Sequential increases and decreases in blood flow stimulates progressive intimal thickening.

Abstract

To assess the effect of chronic, repetitive increases and decreases in blood flow on an artery. Arteriovenous fistulae were created in Japanese male rabbits between the left common carotid artery and the corresponding external jugular vein. Animals were placed into either control groups or one of six cycle groups consisting of flow variations (0.5 cycles, 1.0 cycle, 1.5 cycles, 2.0 cycles, 2.5 cycles and 3.0 cycles). Each complete cycle consisted of 4 weeks of increased flow followed by 6 weeks of normalised flow by fistula ligation. Arteries exposed to increased flow for 4 weeks (0.5 cycles) had a significant increase in lumen diameter without intimal thickening. After 6 weeks of normalised flow (1.0 cycle), shear stress became subnormal (0.42 +/- 0.17 N/m2), intimal thickening developed. In subsequent cycles, intimal thickening continued to develop with each point of flow normalisation and reduction in shear stress. Histologic and ultrastructural analysis revealed endothelial cells preservation at all time points, with individual strata of smooth muscle cell proliferation in the intima corresponding to the cycle numbers. Progressive intimal thickening occurred in the previously flow-induced remodelled artery when shear stress was reduced to subnormal levels with preserved endothelium, but was inhibited by high flow periods.