Inhibition of Experimental Venous Thrombosis

Abstract

The injection of glycerin or a sclerosing agent like Sotradecol (sodium tetradecyl sulfate) into the marginal ear vein of the rabbit produces immediate thrombosis of the vein. We have attempted to modify the reaction in and about the vein by means of Butazolidin3 (phenylbutazone), a drug which had displayed anti-inflammatory action of a high order under diverse clinical conditions (1-4) and, more particularly, in the treatment of superficial thrombophlebitis (5). MATERIAL AND METHODSThe irritant, 0.2 ml, was injected with a minimum of trauma into the marginal vein at the tip of the ear of adult female rabbits weighing approximately 2 kg.There were five groups of seven animals each. Groups 1 and 2 were &dquo;protected&dquo; 24 hr prior to thrombosis of the ear vein and up to 48 hr afterward by the intramuscular injection of 50 mg per kilogram body weight of phenylbutazone in lidocaine into the posterior quadrant of each animal every 6 hr. The total dosage therefore ranged from 400 to 1200 mg.Groups 3 and 4 were &dquo;protected&dquo; in a similar manner immediately after inducing thrombosis of the ear vein. The maximum total dosage used in these groups was from 400 to 800 mg.Group 5 was a control group of animals in uThich the venous thrombosis was permitted to follow its normal course.Segments of ears transecting the thrombosed vein were cut from the successive groups of animals, first at 3 hr after the induced thrombosis and at 6, 9, 12, 24, and 48 hr later. These sections were taken from the middle of the thrombosed vessel and fixed immediately. RESULTSHistologically ( fig. 1), a firm fibrin and red-cell clot was present after 3 hr both in &dquo;protected&dquo; and in control rabbits. There was no reaction in the perivascular tissues.At 6 hr, differences first became apparent. In the &dquo;protected&dquo; animal there was a healthy fibrin clot with very few leukocytes and no escape into the stroma. In the control, or &dquo;unprotected,&dquo; animal there was peripheral positioning of leukocytes in the fresh fibrin clot, and escape into the perivascular stroma was beginning.