Prolonged cold storage using a new histidine-tryptophan-ketoglutarate-based preservation solution in isogeneic cardiac mouse grafts.
OBJECTIVE
The aim of this study was to evaluate a new histidine-tryptophan-ketoglutarate (HTK)-based cold preservation solution in comparison with traditional HTK solution in a mouse cardiac transplant model and to assess the impact of chloride ions and of iron chelators.


RESULTS
After 24 h cold ischaemia, traditional HTK-preserved hearts survived up to 13 days (4.4 ± 1.7 days; n = 8)). Hearts stored in the new solution without iron chelators (N46) showed significantly prolonged survival up to 2 months (N46: 11.9 ± 8.7 days; P < 0.01; n = 7) and with iron chelators (DesfLK) up to 3 months (N46 DesfLK: 12.7 ± 13.7 days; n = 6). Re-beating time was significantly shorter with the new solution (HTK: 14.5 ± 5.9 min, N46: 9.2 ± 2.7 min, N46 DesfLK: 7.1 ± 3.7 min; P < 0.01). The new solution showed significantly decreased release of creatine kinase (HTK: 25998 ± 8471 U/L, N46: 13829 ± 7679 U/L, N46 DesfLK: 3093 ± 597 U/L; P < 0.01 and n = 7 each) and lactate dehydrogenase (HTK: 5391 ± 1062 U/L, N46: 3428 ± 1890 U/L, P < 0.05; N46 DesfLK: 682 ± 344 U/L, P < 0.01) and decreased histological evidence of injury. A chloride-poor variant of the new solution showed inferior graft survival.


CONCLUSIONS
The new solution markedly attenuates myocardial injury and yields better graft survival than traditional HTK solution. The presence of chloride ions is crucial for heart preservation. Some protective effects are obviously caused by iron chelators.
Wu
Kun
K
Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Türk
Tobias R
TR
Rauen
Ursula
U
Su
Song
S
Feldkamp
Thorsten
T
de Groot
Herbert
H
Wiswedel
Ingrid
I
Baba
Hideo A
HA
Kribben
Andreas
A
Witzke
Oliver
O
D000818:Animals; D017209:Apoptosis; D002712:Chlorides / Q000032:analysis / Q000502:physiology; D050377:Cold Ischemia; D015925:Cryopreservation / Q000379:methods*; D028441:F2-Isoprostanes / Q000378:metabolism; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology; D006085:Graft Survival / Q000502:physiology*; D006321:Heart; D006639:Histidine / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D007656:Ketoglutaric Acids; D008297:Male; D008353:Mannitol / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000494:pharmacology*; D011189:Potassium Chloride / Q000737:chemistry / Q000494:pharmacology; D011343:Procaine / Q000737:chemistry / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology
C039984:Bretschneider cardioplegic solution; D002712:Chlorides; D028441:F2-Isoprostanes; D007502:Iron Chelating Agents; D007656:Ketoglutaric Acids; D019188:Organ Preservation Solutions; D008353:Mannitol; D006639:Histidine; D011343:Procaine; D011189:Potassium Chloride; D014364:Tryptophan; D005947:Glucose