Augmentation of wall shear stress inhibits neointimal hyperplasia after stent implantation: inhibition through reduction of inflammation?
BACKGROUND
Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent.


RESULTS
In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S+ARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m2 in the S+ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus]0.23+/-0.22 versus [minus]0.58+/-0.30 mm, P=0.02), (2) reduction in NH (1.48+/-0.58, 2.46+/-1.25, and 2.36+/-1.13 mm2, P<0.01, respectively, for S+ARED, S[minus]ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH.


CONCLUSIONS
The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.
Thoraxcentre, Erasmus Medical Center Rotterdam, Netherlands.
Stéphane G
SG
Carlier
Luc C A
LC
van Damme
Casper P
CP
Blommerde
Jolanda J
JJ
Wentzel
Glenn
G
van Langehove
Stephan
S
Verheye
Mark M
MM
Kockx
Michiel W M
MW
Knaapen
Caroline
C
Cheng
Frank
F
Gijsen
Dirk J
DJ
Duncker
Nikos
N
Stergiopulos
Cornelis J
CJ
Slager
Patrick W
PW
Serruys
Rob
R
Krams
D000818:Animals; D001783:Blood Flow Velocity; D019917:Blood Vessel Prosthesis Implantation; D002791:Cholesterol, Dietary / Q000494:pharmacology; D017023:Coronary Angiography; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007083:Iliac Artery / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D015607:Stents / Q000009:adverse effects; D013314:Stress, Mechanical; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology*; D014654:Vascular Patency / Q000187:drug effects
D002791:Cholesterol, Dietary