Sustained Elevation of Intracellular Cyclic 3’-5’ Adenosine MonophosphateIs Necessary for Preservation of Platelet Integrity During Long-Term Storage at 22°C

Abstract

AbstractPreservation of platelet integrity and responsiveness was sponsiveness markers and greater loss of GPIb than con-examined in platelet concentrates prepared in the pres- centrates prepared with phosphodiesterase inhibitors (the ence of various formulations and combinations of platelet- ophylline or caffeine) or combinations with the above. activation inhibitors affecting intracellular levels of cyclic These results were correlated with the ability of these 3’-5’ adenosine monophosphate (cAMP). Platelet concen- compounds to sustain elevation of cAMP above basal level trates were prepared and stored in an artificial medium for during the entire extended-storage period. The strong cor-two weeks at 22°C. Markers of metabolic activity (pH, lac- relation (rs = - 0.67) between elevation of cAMP levels tate, pO2,pCO2 in the medium), aggregation response, hy- and suppression of TxB2 production suggests that the potonic shock response, and glycoprotein lb (GPIb) expres- phosphodiesterase inhibitors provided better protectionsion were assessed along with direct measurements of than stimulators of adenylate cyclase alone through a re-cAMP in platelet pellets and thromboxane B2 (TxB2) in the duction in platelet activation and its deleterious effects on supemate. The platelet concentrates prepared with only preservation of platelets during storage. adenylate-cyclase stimulators (prostaglandin E-1 or forskolin) showed less maintenance of the integrity and re- sponsiveness markers and greater loss of GPIb than concentrates prepared with phosphodiesterase inhibitors (theophylline or caffeine) or combinations with the above. These results were correlated with the ability of these compounds to sustain elevation of cAMP above basal level during the entire extended-storage period. The strong correlation (rs = −0.67) between elevation of cAMP levels and suppression of TxB2 production suggests that the phosphodiesterase inhibitors provided better protection than stimulators of adenylate cyclase alone through a reduction in platelet activation and its deleterious effects on preservation of platelets during storage.