REDUCED PROSTACYCLIN AND INCREASED LEUKOTRIENE B-4 SYNTHESIS IN PORCINE VENOUS ARTERIAL GRAFTS

Background. Migration and proliferation of vascular smooth muscle cell s in the intima and superimposed atheroma are the main changes underly ing late failure of saphenous vein bypass grafts. There is evidence th at these events are partly modulated by complex interactions between i nhibitors of vascular smooth muscle cell proliferation, such as prosta cyclin (PGI(2)), and mitogens, such as leukotriene B-4 (LTB(4)). Becau se the relative balance between these eicosanoids may play a role in v ein,graft failure, the synthesis of PGI(2) and LTB(4) was measured in porcine saphenous vein-carotid artery grafts 4 weeks after implantatio n and compared with ungrafted vein and common carotid artery from the same animal. Methods. Vessels were cut into 2-mm squares and preincuba ted in Dulbecco's minimum essential medium for 4 hours at 37 degrees C . Tissues were then further incubated with Dulbecco's minimum essentia l medium containing a range of concentrations of noradrenaline, arachi donate, and calcium ionophore A23187. Release of PGI(2) and LTB(4) int o the supernatant was then assessed by radioimmunoassay. Results. In r esponse to all stimulators, PGI(2) release was markedly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteri es. The patterns of responses were similar in each vessel type. In con trast, LTB(4) release was significantly enhanced in vein grafts compar ed to ungrafted saphenous veins and carotid arteries. Conclusions. The se data indicate that there is a downregulation of cyclooxygenase or P GI(2) synthase in porcine vein grafts, which may constitute a further phenotypic change that would augment the hyperplastic process. Local i ncreases in LTB(4) synthesis in the vein graft, which indicates an ind uction of lipoxygenase and LTB(4) synthase enzymes (and possibly refle cts release from leukocytes which have infiltrated the graft), may con tribute to increased intimal proliferation by direct promitogenic effe cts on smooth muscle cells.