Factors contributing to increased vascular fibrinolytic activity in mongrel dogs.
BACKGROUND
Numerous investigators have observed that pulmonary emboli are rapidly lysed in a canine model system. This study was undertaken to delineate the unique mechanism that accounts for the rapid dissolution of pulmonary emboli in mongrel dogs.


RESULTS
Canine plasminogen activator (PA) activity (2.6 +/- 1.1 IU/mL acidified platelet-poor plasma [PPP], < 0.3 IU/mL acidified whole blood serum [WBS], mean +/- SD; n = 6) and PA inhibitor activity (6.1 +/- 2.6 U/mL PPP, 35.4 +/- 7.8 U/mL WBS; n = 6) were determined in standard plasminogen-based chromogenic assays. Analysis of canine PPP, WBS, platelet lysates, and primary canine endothelial cell (EC) cultures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography revealed a plasminogen-dependent lytic zone at 45-kd relative molecular mass that was shown to be related to urokinase-type PA (u-PA) by its selective inhibition through amiloride. Analysis of canine platelets on standard 125I fibrin plate assays revealed a net fibrinolytic activity. In a clot lysis assay system, canine platelets were able to stimulate fibrinolysis when layered on the outside of fibrin clots containing autologous PPP. Moreover, net fibrinolytic activity of primary canine pulmonary artery endothelial cells was higher than the activities expressed by canine aortic or carotid artery endothelial cells.


CONCLUSIONS
Rapid lysis of pulmonary emboli in mongrel dogs appears to be a result of 1) the high u-PA activity in canine PPP and 2) the predominant association of u-PA activity with canine platelets and canine pulmonary artery endothelial cells.
University of California, San Diego.
I M
IM
Lang
J J
JJ
Marsh
R G
RG
Konopka
M A
MA
Olman
B R
BR
Binder
K M
KM
Moser
R R
RR
Schleef
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D011655:Pulmonary Embolism / Q000097:blood*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator