Pronlonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell dysfunction in rat livers.
BACKGROUND
Although hypothermic machine perfusion (HMP) preservation has been shown to improve organ function and to expand the organ donor pool, problems still exist with the current HMP technology for liver preservation. The present study was conducted to investigate endothelial and hepatocellular functions following extended HMP (> r =24 hr) in rat liver model.


METHODS
Following 24-hour hypothermic HMP with University of Wisconsin (UW) solution or 24-hour simple cold storage (SCS), livers were reperfused with Krebs-Henseleit buffer solution at 37 degree C for 30 minutes. Hepatocyte damage and function were assessed by measuring lactate dehydrogenase (LDH) activity, bile production, and indocyanine green (ICG) extraction. Sinusoidal endothelial cell (SEC) function and permeability were determined by hyaluronic acid (HA) uptake and multiple indicator dilution (MID) method, respectively.


RESULTS
After 24-hour hypothermic preservation, HMP livers showed lower released LDH levels, higher bile flow rate, and greater hepatic ICG uptake compared with SCS livers. However, LDH levels became significantly higher in HMP than in SCS after 30 minutes of warm perfusion. The increased enzyme levels were accompanied by a significant increase in endothelial permeability to albumin and a decrease in hyaluronic acid uptake in HMP compared to SCS. Liver wet/dry weight ratio confirmed a greater edema in HMP livers than SCS livers.


CONCLUSIONS
These results suggest that 24-hour hypothermic HMP may help preservation of hepatocyte function, but endothelial cell dysfunction during the cold preservation may play a key role in hepatocyte dysfunction and parenchymal cell death upon reperfusion.
Xu
Hongzhi
H
Department of Biology, University of North Carolina, Charlotte, NC 28223, USA.
Lee
Charles Y
CY
Clemens
Mark G
MG
Zhang
Jian X
JX
D000241:Adenosine / Q000494:pharmacology; D000418:Albumins / Q000493:pharmacokinetics; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods*; D004487:Edema / Q000209:etiology; D004727:Endothelium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D022781:Hepatocytes; D006820:Hyaluronic Acid / Q000493:pharmacokinetics; D007328:Insulin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D009926:Organ Preservation / Q000009:adverse effects* / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D010477:Perfusion; D010539:Permeability; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014325:Tromethamine / Q000494:pharmacology
D000418:Albumins; D007328:Insulin; C074097:Krebs-Henseleit solution; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D014325:Tromethamine; D000493:Allopurinol; D006820:Hyaluronic Acid; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose