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By H. James Day M.D. (auth.), H. James Day M.D., Basil A. Molony M.D., Edward E. Nishizawa Ph.D., Ronald H. Rynbrandt Ph.D. (eds.)

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Sample text

Cazenave replied that although he has no direct evidence, possibly the smooth muscle cells are the source for PGI2 synthesis. Dr. Salzman cited the work of MacIntyre, Pearson, and Gordon 1 which indicated that in culture, only endothelial cells produced PGI2. Dr. Mustard said that while endothelial cells do make PGI2, there is no evidence that smooth muscle cells do not make it, and he cited some animal studies that suggest they do. If a hole is made with a needle in the jugular vein of a thrombocytopenic rabbit, the bleeding persists but it can be stopped by 1) replacing platelets in the rabbit, 2) treating the vessel wall with hydrocortisone or methylprednisolone, or 3) treating the vessel wall with aspirin or indomethacin.

36 TABLE 2. EFFECT OF TREATMENTS OF PLATELET SURFACE ON PLATELET ADHERENCE Treatments which reduce adherence Thrombin Treatment which has no effect Removal of sialic acid Plasmin Trypsin Chymotrypsin ADP lets, it was possible to treat the platelets in various ways during the isolation procedure and then resuspend them in the final suspending medium. Platelets can be treated with thrombin and recovered as individual platelets that have lost most of their granule contents (50). These "degranulated" platelets show a diminished ability to adhere to collagen-coated surfaces and to subendothelium.

Similar results were obtained when these drugs were used to inhibit platelet adherence to subendothelium. These results show that measuring platelet adherence to collagencoated surfaces can be used as a screening test in attempts to determine how effectively drugs inhibit platelet interaction with the vessel wall at sites of vessel injury and thereby how effective they may be as inhibitors of thrombosis. It has recently been shown that aspirin and sulfinpyrazone do not inhibit platelet adherence in vivo to rabbit aortas injured with a balloon catheter; in contrast, dipyridamole reduced adherence to half of the control values (Groves HM, Kinlough-Rathbone RL, Richardson M, Mustard JF, unpublished observations).

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