Mitochondrial ischemia-reperfusion injury of the transplanted rat heart: improved protection by preservation versus cardioplegic solutions.
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.
Schneeberger
Stefan
S
Daniel Swarovski Research Laboratory, Department of General and Transplant Surgery, Medical University Innsbruck, Innsbruck, Austria.
Kuznetsov
Andrey V
AV
Seiler
Rüdiger
R
Renz
Oliver
O
Meusburger
Hugo
H
Mark
Walter
W
Brandacher
Gerald
G
Margreiter
Raimund
R
Gnaiger
Erich
E
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D016027:Heart Transplantation; D007328:Insulin / Q000494:pharmacology; D007511:Ischemia; D008297:Male; D008928:Mitochondria / Q000473:pathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D019188:Organ Preservation Solutions / Q000494:pharmacology; D010539:Permeability; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology*
D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D002950:Citrate (si)-Synthase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose