Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery

Changyi Chen; Stephen R. Hanson; Larry K. Keefer; Joseph E. Saavedra; Keith M. Davies; Thomas C. Hutsell; John D. Hughes; David N. Ku; Alan B. Lumsden

doi:10.1006/jsre.1996.4915

Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery

Changyi Chen, Stephen R. Hanson, Larry K. Keefer, Joseph E. Saavedra, Keith M. Davies, Thomas C. Hutsell, John D. Hughes, David N. Ku, Alan B. Lumsden

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	26-32
Number of pages	7
Journal	Journal of Surgical Research
Volume	67
Issue number	1
DOIs	https://doi.org/10.1006/jsre.1996.4915
State	Published - Jan 1997

ASJC Scopus subject areas

Surgery

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10.1006/jsre.1996.4915

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@article{fef2db1357ac46b8b9140cfaab21a835,

title = "Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery",

abstract = "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.",

author = "Changyi Chen and Hanson, {Stephen R.} and Keefer, {Larry K.} and Saavedra, {Joseph E.} and Davies, {Keith M.} and Hutsell, {Thomas C.} and Hughes, {John D.} and Ku, {David N.} and Lumsden, {Alan B.}",

note = "Funding Information: We thank Ms. Connie Miko for her expert technical assistance in tissue processing and histology procedures and Ms. Beverly Noe for her laboratory assistance. This study is supported in part by Research Grants HL 31469 and HL 48667 from the National Institutes of Health and by a grant from the American Heart Association.",

year = "1997",

month = jan,

doi = "10.1006/jsre.1996.4915",

language = "English (US)",

volume = "67",

pages = "26--32",

journal = "Journal of Surgical Research",

issn = "0022-4804",

publisher = "Academic Press",

number = "1",

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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.

N1 - Funding Information: We thank Ms. Connie Miko for her expert technical assistance in tissue processing and histology procedures and Ms. Beverly Noe for her laboratory assistance. This study is supported in part by Research Grants HL 31469 and HL 48667 from the National Institutes of Health and by a grant from the American Heart Association.

PY - 1997/1

Y1 - 1997/1

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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Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery

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