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Gaps in the internal elastic lamina (IEL) have been observed in arteries exposed to high blood flow. To characterize the nature and consequences of this change, blood flow was increased in the carotid arteries of 56 adult, male, Japanese white rabbits by creating an arteriovenous fistula between the common carotid artery and the external jugular vein. The common carotid artery proximal to the arteriovenous fistula was studied at intervals from 1 hour to 8 weeks after exposure to high flow. In the controls, the IEL showed only the usual, small, physiological holes, 2 to 10 microm in diameter. At 3 days, some of the holes in the IEL had become enlarged, but they could not be detected by scanning electron microscopy, despite manifest endothelial cell proliferation. At 4 days, gaps in the IEL appeared as small, luminal surface depressions, 15 to 50 microm wide. At 7 days, the gaps in the IEL had enlarged and formed circumferential, luminal depressions occupying 15+/-5% of the lumen surface. Endothelial cell proliferation persisted in the gaps while proliferative activity decreased where the IEL remained intact. At 4 weeks, as the artery became elongated and dilated, the gaps in the IEL widened as intercommunicating circumferential and longitudinal luminal depressions occupying 64+/-5% of the lumen surface. At 8 weeks, the rate of elongation and dilatation of the artery slowed and the widening of the gaps in the IEL diminished. Endothelial cells covered the gaps throughout. We conclude that flow-induced arterial dilatation is accompanied by an adaptive remodeling of the intima. The gaps in the IEL permit an increase in lumen surface area while endothelial cell proliferation assures a continuous cell lining throughout.

This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

Abstract-We investigated apoptosis of endothelial cells during the arterial narrowing process in response to reduction in flow. The decrease in flow was created in the carotid artery by closure of an arteriovenous fistula (AVF), which had been established for 28 days in rabbits. The endothelial cell apoptosis in the carotid artery was studied at 1, 3, 7, and 21 days of flow reduction after closure of the AVF by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with laser scanning confocal microscopy and transmission and scanning electron microscopy. After AVF closure, arterial lumen diameter was reduced by 36%, and compared with endothelial cells before the closure, the number of endothelial cells was decreased by 45% at 21 days. Endothelial cell apoptosis was observed at 1 day, peaked at 3 days (381.3Ϯ87.1 cells per square millimeter), and decreased at 7 days. These cells had irregular protrusions under scanning electron microscopy and were characterized by fragmented nuclei under transmission electron microscopy. Apoptotic cells were mainly beneath the endothelium and were occasionally within smooth muscle cells and endothelial cells. The results suggest that apoptosis of endothelial cells may play a role in the arterial remodeling in response to a reduction in flow.

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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.

Cell proliferation was stimulated at 3 days, and apoptosis was halted until 4 weeks. These changes were associated with upregulation of TGF-beta and downregulation of Bcl-xS and Fas ligand gene expression. These findings suggest that a coordinated regulation of cell proliferation and cell death contributes to arterial remodeling in response to acute sustained elevation of blood pressure. Cell proliferation precedes apoptosis by 2 weeks in this procedure.

No abstract