Effects of thromboxane synthetase inhibition on patency and anastomotic hyperplasia of vascular grafts.
The efficacy of a thromboxane synthetase inhibitor (U-63,557A, Upjohn) in promoting early patency and inhibiting anastomotic intimal hyperplasia in ePTFE grafts was compared to that of acetylsalicylic acid (ASA) in a canine model. Animals were started on ASA 5 gr po qd (Group I, n = 12) or U-63,557A 10 mg/kg po bid (Group II, n = 12) 1 day before placement of bilateral 5-mm-i.d., 13- to 16.5-cm-long ePTFE aortoiliac grafts and continued on the medication for the 16-week study. Six dogs in each group received autologous endothelial cell-seeded grafts, while the other six received unseeded grafts. Patency was determined weekly by assessment of femoral pulses. At the conclusion of the study anastomotic intimal hyperplasia was measured on serial sections through the distal anastomosis using a computer-linked digitizer. In Group I the patencies of seeded and unseeded grafts were not significantly different, being 100 and 83%, respectively. Furthermore, luminal narrowing due to intimal hyperplasia was not significantly different being 9.1 +/- 7.6% (chi +/- SD) in seeded grafts and 8.8 +/- 8.1% in unseeded grafts. On the other hand, in Group II the seeded grafts had significantly improved patency when compared to the unseeded grafts (83% vs 33%, P less than 0.05) and less luminal narrowing (11.4 +/- 11.1% vs 21.9 +/- 19.5%, P less than 0.01). Although U-63,557A administration promoted patency of unseeded grafts compared to no antiplatelet medication (0% patency), it was significantly less effective than ASA in improving patency (P less than 0.05) and inhibiting luminal narrowing (P less than 0.01).
Graham
L M
LM
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109.
Brothers
T E
TE
Darvishian
D
D
Harrell
K A
KA
Vincent
C K
CK
Burkel
W E
WE
Stanley
J C
JC
D000714:Anastomosis, Surgical; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology / Q000637:transplantation; D011464:Epoprostenol / Q000096:biosynthesis; D006965:Hyperplasia; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014654:Vascular Patency / Q000187:drug effects*
D001572:Benzofurans; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C039936:furegrelate