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Eur J Cardiothorac Surg 2003;24:932-939
© 2003 Elsevier Science NL


Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation

Serban C. Stoicaa, Duwarakan K. Satchithanandaa, Carl Atkinsonb, Susan Charmanc, Martin Goddardb, Stephen R. Largea*

a Department of Transplantation, Papworth Hospital, Cambridge, UK
b Department of Pathology, Papworth Hospital, Cambridge, UK
c Department of Statistics, Papworth Hospital, Cambridge, UK

Received 19 April 2003; received in revised form 30 June 2003; accepted 3 July 2003.

* Corresponding author. Papworth Hospital, Cambridge, CB3 8RE, UK. Tel.: +44-1480-830541; fax: +44-1480-364334
e-mail: stephenrlarge{at}hotmail.com

Objective: Solid organ transplantation is associated with activation of apoptotic pathways and other stress markers. We aimed to describe the expression of Bax, Bcl-2, iNOs and Hsp-70 in the endothelium and myocytes of both ventricles and to see if there is any relationship with clinical donor organ failure. Methods: Twelve patients undergoing heart or heart–lung transplantation (including three domino cases) were studied with transmural biopsies from the right (RV) and the left ventricles (LV) at the following points: after donor optimisation; at the end of ischaemic time; and after 10 min of reperfusion. The 1-week endomyocardial RV biopsy was also examined. Five donor hearts turned down purely on functional grounds were analysed also. Results: There was no difference between the RV and the LV for any of the markers at intraoperative assessment. The pattern of expression was not predictive of allograft failure. Donor hearts, however, have a strong pro-apoptotic phenotype, which is largely unopposed by the protective factors Bcl-2 and Hsp-70. Furthermore, the intensity of myocyte staining increases over time for Bax (P<0.001) and iNOs (P=0.02). Domino hearts showed a similar pattern. Compared to usable organs, poorly functioning donor hearts have stronger myocardial staining for Bax (P=0.002) and iNOs (P=0.01). Conclusions: Clinical cardiac transplantation is associated with activation of the Bax and iNOs pathways in both ventricles. The myocardium is affected in time-dependent fashion but this is compatible, to a certain extent, with satisfactory allograft function. Donor hearts turned down on the basis of poor haemodynamic performance have significantly higher expression of Bax and iNOs.

Key Words: Cardiac transplantation • iNOs • Heat shock protein • Apoptosis




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