Human saphenous vein grafts explanted from the arterial circulation demonstrate altered smooth-muscle and endothelial responses

Abstract

Animal models have been used to assess the function of vascular smooth muscle and endothelium of veins grafted into arterial circulation. The primary model consists of grafting the external jugular vein into the carotid artery of the rabbit. These studies suggest a selective increase in the responsiveness of the grafted veins to serotonin. However, in both human cardiac and peripheral vascular operations, the saphenous, not the jugular, is the vein most frequently used. Thus the propriety of the rabbit model is unknown. Human saphenous veins and vein grafts were obtained from patients undergoing leg vein bypass graft revisions (n = 8). The reversed vein grafts were placed into arterial circulation for periods ranging from 4 to 26 months before removal (mean 16 months). All vessels were immediately cut into rings and suspended in organ chambers for recording isometric contractions to norepinephrine and serotonin. The maximal contractions elicited by both norepinephrine and serotonin were reduced in human vein grafts in comparison to the results in human saphenous vein (maximal response to norepinephrine 1.42 +/- 0.34 gm [vein graft] vs 4.59 +/- 1.13 gm [saphenous vein], p = 0.031; maximal response to serotonin 2.68 +/- 0.58 gm [vein graft] vs 4.72 +/- 1.11 gm [saphenous vein], p = 0.042). Human vein grafts were less responsive to norepinephrine than was saphenous vein (negative log of concentration that caused 50% of the maximal response -5.91 +/- 0.10 and -6.84 +/- 0.22, respectively; p < 0.009). After precontraction with norepinephrine (to 30% of the maximal response), saphenous vein, but not vein grafts, demonstrated endothelium-dependent relaxation to acetylcholine (maximum relaxation 27.4% +/- 6.8%; p = 0.001). Human saphenous veins grafted into arterial circulation exhibit loss of endothelium-dependent relaxation to acetylcholine and diminished contractions to agonists (norepinephrine and serotonin). In contrast to rabbit data, serotonin elicits dose-dependent contractions in both human saphenous vein and human vein grafts. Since the vascular wall contractility varies widely across species, the relevance of rabbit vein graft data to human bypass grafts is uncertain.