Kinetics of pulmonary platelet deposition and clearance during thrombin-induced microembolism in rabbits.
Using 111In-labeled autologous platelets, we studied the kinetics of pulmonary platelet deposition and clearance in relation to hemodynamic and structural events during thrombin-induced pulmonary microembolism in rabbits. Autologous platelets were radiolabeled and returned to animals prior to infusion of thrombin (100 units/kg over 15 min) (n = 20) or saline (n = 6). All animals were pretreated with tranexamic acid, an inhibitor of fibrinolysis. Thrombin-treated animals manifested progressive increases in mean pulmonary platelet activity, reaching a maximum of 38% above baseline (p less than .0001), whereas no change was observed in saline-treated controls. Animals that died during, or immediately following, thrombin infusion manifested significantly greater increases in pulmonary platelet uptake (mean 1.55 +/- 0.47 times baseline), compared to surviving animals (1.14 +/- 0.16; p less than .05 survivors vs. nonsurvivors). In surviving animals, following cessation of thrombin, pulmonary platelet activity cleared gradually, with a half-time of approximately 12 min. Thrombin reduced circulating platelet counts (p less than .001), increased mean pulmonary artery pressure (13 +/- 3 mm Hg to 18 +/- 6 mm Hg; p less than .0001), and reduced mean systemic arterial pressure (55 +/- 10 mm Hg to 44 +/- 7 mm Hg; p less than .001). The time courses of these events approximated that of thrombin-induced pulmonary platelet uptake. Furthermore, the increase in pulmonary artery pressure occurred predominantly in the group of animals in which the increase in pulmonary radiolabeled platelet activity exceeded the median value of 20%. Postmortem histology showed extensive pulmonary thrombus extending from small arterial to capillary levels in animals that died during, or immediately following, thrombin infusion, but not in surviving animals. Our findings suggest that platelet aggregation plays an important role in the pathogenesis of hemodynamic change following thrombin-induced pulmonary embolization.
Konstam
M A
MA
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
Brockway
B A
BA
Aronovitz
M J
MJ
Ramberg
K
K
Palabrica
T M
TM
Otradovec
C L
CL
Cooper
A
A
Hill
N
N
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D011817:Rabbits; D011877:Radionuclide Imaging; D013917:Thrombin
D013917:Thrombin