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


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 (< or =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.
Koch
Achim
A
Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
Burgschweiger
Andreas
A
Herpel
Esther
E
Sack
Falk-Udo
FU
Schirmacher
Peter
P
Szabo
Gabor B
GB
Karck
Matthias
M
Schnabel
Philipp A
PA
D000368:Aged; D001706:Biopsy / Q000379:methods; D004699:Endocardium / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000201:enzymology*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015425:Myocardial Reperfusion / Q000009:adverse effects; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000209:etiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011237:Predictive Value of Tests
D052247:Nitric Oxide Synthase Type II