The mechanism of thrombus formation in hyperlipidemia and atherosclerosis was studied using rabbits.
Attempts at artificial creation of arterial thrombus in control rabbits using Maekawa's technique of stenosing the femoral artery by ligature were not successful unless ellagic acid was administered by injection. Howevere, this thrombus formation could be prevented by oral administration of aspirin.
In rabbits with hyperlipidemia, mere creation of stenosis in the femoral artery resulted in a high percentage of thrombus formation with the prophylactic effect of aipirin being considerably decreased.
In rabbits with hyperlipidemia, both thromboxane (Tx) A2 biosynthesis in platelets and prostacyclin (PGI2) biosynthesis in the aorta were increased and these changes were noted at the level of cyclo-oxygenase in the arachidonic acid metabolic pathway. A diminished inhibitory effect of aspirin on TxA2 and PGI2 production was observed. In hyperlipidemia, although PGI2 biosynthesis was increased, mere creation of stenosis in the artery resulted in a high percentage of thrombus formation. Therefore, these results indicate that platelet hyperfunction is largely accountable for thrombus formation.
In rabbits with experimental atherosclerosis, TxA2 bsosynthesis of platelet was increased but PGI2 biosynthesis of aorta was decreaed.
These results indicate that thrombi are likely to be formed in hyperlipidemia, which may lead to atherosclerosis, and that such thrombus formation is due largely to platelet hyperfunction.