TY - JOUR
T1 - Cold ischemia contributes to the development of chronic rejection and mitochondrial injury after cardiac transplantation
AU - Schneeberger, Stefan
AU - Amberger, Albert
AU - Mandl, Julia
AU - Hautz, Theresa
AU - Renz, Oliver
AU - Obrist, Peter
AU - Meusburger, Hugo
AU - Brandacher, Gerald
AU - Mark, Walter
AU - Strobl, Daniela
AU - Troppmair, Jakob
AU - Pratschke, Johann
AU - Margreiter, Raimund
AU - Kuznetsov, Andrey V.
PY - 2010/12
Y1 - 2010/12
N2 - Chronic rejection (CR) remains an unsolved hurdle for long-term heart transplant survival. The effect of cold ischemia (CI) on progression of CR and the mechanisms resulting in functional deficit were investigated by studying gene expression, mitochondrial function, and enzymatic activity. Allogeneic (Lew→F344) and syngeneic (Lew→Lew) heart transplantations were performed with or without 10 h of CI. After evaluation of myocardial contraction, hearts were excised at 2, 10, 40, and 60 days for investigation of vasculopathy, gene expression, enzymatic activities, and mitochondrial respiration. Gene expression studies identified a gene cluster coding for subunits of the mitochondrial electron transport chain regulated in response to CI and CR. Myocardial performance, mitochondrial function, and mitochondrial marker enzyme activities declined in all allografts with time after transplantation. These declines were more rapid and severe in CI allografts (CR-CI) and correlated well with progression of vasculopathy and fibrosis. Mitochondria related gene expression and mitochondrial function are substantially compromised with the progression of CR and show that CI impacts on progression, gene profile, and mitochondrial function of CR. Monitoring mitochondrial function and enzyme activity might allow for earlier detection of CR and cardiac allograft dysfunction.
AB - Chronic rejection (CR) remains an unsolved hurdle for long-term heart transplant survival. The effect of cold ischemia (CI) on progression of CR and the mechanisms resulting in functional deficit were investigated by studying gene expression, mitochondrial function, and enzymatic activity. Allogeneic (Lew→F344) and syngeneic (Lew→Lew) heart transplantations were performed with or without 10 h of CI. After evaluation of myocardial contraction, hearts were excised at 2, 10, 40, and 60 days for investigation of vasculopathy, gene expression, enzymatic activities, and mitochondrial respiration. Gene expression studies identified a gene cluster coding for subunits of the mitochondrial electron transport chain regulated in response to CI and CR. Myocardial performance, mitochondrial function, and mitochondrial marker enzyme activities declined in all allografts with time after transplantation. These declines were more rapid and severe in CI allografts (CR-CI) and correlated well with progression of vasculopathy and fibrosis. Mitochondria related gene expression and mitochondrial function are substantially compromised with the progression of CR and show that CI impacts on progression, gene profile, and mitochondrial function of CR. Monitoring mitochondrial function and enzyme activity might allow for earlier detection of CR and cardiac allograft dysfunction.
KW - cardiac transplantation
KW - chronic rejection
KW - cold ischemia
KW - mitochondrial function
KW - respirometry
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UR - http://www.scopus.com/inward/citedby.url?scp=78649254011&partnerID=8YFLogxK
U2 - 10.1111/j.1432-2277.2010.01126.x
DO - 10.1111/j.1432-2277.2010.01126.x
M3 - Article
C2 - 20561305
AN - SCOPUS:78649254011
SN - 0934-0874
VL - 23
SP - 1282
EP - 1292
JO - Transplant International
JF - Transplant International
IS - 12
ER -