Improved preservation solutions for organ storage - A dynamic study of hepatic metabolism

Background. Organ cold storage times may be extended by modifications to or gan preservation solutions, Methods. Three preservation solutions were investigated for their ability t o maintain viable hepatic bioenergetics in stored pig livers: modified Univ ersity 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 whic h phosphorus-31 spectra were collected every 2 min during the period of col d ischemia and hypothermic reperfusion (HtR), During HtR, metabolite concen tration changes associated with phosphomonoesters, inorganic phosphate, gam ma-nucleotide triphosphate (NTP), and beta-NTP were measured for all soluti ons. Results. After a 2-hr storage, beta-NTP regeneration in mUW+iloprost produc ed +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 exper iment remained unchanged for the respective preservation solutions. Cessati on of HtR invoked a net accumulation of nucleotide diphosphate, indicating differential kinetics of adenine nucleotide hydrolysis, Conclusion. This large animal model study suggests significant improvements to human organ preservation solutions using prostacyclin analogues and ade nosine with respect to hepatic bioenergetics.