A Direct Relationship between Adenosine Triphosphate-level and in vivo Viability of Erythrocytes

The Mechanism of Action of Adenine in Red Cell Preservation*

“…This continued slow incorporation of adenine into adenine nucleotides, rather than any inhibitory effect of adenine on adenine nucleotide breakdown, appeared responsible for the slower decline of total adenine nucleotides with adenine supplementation (Table III). Thus, between days 16 and 44 of storage, the rate of hypoxanthine accumulation was similar in all samples (column 3), and the amount of adenine that disappeared (column 2) approximated the difference in adenine nucleotide decline between samples stored with and without adenine (column 1). There was no breakdown of adenine nucleotides into adenine since the specific radioactivity of adenine remained constant throughout the storage period.…”

“…Finally, incubation of human red cells with adenosine-8-C14 failed to produce more labeling in the adenine portion of ATP than did inosine-8-C14 (22). Nevertheless, red cell viability is better maintained with adenosine than with inosine (3), and adenosine appears to be more effective than inosine, inosine plus adenine, or adenine alone in maintaining and regenerating ATP in stored or nucleotide-depleted cells (2,(31)(32)(33)(34)(35)(36)(37)(38). Since adenosine, through deamination, may raise pH and would thus be expected to maintain hexokinase activity (39), possibly some of the aforementioned effects of adenosine on ATP maintenance and viability may be explained by this means.…”

“…Finally, we must emphasize that although higher ATP or adenine nucleotide levels are associated with better post-transfusion survival under these conditions of storage (3)(4)(5)(6)57), it is premature to speculate regarding a specific level of adenine nucleotides required to give a certain per cent post-transfusion survival. There are several reasons for this: 1) factors other than the adenine nucleotide level may be of critical importance, especially if the conditions of storage are altered; 2) there remains too much interlaboratory variation both in the measurement of adenine nucleotides and of post-tranfusion survival; and, perhaps most important, 3) adenine nucleotide levels (or any other in vitro measurement) obtained after a period of storage reflect a composite both of cells that are destined for very rapid removal from the circulation and of those that survive normally or nearly so.…”

“…370 C with both adenine and inosine, regeneration of ATP and restoration of post-transfusion viability took place (1)(2)(3). ATP regeneration did not occur when the incubation medium contained either adenine or inosine alone.…”

“…ATP regeneration did not occur when the incubation medium contained either adenine or inosine alone. Moreover, supplementation of the ACD preservative with both adenine and inosine at the beginning of storage resulted in better maintenance of ATP and posttransfusion viability than in samples stored with inosine alone or not supplemented at all (3)(4)(5).…”