Improved preservation solutions for organ storage: a dynamic study of hepatic metabolism.
BACKGROUND
Organ cold storage times may be extended by modifications to organ preservation solutions.


METHODS
Three preservation solutions were investigated for their ability to maintain viable hepatic bioenergetics in stored pig livers: modified University of Wisconsin (mUW); mUW+adenosine (1.34 g/L), and mUW+ iloprost (10(-8)mol/L), a prostacyclin analogue. Using human liver retrieval and storage techniques, pig livers were stored on ice for either 2 or 16 hr, after which phosphorus-31 spectra were collected every 2 min during the period of cold ischemia and hypothermic reperfusion (HtR). During HtR, metabolite concentration changes associated with phosphomonoesters, inorganic phosphate, gamma-nucleotide triphosphate (NTP), and beta-NTP were measured for all solutions.


RESULTS
After a 2-hr storage, beta-NTP regeneration in mUW+iloprost produced +57.7% (P<0.01) more beta-NTP, at a faster initial rate of +66.3% (P<0.001), compared with mUW, and mUW+adenosine regenerated +35.6% (P<0.05) more beta-NTP, compared with mUW. Storage for 16 hr did not slow the rates of regeneration, and the total NTP produced during the course of the experiment remained unchanged for the respective preservation solutions. Cessation of HtR invoked a net accumulation of nucleotide diphosphate, indicating differential kinetics of adenine nucleotide hydrolysis.


CONCLUSIONS
This large animal model study suggests significant improvements to human organ preservation solutions using prostacyclin analogues and adenosine with respect to hepatic bioenergetics.
Changani
K K
KK
Department of Surgery, Royal Free Hospital and Medical School, London, United Kingdom. kchangan@rpms.ac.uk
Fuller
B J
BJ
Bell
J D
JD
Taylor-Robinson
S D
SD
Moore
D P
DP
Davidson
B R
BR
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology / Q000592:standards; D000493:Allopurinol / Q000592:standards; D000818:Animals; D003080:Cold Temperature; D003451:Cryoprotective Agents / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000592:standards; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007328:Insulin / Q000592:standards; D008099:Liver; D016031:Liver Transplantation / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000592:standards*; D010755:Organophosphates; D011887:Raffinose / Q000592:standards; D015424:Reperfusion; D013552:Swine; D013997:Time Factors; D014969:Xanthine Oxidase / Q000502:physiology
D000227:Adenine Nucleotides; D003451:Cryoprotective Agents; D005609:Free Radicals; D007328:Insulin; D019188:Organ Preservation Solutions; D010755:Organophosphates; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D014969:Xanthine Oxidase; D005978:Glutathione; D016285:Iloprost; D000241:Adenosine; D011887:Raffinose