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Eur J Cardiothorac Surg 2000;18:589-593
© 2000 Elsevier Science NL


Endothelial apoptosis is induced by serum of patients after cardiopulmonary bypass

Hermann Aeberta, Sylvia Kirchnerb, Andreas Keysera, Dietrich E. Birnbauma, Ernst Hollerb, Reinhard Andreesenb, Günther Eissnerb

a Department of Thoracic and Cardiovascular Surgery, Regensburg University Hospital, Regensburg, Germany
b Department of Internal Medicine I, Division of Hematology and Oncology, Regensburg University Hospital, Regensburg, Germany

Received 8 September 1999; received in revised form 20 July 2000; accepted 22 August 2000.

Corresponding author. Department of Surgery, Division of Thoracic and Cardiovascular Surgery, Eberhard-Karls-Universität Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany. Tel.: +49-7071-298-6638; fax: +49-7071-294-047
e-mail: hermann.aebert{at}med.uni-tuebingen.de

Objective: Increased serum levels of a multitude of mediators like interleukins, tumor necrosis factor, elastase, adhesion molecules, and endotoxin have been described following cardiopulmonary bypass (CPB). The biological consequences of this complex response are unclear. Methods: Serum samples of nine patients scheduled for elective coronary artery bypass grafting were obtained preoperatively and 1, 6, and 12 h after weaning from CPB. Additional serum samples were obtained perioperatively from four patients undergoing major lung resection and from four healthy volunteers. The apoptosis-inducing activity of serum samples on endothelial cells was examined using a tissue culture assay system. Endothelial cells were derived from human umbilical cords and incubated for 48 h with serum samples in various dilutions during their second passage. The culture plates were fixed with methanol/acetone and stained with the DNA dye diamidinophenylindole. Apoptotic and normal cells were identified and counted using phase contrast and fluorescence microscopy. Results: The proportion of apoptotic endothelial cells was 5.6-fold higher in culture plates incubated with diluted (30%) serum samples obtained at 6 h after weaning from CPB when compared to plates incubated with preoperative samples (P=0.0077). A smaller effect occurred already at 1 h in some patients, whereas at 12 h after weaning from CPB no increased endothelial apoptosis was observed. No proapoptotic activity was found in preoperative as well as in control samples from patients undergoing lung resection or from healthy volunteers. Conclusions: Serum of patients after CPB exerts a strong apoptosis inducing activity on human endothelial cells. Apoptotic death of endothelial cells following CPB may be responsible for postoperative vascular and bypass dysfunction including phenomena like increased capillary permeability.

Key Words: Apoptosis • Endothelial cells • Cardiopulmonary bypass




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