Cold ischemia contributes to the development of chronic rejection and mitochondrial injury after cardiac transplantation

Stefan Schneeberger, Albert Amberger, Julia Mandl, Theresa Hautz, Oliver Renz, Peter Obrist, Hugo Meusburger, Gerald Brandacher, Walter Mark, Daniela Strobl, Jakob Troppmair, Johann Pratschke, Raimund Margreiter, Andrey V. Kuznetsov

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1282-1292
Number of pages11
JournalTransplant International
Volume23
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • cardiac transplantation
  • chronic rejection
  • cold ischemia
  • mitochondrial function
  • respirometry

ASJC Scopus subject areas

  • Transplantation

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