TY - JOUR
T1 - Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery
AU - Chen, Changyi
AU - Hanson, Stephen R.
AU - Keefer, Larry K.
AU - Saavedra, Joseph E.
AU - Davies, Keith M.
AU - Hutsell, Thomas C.
AU - Hughes, John D.
AU - Ku, David N.
AU - Lumsden, Alan B.
PY - 1997/1/1
Y1 - 1997/1/1
N2 - To evaluate the direct effect of nitric oxide (NO) on vascular smooth muscle cell (SMC) proliferation in vivo, we used an expanded polytetrafluoroethylene (ePTFE)-based local infusion device to deliver an NO donor, proline/NO (PROLI/NO), to the luminal boundary layer of endarterectomized artery and the distal anastomosis of the graft in a canine model. Once delivered to the blood, PROLI/NO releases NO by a mechanism involving pH-dependent decomposition. Six dogs underwent bilateral femoral artery endarterectomies. ePTFE infusion devices, blindly primed with PROLI/NO to one artery or proline to the contralateral vessel, were anastomosed proximal to the injured segments so that each animal served as its own control. PROLI/NO or proline was continuously delivered for 7 days from an osmotic reservoir, through the wall of the graft infusion device. Euthanasia was carried out at 7 days, and the processed specimens were blindly analyzed for SMC proliferation at both graft anastomoses and endarterectomized segments by a bromodeoxyuridine index assay. All dogs survived with no clinical side effects. In comparing the treated and control vessels, NO released from PROLI/NO significantly reduced SMC proliferation by 43% (13.24 ± 1.24% versus 23.24 ± 1.01%, P = 0.004) at the distal anastomoses and by 68% (10.58 ± 1.63% versus 25.17 ± 3.39%, P = 0.007) at endarterectomized segments. However, there was no significant difference in blood flow measurements between treated and control arteries (56.25 ± 6.50 ml/min versus 46.50 ± 3.20 ml/min, P = 0.094). These data demonstrate that local boundary layer infusion of NO released from PROLI/NO significantly reduces SMC proliferation in injured arteries with no effect on regional blood flow. This study suggests a new strategy to inhibit early SMC proliferation in injured arteries and probably to control intimal hyperplastic lesion formation in the manipulated vessels.
AB - To evaluate the direct effect of nitric oxide (NO) on vascular smooth muscle cell (SMC) proliferation in vivo, we used an expanded polytetrafluoroethylene (ePTFE)-based local infusion device to deliver an NO donor, proline/NO (PROLI/NO), to the luminal boundary layer of endarterectomized artery and the distal anastomosis of the graft in a canine model. Once delivered to the blood, PROLI/NO releases NO by a mechanism involving pH-dependent decomposition. Six dogs underwent bilateral femoral artery endarterectomies. ePTFE infusion devices, blindly primed with PROLI/NO to one artery or proline to the contralateral vessel, were anastomosed proximal to the injured segments so that each animal served as its own control. PROLI/NO or proline was continuously delivered for 7 days from an osmotic reservoir, through the wall of the graft infusion device. Euthanasia was carried out at 7 days, and the processed specimens were blindly analyzed for SMC proliferation at both graft anastomoses and endarterectomized segments by a bromodeoxyuridine index assay. All dogs survived with no clinical side effects. In comparing the treated and control vessels, NO released from PROLI/NO significantly reduced SMC proliferation by 43% (13.24 ± 1.24% versus 23.24 ± 1.01%, P = 0.004) at the distal anastomoses and by 68% (10.58 ± 1.63% versus 25.17 ± 3.39%, P = 0.007) at endarterectomized segments. However, there was no significant difference in blood flow measurements between treated and control arteries (56.25 ± 6.50 ml/min versus 46.50 ± 3.20 ml/min, P = 0.094). These data demonstrate that local boundary layer infusion of NO released from PROLI/NO significantly reduces SMC proliferation in injured arteries with no effect on regional blood flow. This study suggests a new strategy to inhibit early SMC proliferation in injured arteries and probably to control intimal hyperplastic lesion formation in the manipulated vessels.
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U2 - 10.1006/jsre.1996.4915
DO - 10.1006/jsre.1996.4915
M3 - Article
C2 - 9070177
AN - SCOPUS:0030998144
VL - 67
SP - 26
EP - 32
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 1
ER -