Donor Myocardial HIF‐1α Is an Independent Predictor of Cardiac Allograft Dysfunction: A 7‐Year Prospective, Exploratory Study

• Published in: American journal of transplantation Vol. 7; no. 8; pp. 2012 - 2019
• Main Authors: Aharinejad, S., Schäfer, R., Krenn, K., Zuckermann, A., Schneider, B., Neumann, F., Paulus, P., Wieselthaler, G., Wolner, E., Grimm, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2007; Blackwell
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart transplantation; HIF‐1α; marker; Medical sciences; Miscellaneous; primary graft dysfunction; Public health. Hygiene; Public health. Hygiene-occupational medicine; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Heart; Suboptimal donor; Human; Heart failure; Heart transplantation; Biological marker; Cardiovascular disease; Transplantation; HIF-1α; Homotransplantation; Prospective; Treatment; Heart disease; Surgery; marker; Myocardium; Graft; Transcription factor HIF1; Circulatory system; Graft primary dysfunction; Predictive factor; Public health; primary graft dysfunction
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2007.01875.x

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‐1α 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‐1α after aortic cross‐clamping in donors (78% sensitivity, 83% specificity) and at 10‐min reperfusion (85% sensitivity, 83% specificity) identified PGD. HIF‐1α 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.
Increased myocardial HIF‐1α mRNA expression after aortic cross‐clamping in donors is associated with primary cardiac allograft dysfunction.