Donor myocardial HIF-1alpha is an independent predictor of cardiac allograft dysfunction: a 7-year prospective, exploratory study.
Knowledge on interplay between the cardiac molecular response to transplantation-induced stress and primary graft dysfunction (PGD) is limited. A cDNA array identified HIF-1, EGR-1, NAB-2, VEGF-A and uPA as mediators of cardiac tissue response to transplantation-induced stress. mRNA expression of these molecules was measured in left ventricular biopsies from 200 donors before and after aortic cross-clamping and at 10-, 30- and 60-min reperfusion by real-time RT-PCR. HIF-1alpha expression at two time points was significantly associated with PGD, as shown by univariate analysis, receiver operating characteristic curve and multivariate logistic regression. At a cut-off level of 200 arbitrary units, HIF-1alpha after aortic cross-clamping in donors (78% sensitivity, 83% specificity) and at 10-min reperfusion (85% sensitivity, 83% specificity) identified PGD. HIF-1alpha demonstrates the potential to be a predictive marker for PGD; however, as multiple factors were tested at different time points, prospective evaluation is clearly necessary to confirm this observation.
Aharinejad
S
S
Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria. seyedhossein.aharinejad@meduniwien.ac.at
Schäfer
R
R
Krenn
K
K
Zuckermann
A
A
Schneider
B
B
Neumann
F
F
Paulus
P
P
Wieselthaler
G
G
Wolner
E
E
Grimm
M
M
D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D017548:Echocardiography, Transesophageal; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006333:Heart Failure / Q000601:surgery; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics*; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism
D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger