Biochemical (functional) adaptation of "arterialized" vein grafts

Abstract

Canine venous autografts and allografts were interposed in the femoral and carotid arterial positions in 29 dogs; grafts were harvested at three postoperative intervals (1-2 weeks, 4-6 weeks, and 8-10 weeks) for light and scanning electron (SEM) microscopy and lumenal surface prostacyclin (PGI2) production. Normal veins and arteries were used as controls. Radioimmunoassay for tritiated 6-k-PGF1 alpha, the stable metabolite of PGI2, was performed using a flow surface template incubation chamber during basal and arachidonic acid stimulated conditions. Using SEM, the autografts revealed normal endothelial cell (EC) surfaces at all time intervals; conversely, allografts exhibited extensive EC loss at 1-2 weeks with gradual reparation by 10-12 weeks (such that the EC surface was virtually indistinguishable from that of control veins or autografts). PGI2 production was significantly greater in control arteries than veins (p = 0.0001). At 1-2 weeks and 4-6 weeks, lumenal production of PGI2 in both the autografts and allografts was not significantly different from control vein; however, PGI2 production after 10-12 weeks was identical to normal arterial levels (and significantly [p less than 0.0044] higher than venous levels) in both basal and stimulated conditions. Although the mechanisms responsible for this functional (biochemical) "arterialization" process remain conjectural, increased biosynthesis and/or release of PGI2 by endothelial cells, acute phase inflammatory cells (allografts) mediated by interleukin-1 or myointimal cells seems most likely. Further elucidation of these sources of PGI2 is necessary, but these data demonstrate for the first time that venous grafts placed in the arterial circulation undergo complete functional adaptation (in addition to the well known morphological changes).