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.
Schlüsselwörter
Neutrophile Granulozyten - Proteasen-Antiproteasen-Gleichgewicht - Elastase - secretory
leukocyte proteinase inhibitor - α1-proteinase-inhibitor - extrakorporale Zirkulation - aortokoronare Bypasschirurgie
Key words
Neutrophils - protease-antiprotease-relation - elastase - secretory leukocyte proteinase
inhibitor - α1-proteinase-inhibitor - extracorporeal circulation - coronary artery bypass grafting
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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
