Sustained elevation of intracellular cyclic 3'-5' adenosine monophosphate
is necessary for preservation of platelet integrity during long-term
storage at 22 degrees C
AP Bode, S Holme, WA Heaton and MS Swanson
Departments of Pathology, East Carolina University School of Medicine,
Greenville, NC 27858.
Preservation of platelet integrity and responsiveness was examined in
platelet concentrates prepared in the presence of various formulations and
combinations of platelet-activation inhibitors affecting intracellular
levels of cyclic 3'-5' adenosine monophosphate (cAMP). Platelet
concentrates were prepared and stored in an artificial medium for two weeks
at 22 degrees C. Markers of metabolic activity (pH, lactate, pO2, pCO2 in
the medium), aggregation response, hypotonic shock response, and
glycoprotein Ib (GPIb) expression were assessed along with direct
measurements of cAMP in platelet pellets and thromboxane B2 (TxB2) in the
supernate. The platelet concentrates prepared with only adenylate-cyclase
stimulators (prostaglandin E-1 or forskolin) showed less maintenance of the
integrity and responsiveness 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.
Volume 83,
Issue 5,
pp. 1235-1243,
03/01/1994
Copyright © 1994 by The American Society of Hematology