Mitochondrial ischemia-reperfusion injury of the transplanted rat heart: Improved protection by preservation versus cardioplegic solutions

Stefan Schneeberger, Andrey V. Kuznetsov, Rüdiger Seiler, Oliver Renz, Hugo Meusburger, Walter Mark, Gerald Brandacher, Raimund Margreiter, Erich Gnaiger

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Cold ischemia time and preservation of organs are limited by I/R injury leading to primary nonfunction of the graft. In a rat heart transplant model, we compared cardioplegic St Thomas (ST) to histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin preservation solutions in terms of contractile function, and mitochondrial respiratory and enzymatic defects after prolonged cold ischemia and reperfusion. Contractile function was scored after transplantation and 24 h of reperfusion. Mitochondrial function was investigated by high-resolution respirometry of permeabilized myocardial fibers. Graft performance in terms of contractile function declined with the duration of cold storage. Recovery was significantly improved after 10 h of cold storage in HTK compared with ST (cardiac scores, 3.3 ± 0.5 and 1.8 ± 0.8, respectively). Tissue lactate dehydrogenase was better preserved in HTK than ST. Increase of tissue water content (edema) was less pronounced in HTK than ST (3.33 ± 0.14 and 3.73 ± 0.21 mg/mg dry weight, respectively). Similar cardiac scores (2.6 ± 0.9 and 2.9 ± 1.2, respectively) and mitochondrial respiratory parameters were obtained after preservation in HTK and University of Wisconsin. Decline in contractile function of individual grafts correlated well with loss of mitochondrial respiratory capacity, whereas citrate synthase activity remained largely preserved, indicating specific damage of respiratory complexes. Our data provide evidence for the superiority of preservation solutions versus a cardioplegic solution for prolonged cold storage of the heart. The correlation of graft performance and mitochondrial function indicates the potential of high-resolution respirometry for quantitative assessment of myocardial injury upon cold I/R, providing a basis for diagnostic approaches and evaluation of improved preservation solutions for heart transplantation.

Original languageEnglish (US)
Pages (from-to)365-371
Number of pages7
JournalShock
Volume30
Issue number4
DOIs
StatePublished - Oct 2008
Externally publishedYes

Keywords

  • Cardiac function
  • Heart preservation
  • Heart transplantation
  • Mitochondrial function
  • Permeabilized fibers

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint

Dive into the research topics of 'Mitochondrial ischemia-reperfusion injury of the transplanted rat heart: Improved protection by preservation versus cardioplegic solutions'. Together they form a unique fingerprint.

Cite this