchheim Straße 7 · 35385 Gießen ·

Email: Ingeborg.D.Welters@chiru.med.uni-giessen.de