Determinants of platelet kinetics: effects of pulmonary microembolism.
We examined the mechanisms of platelet uptake in the lungs after alpha-thrombin-induced pulmonary microembolism. Platelets labeled with 111In-oxine were reinfused into chronically prepared sheep. Pulmonary microembolism resulted in an increase in lung platelet radioactivity (95.5 +/- 15.3%; n = 4), which was followed by an exponential washout (half-life = 115 +/- 4 min). Platelet uptake in the lungs was more sustained after prior fibrinolytic inhibition with tranexamic acid (half-life = 178 +/- 11 min), although the initial increase was similar (90.7 +/- 9.6%; n = 7). Prior depletion of fibrinogen with ancrod (Arvin), blunted the initial increase in lung platelet uptake after alpha-thrombin challenge (31.7 +/- 11.3%, n = 5), indicating that the effect of thrombin was markedly dependent on fibrinogen. We examined the role of circulating granulocytes, since platelets may bind to subendothelial matrix exposed after granulocyte-mediated lung vascular injury. Maximal pulmonary platelet uptake after thrombin in granulocytopenic sheep was not different from control (71.7 +/- 14.4%; n = 4). The results indicate that pulmonary microembolism results in lung platelet sequestration. Platelet uptake is not dependent on granulocyte-mediated vascular injury but requires fibrin deposition and is sustained if fibrinolysis is inhibited.
McCandless
B K
BK
Department of Radiology, Albany Medical College, Union University, New York 12208.
Kaplan
J E
JE
Cooper
J A
JA
Malik
A B
AB
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001794:Blood Pressure; D002302:Cardiac Output; D005340:Fibrinogen / Q000502:physiology; D006207:Half-Life; D007205:Indium Radioisotopes; D007700:Kinetics; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D011651:Pulmonary Artery / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D012756:Sheep; D013154:Spleen / Q000473:pathology; D013917:Thrombin; D014148:Tranexamic Acid / Q000494:pharmacology; D014655:Vascular Resistance
D007205:Indium Radioisotopes; D014148:Tranexamic Acid; D005340:Fibrinogen; D013917:Thrombin