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Eur J Cardiothorac Surg 2007;32:639-643. doi:10.1016/j.ejcts.2007.06.041
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Inducible NO synthase expression in endomyocardial biopsies after heart transplantation in relation to the postoperative course

^a Department of Cardiac Surgery, University of Heidelberg, Germany
^b Institute of Pathology, University of Heidelberg, Germany
^c Department of Cardiology, Theresien-Hospital, Mannheim, Germany

Received 22 March 2007; received in revised form 21 June 2007; accepted 27 June 2007.

^_* Corresponding author. Address: Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. Tel.: +49 6221 5636191; fax: +49 6221 565585. (Email: achim_koch{at}med.uni-heidelberg.de).
^_** Corresponding author. Address: Department of Cardiology, Theresien-Hospital, Bassermannstr. 1, D-68167 Mannheim, Germany. (Email: achim_koch{at}med.uni-heidelberg.de).

Objective: Ischemia and reperfusion during heart transplantation cause damage to cardiomyocytes and endothelial cells and may initiate later acute rejection. Free oxygen radicals generated by iNOS are widely accepted to be responsible for ischemic injury. Increased iNOS expression on cardiac tissue may represent a more intensive tissue injury during ischemia and reperfusion in heart transplantation. The aim of this study was, therefore, to test the hypothesis that increased iNOS expression in early postoperative endomyocardial biopsies correlates with rejection or infection episodes in the later postoperative course. Patients and methods: Right ventricular endomyocardial biopsies were obtained from heart transplantation recipients at transplantation and during the first 2 weeks postoperatively. The recipients were divided into three groups depending on the postoperative course during the first year after transplantation: patients in group 1 had an uncomplicated postoperative course, patients in group 2 developed significant signs of postoperative infection, while patients in group 3 presented with acute rejection (grade 2R ISHLT). The expression was analyzed in a semi-quantitative score. Results: iNOS expression was found in cardiomyocytes, endothelial cells, infiltrating cells, and vascular smooth muscle cells. At the time of heart transplantation, the expression was significantly increased in the rejection group compared to the other groups. This increase was even more pronounced in week 2. Conclusions: The present study shows that an increased iNOS expression at the time of heart transplantation could precede an acute rejection in the later postoperative course. Thus, measurements of iNOS expression may be of predictive value for an increased rejection risk and therefore offer the possibility of earlier therapeutic intervention.

Key Words: Heart transplantation • Rejection iNOS expression

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