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Effect of thromboxane synthetase inhibition on canine autogenous vein grafts
Authors:E D Endean  J M Boorstein  P L Hees  J L Cronenwett
Institution:1. Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA;2. Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03756 USA;1. Royal Gwent Hospital, Newport, UK;2. Morriston Hospital, Swansea, UK;3. Frimley Park Hospital, Camberley, UK;4. Loyola University Hospital, Maywood, IL;5. University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands;6. Southmead Hospital, Bristol, UK;1. Department of Internal Medicine, Yale School of Medicine, New Haven, CT;2. Yale School of Medicine, New Haven, CT;3. Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Yale School of Medicine, New Haven, CT;4. Yale School of Public Health, New Haven, CT;5. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT;1. Division of Vascular and Endovascular Surgery, Department of Surgery, Duke University, Durham, NC;2. Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Abstract:This study examined the effect of an orally active thromboxane (TXA2) synthetase inhibitor (TSI) on the patency, TXA2 production, and platelet accumulation of reversed autogenous vein grafts. Ten dogs received TSI (U-63557A) 10 mg/kg po q8 hr for 6 weeks, beginning 24 hr prior to surgery, while 15 control dogs were untreated. One jugular vein was harvested and stored in 37 degrees C saline for 1 hr to induce mild endothelial injury (stored). Normal and stored jugular vein grafts (8 cm) were then implanted in opposite femoral arteries while 3-cm segments of the same veins were implanted in the carotid arteries. Femoral graft flow was restricted with a 5 Fr distal arterial stenosis and patency determined by arteriography at 1, 2, 4, and 6 weeks. Vein graft endothelial surface TXB2 production was measured by RIA at graft implantation and in carotid grafts harvested at 1 week. 111In-labeled platelets were given iv 24 hr prior to carotid graft harvest to determine graft-platelet deposition. TSI treatment improved early (1 week) femoral vein graft patency from 63 to 89% (P less than 0.05), a trend that persisted for 6 weeks. Warm saline storage reduced 1-week graft patency from 83 to 63% (P less than 0.05), a difference that decreased with time. TSI treatment resulted in a marked decrease in TXB2 production, but was not associated with decreased 111In-labeled platelet deposition in carotid vein grafts. Warm saline storage increased graft-platelet deposition which was predominant at the arterial anastomoses. TSI treatment may improve early vein graft patency during the transient period of endothelial injury.
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