The effects of extremely low shear stress on cellular proliferation and neointimal thickening in the failing bypass graft

Shari L. Meyerson*, Christopher L. Skelly, Michael A. Curi, Umar M. Shakur, James E. Vosicky, Seymour Glagov, Lewis B. Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Objective: Previous studies demonstrating a correlation between low shear stress (τ = 5-15 dyne/cm2) and experimental vein graft neointimal thickening (NIT) support the role of low τ in vein graft failure. However, a simple linear relationship between low t and NIT would underestimate the degree of NIT evident in high-grade occlusive lesions of failing human vein grafts. In this study we used a new experimental model that maintains patency at low τ (< 2 dyne/cm2), to delineate possible deviations from linearity in the low τ → NIT hypothesis. Methods: Thirty-two New Zealand White rabbits underwent creation of a common carotid vein patch with a segment of ipsilateral external jugular vein. Very low τ was created in 13 patches by ligation of the distal common carotid artery, leaving the only outflow through a small muscular branch. Normal τ was created hi 11 patches by leaving the common carotid artery outflow intact. High τ was created in eight patches by ligation of the contralateral common carotid artery. Six patches were harvested after 2 weeks for measurement of cell cycle entry by proliferating cell nuclear antigen (PCNA) immunohistochemistry. The remaining 26 patches were harvested after 4 weeks, perfusion fixed, and excised for morphometric analysis. Results: Mean blood flow and τ at implantation ranged from 0.5 to 41 mL/min and 0.07 to 15 dyne/cm2, respectively. At the time of harvest, 30 of 32 patches remained patent, and the artificially created aberrations in blood flow were maintained (range, 0.7-41 mL/min). After 2 weeks PCNA immunohistochemistry showed a significantly higher level of cell cycling in patches exposed to low τ (40 ± 5 vs 1.6 ± 0.3 PCNA-positive cells per high-power field; P < .001), which is equivalent to approximately 20% of the total cells present. In patches harvested after 4 weeks, NIT ranged from 42 to 328 μm and significantly correlated with mean τ at implantation. Patches with very low τ exhibited histologic characteristics similar to those of failing human bypass grafts, including laminar thrombus and flow-limiting luminal stenosis. The relationship between τ and NIT was nonlinear in that extremely low τ (<; 2 dyne/cm2) resulted in NIT beyond that predicted by a simple linear correlation (P = .003). Conclusion: Extremely low τ (<; 2 dyne/cm2) stimulates high rates of smooth muscle cellular proliferation in arterialized vein patches. NIT is accelerated in these regions of low τ far beyond that predicted by a simple linear model. The nonlinear nature of the cellular proliferative response and NIT at τ less than 2 dyne/cm2 may explain the rapid progression of neointimal lesions in failing bypass grafts.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalJournal of Vascular Surgery
Issue number1
StatePublished - Jul 2001

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'The effects of extremely low shear stress on cellular proliferation and neointimal thickening in the failing bypass graft'. Together they form a unique fingerprint.

Cite this