Masters Theses

Date of Award


Degree Type


Degree Name

Master of Science


Animal Science

Major Professor

Robert G. Schaub

Committee Members

Steve A. Kincaid, Robert E. Cartee, Robert L. Murphee


Thirty adult mixed-breed cats were used to assess the effects of indomethacin on collateral circulation inhibition following arterial thrombosis. Permanent ligation of the aorta at the iliac bifurcation is followed by rapid opening of pre-existent collateral vessels. If ligation is combined with aortic thrombosis, the collateral vessels will fail to develop. Both platelet activation and the presence of a hypercoagulable state have been implicated as causative factors in this collateral inhibition induced by thrombosis. Indomethacin, a platelet antagonist was tested for its ability to improve post-thrombolic collateralization.

Group 1 consisted of 11 cats which were subjected to aortic ligation, and received no treatment. Group 2 consisted of 9 cats with the aorta occluded by aortic ligation prior to the formation of an aortic thrombus. These animals received no drug therapy. The 10 cats in Group 3 received indomethacin (20 mg/kg i.v.) 1 hour prior to aortic occlusion. Group 3 cats were occluded by ligation plus aortic thrombosis, as in Group 2 animals.

Blood samples collected pre-occlusion and 3 hours post-occlusion were evaluated for hypercoagulability by OSPT, PTT, and protamine sulfate dilution tests. Pre- and post-occlusion blood samples were counted for platelets, and assessed for platelet activation by a transmission electron microscopic examination of platelet ultrastructure. Collateral blood flow was determined from aortograms taken 3 hours after aortic occlusion.

There were no significant differences in OSPT or PIT values among experimental groups (p ≤ 0.05). Fibrin monomer was moderately positive (1:20, 1:40) in only 2 cats from Group 1 and 2 cats from Group 2 after occlusion. Three animals from Group 2 had positive readings at 1:100 dilutions. Two of the indomethacin-treated cats (Group 3) had positive values of 1:40 and 1:80 after occlusion.

Post-occlusion platelet counts were significantly (p ≤ 0.05) higher in both indomethacin-treated (Group 3) and ligated (Group 1) cats than in thrombosed, non-treated cats (Group 2). Platelets from all 3 groups showed no signs of activation prior to surgery, but Group 2 and Group 3 cats had post-occlusion blood samples with activated platelets. These platelets exhibited vacuolization, degranulation, and signs of shape change. Group 1 cats had platelets which were normal in appearance in the post-occlusion blood samples.

During aortograms in Group 1 cats, contrast medium was visualized in the hindlimb vasculature within 1-2 seconds of injection. In Group 2 cats, there was no contrast medium visible beyond the area of occlusion after 7-8 seconds of injection time. Indomethacin-treated cats (Group 3) had aortograms in which contrast medium was seen in the hindlimb blood vessels within 1-2 seconds of initiation of injection.

These results indicate that hypercoagulability was not a significant factor in causing collateral inhibition following arterial thrombosis. It appears that platelet activation was critical to inhibiting collateral development. Activated platelets can release vasoactive substances which can induce vasospasm, as well as cause platelet aggregation. Platelet aggregates could physically block the vasculature and thus impair collateral development.

Previous studies (1-6) have implicated serotonin as a factor in thrombosis-mediated collateral inhibition. The release of serotonin and thromboxane A2 from activated platelets may be responsible for initiating vasoconstriction, as well as platelet aggregation, in the area of the thrombus. The vasoconstriction and the physical blockage of the collateral vessels by platelet aggregates may combine to impair post-thrombolic collateral circulation development.

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