University of Wisconsin (UW) Solution
The multiple factors influencing the effectiveness of preservation were analysed by Southard et al., who produced a solution (UW) containing impermeants (raffinose, lactobionate), buffers (phosphate), free radical inhibitors and scavengers (glutathione, allopurinol), energy precursors (adenosine), vasoactive agents and hormones (steroids, insulin), and a colloid (hydroxyethyl starch). This complex solution was markedly more effective than other solutions (Collins', citrate, phosphate buffered sucrose) used for liver and pancreas preservation, and also for kidney and heart grafts. It was suitable both for cold-flush storage, and for continuous perfusion. Not all its components are equally important: hydroxyethyl starch can safely be omitted for cold flushing and simple hypothermic storage. High potassium levels are undesirable on several grounds, and reversing Na:K ratios does not significantly lower efficacy. Other additives, such as the buffer histidine, can improve preservation; the polysaccharide raffinose can be replaced by sucrose. Lactobionate is probably the most effective and most important component of UW solution. Gluconate (molecular weight 195 Da) appears slightly less effective as an alternative impermeant. Other adjuvants shown to be helpful include raffinose, glutathione, allopurinol, and adenosine. Steroids, insulin, and hydroxyethyl starch (HES) are of minor significance. Modified HES-free UW-derived solutions based on high concentrations of sodium lactobionate can give results similar or equal to the original UW solution.
Extension of experimental preservation by simple cold storage after flushing with modified UW solutions has been achieved for kidneys to 5 days, pancreas to 48 h, liver to 36 to 48 h, and for heart and lung towards 12 h. Recent clinical trials have confirmed the effectiveness of lactobionate-based UW solutions in preservation of kidney, liver, and pancreas; improved heart preservation for transplantation with UW flushing and storage has been demonstrated over standard cardioplegic solutions. Solutions with high concentrations of histidine, tryptophane, and &agr;-ketoglutarate (Bretschneider-HTK) have also given improved organ preservation.
Other agents shown to be helpful additives to flushing solutions (and which hold promise for further extension of preservation times) include other energy sources and buffers, calcium channel blockers (verapamil, diltiazem, trifluoperazine), and stable prostacyclin analogues.
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