TY - JOUR
T1 - Mitochondrial ischemia-reperfusion injury of the transplanted rat heart
T2 - Improved protection by preservation versus cardioplegic solutions
AU - Schneeberger, Stefan
AU - Kuznetsov, Andrey V.
AU - Seiler, Rüdiger
AU - Renz, Oliver
AU - Meusburger, Hugo
AU - Mark, Walter
AU - Brandacher, Gerald
AU - Margreiter, Raimund
AU - Gnaiger, Erich
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
KW - Cardiac function
KW - Heart preservation
KW - Heart transplantation
KW - Mitochondrial function
KW - Permeabilized fibers
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U2 - 10.1097/SHK.0b013e318164f09f
DO - 10.1097/SHK.0b013e318164f09f
M3 - Article
C2 - 18317412
AN - SCOPUS:54049123269
SN - 1073-2322
VL - 30
SP - 365
EP - 371
JO - Shock
JF - Shock
IS - 4
ER -