POSSIBLE MECHANISMS OF COLLAR-INDUCED INTIMAL THICKENING

The positioning of a soft silicone collar around the rabbit carotid ar tery induces intimal thickening. We investigated to which extent occlu sion of the vasa vasorum, damage of the perivascular nerve network, an d/or changes in blood flow velocity contribute to intimal thickening. To this end, collars with different bores (diameter of inlet and outle t) were positioned around the carotid artery of male rabbits for 14 da ys. In another experiment, 75% of the wall of fitting collars was remo ved (open collar). In the midcollar region, the cross-sectional area o f the intima reached a maximum (72+/-14 mm(2)/1000) when the endings o f the collar fitted the artery closely. Removal of the side wall of th ese fitting collars reduced intimal thickening by 90%. Examination of unoperated carotid arteries never showed penetration of the adventitia or the media by vasa vasorum. The perivascular neuronal network in th e region surrounded by a closed or an open collar was almost completel y lost as compared with the zones outside the collar. Both the closed and open collar slightly bent the artery and increased the peak systol ic velocity, measured with pulsed color Doppler after 6 hours, to a si milar extent as compared with the proximal zone outside the collar. Af ter 2 weeks, the peak systolic velocity within both the closed and ope n collar was partly normalized and was statistically not different fro m the proximal zone outside the collar. In conclusion, the geometry of the collar influenced the extent of intimal thickening, whereby more intimal thickening was obtained with a collar whose endings fit the ca rotid artery, rather than with a loose collar. Moreover, a closed stru cture was essential. The results obtained with the open collar exclude occlusion of vasa vasorum, damage of the perivascular neuronal networ k, kinking of the artery, and changes in blood flow velocity as major factors in the collar-induced intimal thickening. Our findings are con sistent with the possibility that intimal thickening is the consequenc e of the combination of both vascular injury and hindrance of transmur al flow by the collar. The obstruction of transmural fluid transport m ay then lead to retention of toxic metabolites, and/or cytokines withi n the segment enclosed by the collar.