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Ann Thorac Surg 1996;61:143-148
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Reduced Prostacyclin and Increased Leukotriene B₄ Synthesis in Porcine Venous-Arterial Grafts

Bristol Heart Institute, University of Bristol, Bristol, United Kingdom

Accepted for publication September 5, 1995.

Background. Migration and proliferation of vascular smooth muscle cells in the intima and superimposed atheroma are the main changes underlying late failure of saphenous vein bypass grafts. There is evidence that these events are partly modulated by complex interactions between inhibitors of vascular smooth muscle cell proliferation, such as prostacyclin (PGI₂), and mitogens, such as leukotriene B₄ (LTB₄). Because the relative balance between these eicosanoids may play a role in vein graft failure, the synthesis of PGI₂ and LTB₄ was measured in porcine saphenous vein-carotid artery grafts 4 weeks after implantation and compared with ungrafted vein and common carotid artery from the same animal.

Methods. Vessels were cut into 2-mm squares and preincubated in Dulbecco's minimum essential medium for 4 hours at 37°C. Tissues were then further incubated with Dulbecco's minimum essential medium containing a range of concentrations of noradrenaline, arachidonate, and calcium ionophore A23187. Release of PGI₂ and LTB₄ into the supernatant was then assessed by radioimmunoassay.

Results. In response to all stimulators, PGI₂ release was markedly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. The patterns of responses were similar in each vessel type. In contrast, LTB₄ release was significantly enhanced in vein grafts compared to ungrafted saphenous veins and carotid arteries.

Conclusions. These data indicate that there is a down-regulation of cyclooxygenase or PGI₂ synthase in porcine vein grafts, which may constitute a further phenotypic change that would augment the hyperplastic process. Local increases in LTB₄ synthesis in the vein graft, which indicates an induction of lipoxygenase and LTB₄ synthase enzymes (and possibly reflects release from leukocytes which have infiltrated the graft), may contribute to increased intimal proliferation by direct promitogenic effects on smooth muscle cells.

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