Responsiveness of vein bypass grafts to stimulation with norepinephrine and 5-hydroxytryptamine

The in vitro reactivity of vein bypass grafts to norepinephrine (NE) and 5-hydroxytryptamine (5-HT) was studied in 20 rabbits undergoing bypass grafting. In these animals the right external jugular vein was grafted into the right carotid artery. The cumulative dose-response to NE and 5-HT of rings of vein grafts 2, 4, and 6 weeks after insertion was compared with that of rings from the normal contralateral jugular vein by means of an organ bath to measure changes in isometric tension. With NE there was no significant difference in the response of vein grafts harvested at 2 weeks and control veins. However, at 4 and 6 weeks there was a progressive decrease in the sensitivity of the grafts to NE. The difference in ED50 values (ED50 defined as concentration of agonist required to elicit 50% of the maximal response) between control veins and vein grafts at 4 weeks was twofold and at 6 weeks it was fivefold. None of the control veins responded to 5-HT stimulation. However, the vein grafts contracted with 5-HT, exhibiting sigmoid dose-response curves. The vein grafts showed intimal hyperplasia, which was maximal after 4 weeks. These results show that vein grafts undergo a progressive decrease in their sensitivity to norepinephrine and develop a marked, sustained increase in sensitivity to 5-HT. This finding is in contrast to previous observations in intimal hyperplastic rabbit aorta, suggesting a fundamental difference in the functional expression of arterial and venous intimal hyperplasia.