Nitric oxide infusion alleviates cellular activation during preparation, leukofiltration and storage of platelets.
Nitric oxide (NO) is a reversible inhibitor of platelet activation that generates S-nitrosylated compounds in plasma. Since platelets are activated during processing to platelet concentrates and storage, NO is anticipated to dampen the rate of lesion development. Platelet-rich plasma (PRP) was separated into aliquots that were unfiltered, filtered to remove leukocytes, or treated with NO or nitrite before filtration. Platelets were resuspended and stored up to four days at 22 degrees C. Samples removed were measured for S-nitrosylation of plasma, P-Selectin release, complement activation, and cGMP levels. Direct infusion of a NO solution (authentic NO) to PRP before filtration decreased adherence of platelets and improved yields. An infusion rate resulting in 1/1000 dilution of a saturated NO solution was optimal. C3a formation and soluble P-Selectin released from NO-treated-filtered platelets were about half that in unfiltered and filtered controls after four days (p<0.05 by Student-Newman-Keuls method after ANOVA for repeated measures). Plasma isolated from NO-treated PRP combined with untreated platelets protected the latter to a similar extent. Increases in S-nitrosylated compounds in PRPs were correlated with NO effects on platelet recovery and storage. Sodium nitrite failed to inhibit platelet activation and cyclic GMP levels were significantly increased in NO-treated cells. Results indicate that NO inhibited platelet activation associated with processing and storage and suggest that slow release of NO from S-nitrosylated plasma components afforded long-term protection. The infusion of authentic NO into PRPs is potentially an efficacious method for generating anti-platelet compounds to inhibit storage lesions.
Wong
Kenneth
K
Canadian Blood Services, Calgary Centre, 737-13 Ave. S.W., AB T2R 1J1 Calgary, Canada. kwong@ucalgary.ca
Li
Xuebin
X
D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D001793:Blood Preservation / Q000379:methods*; D003167:Complement Activation; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D008163:Luminescent Measurements; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D012977:Sodium Nitrite / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D019007:P-Selectin; D009569:Nitric Oxide; D006152:Cyclic GMP; D012977:Sodium Nitrite