Impact of apoptosis in acute rejection episodes after heart transplantation: immunohistochemical examination of right ventricular myocardial biopsies.
OBJECTIVE
Acute rejection may lead to cell death following heart transplantation. Programmed cell death (apoptosis) has been described as a cofactor for cell loss in cardiac tissue. The aim of our study was to quantify the amount and extent of apoptotic cells during acute rejection episodes after orthotopic heart transplantation.


METHODS
Right ventricular biopsies from 27 heart transplant recipients were classified histologically according to rejection grade. Formalin-fixed sections were processed for immunohistochemistry. TUNEL-positive cells were counted and the expression of apoptosis-modulating factors Bax, Bcl-x(L), Bcl-2, and Ki-67 (proliferation marker) was scored. P <or= .05 was considered statistically significant.


RESULTS
The total amount of TUNEL-positive interstitial cells was 1.5/mm(2) and 1/mm(2) for cardiomyocytes. The number of TUNEL-positive interstitial cells was found to be significantly higher in high-grade rejection. The anti-apoptotic Bcl-2 was expressed significantly higher in interstitial cells during high-grade rejection, whereas in cardiomyocytes there were no differences regarding Bcl-2 expression. There were no significant differences in the expression of Bcl-x(L) and Bax. The proliferation marker Ki-67 was not positive in cardiomyocytes. In interstitial cells the expression did not differ between low-and high-grade rejection.


CONCLUSIONS
The current study demonstrated the presence of apoptotic cell death during acute rejection episodes in human heart transplants. Interstitial cells were affected almost exclusively, whereas apoptosis of cardiomyocytes was hardly detectable. However, the amount of apoptotic cells was too low to have a significant impact on organ function. Moreover, the anti-apoptotic Bcl-2 could be found in interstitial cells and seemed to have an apoptosis-protective effect in acute high-grade rejection.
Koch
A
A
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. Achim_Koch@med.uni-heidelberg.de
Roth
W
W
Steffek
T M
TM
Dengler
T J
TJ
Haass
M
M
Karck
M
M
Sack
F-U
FU
Schirmacher
P
P
Schnabel
P A
PA
D017209:Apoptosis; D016923:Cell Death; D002455:Cell Division; D006084:Graft Rejection / Q000473:pathology*; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D032383:Myocytes, Cardiac / Q000473:pathology; D016278:Ventricular Function, Right