Simultaneous 51CR AND 14C-Serotonin Platelet Survival Measurements

In vivo platelet reactions resulting in platelet utilization or release of constituents without platelet destruction have been studied in baboons by measuring isotopic disappearance of doubly labeled platelets using 51Cr as the cytoplasmic label to detect destruction and 14C-serotonin as a granular |abel to detect release. In 25 normal animals, the 14C-serotonin platelet survival (14C-SPS) was 6.0 days ± 0.2 compared with a Cr platelet survival (51Cr-PS) of 5.5 days ± 0.2, suggesting about 10% reutilization of the 14C label. Platelet labeling in vivo with 51C-serotonin showed that only 13% ± 2% of the injected activity became platelet bound; the remainder was cleared from the plasma within three hours. The platelets labeled in vivo survived normally (6.0 days ± 0.4). These results indicale that in vivo reutilization of serotonin is not extensive and that the process of labeling platelets with Cr in vitro does not appreciably shorten their survival in vivo. In other studies, animals with doubly labeled platelets received intravenous infusions of thrombin, ionophore R02-2985, arachidonic acid, ADP, collagen, plasmin, streptokinase, endotoxin, bovine factor VIII, and air bubbles. Thrombin or collagen infusions produced rapid, equivalent disappearance of both labels that correlated closely with decreases in platelet counts indicating that platelet destruction is not associated with reuptake of released C-serotonin by ambient circulating platelets. In contrast the infusions of R1I2-2985, plasmin or some studies with endotoxin induced selective disappearance of 51C-serotonin while 51Cr-PS was normal, reflecting platelet release in vivo without platelet destruction. With ADP, arachidonic acid, streptokinase and air bubbles platelets disappeared from the circulation transiently without loss of either label indicating transient platelet sequestration. We conclude that doubly labeled platelet survival studies are useful in characterizing platelet reactions and their pharmacologic alterations in vivo.