Oxygen-charged HTK-F6H8 emulsion reduces ischemia-reperfusion injury in kidneys from brain-dead pigs.
BACKGROUND
Prolonged cold ischemia is frequently associated with a greater risk of delayed graft function and enhanced graft failure. We hypothesized that media, combining a high oxygen-dissolving capacity with specific qualities of organ preservation solutions, would be more efficient in reducing immediate ischemia-reperfusion injury from organs stored long term compared with standard preservation media.


METHODS
Kidneys retrieved from brain-dead pigs were flushed using either cold histidine-tryptophan-ketoglutarate (HTK) or oxygen-precharged emulsion composed of 75% HTK and 25% perfluorohexyloctane. After 18 h of cold ischemia the kidneys were transplanted into allogeneic recipients and assessed for adenosine triphosphate content, morphology, and expression of genes related to hypoxia, environmental stress, inflammation, and apoptosis.


RESULTS
Compared with HTK-flushed kidneys, organs preserved using oxygen-precharged HTK-perfluorohexyloctane emulsion had increased elevated adenosine triphosphate content and a significantly lower gene expression of hypoxia inducible factor-1α, vascular endothelial growth factor, interleukin-1α, tumor necrosis factor-α, interferon-α, JNK-1, p38, cytochrome-c, Bax, caspase-8, and caspase-3 at all time points assessed. In contrast, the mRNA expression of Bcl-2 was significantly increased.


CONCLUSIONS
The present study has demonstrated that in brain-dead pigs the perfusion of kidneys with oxygen-precharged HTK-perfluorohexyloctane emulsion results in significantly reduced inflammation, hypoxic injury, and apoptosis and cellular integrity and energy content are well maintained. Histologic examination revealed less tubular, vascular, and glomerular changes in the emulsion-perfused tissue compared with the HTK-perfused counterparts. The concept of perfusing organs with oxygen-precharged emulsion based on organ preservation media represents an efficient alternative for improved organ preservation.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. sana.asif@igp.uu.se
Sana
S
Asif
Amir
A
Sedigh
Johan
J
Nordström
Heide
H
Brandhorst
Carl
C
Jorns
Tomas
T
Lorant
Erik
E
Larsson
Peetra U
PU
Magnusson
Greg
G
Nowak
Sonja
S
Theisinger
Simone
S
Hoeger
Lars
L
Wennberg
Olle
O
Korsgren
Daniel
D
Brandhorst
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001926:Brain Death; D016207:Cytokines / Q000235:genetics; D004655:Emulsions; D005260:Female; D005947:Glucose / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D010100:Oxygen / Q000494:pharmacology*; D011189:Potassium Chloride / Q000627:therapeutic use; D011343:Procaine / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
C039984:Bretschneider cardioplegic solution; D016207:Cytokines; D004655:Emulsions; D012333:RNA, Messenger; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen