Blood glutathione as a marker of cardiac allograft vasculopathy in heart transplant recipients.
BACKGROUND
Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV.


METHODS
Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis.


RESULTS
CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008).


CONCLUSIONS
In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.
De Chiara
Benedetta
B
CNR Clinical Physiology Institute, Section of Milan, Milan, Italy.
Bigi
Riccardo
R
Campolo
Jonica
J
Parolini
Marina
M
Turazza
Fabio
F
Masciocco
Gabriella
G
Frigerio
Maria
M
Fiorentini
Cesare
C
Parodi
Oberdan
O
D015415:Biomarkers / Q000097:blood; D005978:Glutathione / Q000097:blood*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods*; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000097:blood* / Q000209:etiology
D015415:Biomarkers; D005978:Glutathione