人体大隐静脉桥外膜戊二醛交联对其生物力学特性的影响
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摘要
背景:薄弱的静脉壁是冠状动脉旁路移植术后大隐静脉桥病变的诱发因素之一。目的:探讨人体大隐静脉桥外膜戊二醛交联对血管生物力学特性的影响。方法:收集冠状动脉粥样硬化性心脏病患者冠状动脉旁路移植术后剩余的大隐静脉40段,随机分A、B组,每组20段,将A组中的每段大隐静脉分成2小段,其中一段采用0.3%戊二醛溶液交联5min,另一段不交联(对照);将B组的每段大隐静脉分成2小段,其中一段采用0.3%戊二醛溶液交联10 min,另一段不交联(对照)。采用荧光显微镜及扫描电镜观察交联前后的血管壁微观形态;利用单轴拉伸测试检测交联前后血管的应力-应变关系、杨氏模量及破坏强度。结果与结论:(1)荧光显微镜:与对照血管相比,交联血管的Ⅰ型胶原纤维呈明显压缩改变,密度显著增大,管腔面结构未见明显差异;(2)扫描电镜:对照血管外膜表面胶原纤维呈现典型的波浪状疏松排列,交联血管外膜表面胶原纤维呈现致密的网状排列;(3)单轴拉伸测试:与对照血管比较,交联5,10min血管的应力-应变曲线明显左移,并且在高应变区(延展率为1.3-1.5)杨氏模量显著增加(P <0.05);与交联5 min血管比较,交联10 min血管的应力-应变曲线明显左移,并且在高应变区(延展率为1.3-1.5)杨氏模量显著增加(P <0.05);交联5,10 min血管的破坏强度高于对照血管(P <0.05);(4)结果表明:血管外膜戊二醛交联增加了大隐静脉血管壁强度,降低了其延展性。
BACKGROUND: Poor venous wall is one of the inducing factors causing saphenous vein failure after coronary artery bypass grafting(CABG).OBJECTIVE: To explore the effects of adventitial glutaraldehyde cross-linking on the biomechanical properties of human saphenous vein graft(SVG). METHODS: Forty residual segments of SVG were collected from the patients undergoing CABG. Those segments were randomly divided into group A(n=20) and group B(n=20). Adventitial cross-linking was performed with 0.3% glutaraldehyde solution. Each SVG segment in group A was equally subdivided into two parts: one for adventitial cross-linking 5 minutes and the other as self-control. Each SVG segment in group B was also equally subdivided into two parts: one for adventitial cross-linking 10 minutes and the other as self-control. The ultra-structural changes of the venous wall with or without cross-linking were observed by fluorescence microscope and scanning electron microscope. The SVG segments in two groups underwent the uniaxial stretch test to detect the stress-strain relationship, Young's elastic modulus and breaking strength of SVG segments receiving different processing. RESULTS AND CONCLUSION:(1) Fluorescence microscope: Compared with the SVGs of self-control, cross-linked SVGs mainly presented with compacted adventitial monomer of collagen and increased density of type I collagen, without obvious ultra-structural changes in the lumen surface.(2) Scanning electron microscope: The adventitial collagen fibers in the self-control segments showed a typical wavy loose arrangement, while the adventitial collagen fibers in the cross-linked segment appeared to have a dense fibrous network.(3) Uniaxial stretch test: Compared with the self-control parts, the stress-stretch ratio curve in the cross-linked parts in the two groups was shifted to the left remarkably, and in the high strain region(stretch ratio 1.3-1.5), the Young's elastic modulus was also increased significantly(P < 0.05). Compared with the SVGs in the cross-linking 5 minutes, the stress-stretch ratio curve in the SVGs in the cross-linking 10 minutes was shifted to the left remarkably, and in the high strain region(stretch ratio 1.3-1.5), the Young's elastic modulus was also increased significantly(P < 0.05). The breaking strength of cross-linked SVGs was higher than that of self-control SVGs in the two groups(P < 0.05). To conclude, adventitial glutaraldehyde cross-linking reinforces venous wall and reduces the ductility of human SVG.
BACKGROUND: Poor venous wall is one of the inducing factors causing saphenous vein failure after coronary artery bypass grafting(CABG).OBJECTIVE: To explore the effects of adventitial glutaraldehyde cross-linking on the biomechanical properties of human saphenous vein graft(SVG). METHODS: Forty residual segments of SVG were collected from the patients undergoing CABG. Those segments were randomly divided into group A(n=20) and group B(n=20). Adventitial cross-linking was performed with 0.3% glutaraldehyde solution. Each SVG segment in group A was equally subdivided into two parts: one for adventitial cross-linking 5 minutes and the other as self-control. Each SVG segment in group B was also equally subdivided into two parts: one for adventitial cross-linking 10 minutes and the other as self-control. The ultra-structural changes of the venous wall with or without cross-linking were observed by fluorescence microscope and scanning electron microscope. The SVG segments in two groups underwent the uniaxial stretch test to detect the stress-strain relationship, Young's elastic modulus and breaking strength of SVG segments receiving different processing. RESULTS AND CONCLUSION:(1) Fluorescence microscope: Compared with the SVGs of self-control, cross-linked SVGs mainly presented with compacted adventitial monomer of collagen and increased density of type I collagen, without obvious ultra-structural changes in the lumen surface.(2) Scanning electron microscope: The adventitial collagen fibers in the self-control segments showed a typical wavy loose arrangement, while the adventitial collagen fibers in the cross-linked segment appeared to have a dense fibrous network.(3) Uniaxial stretch test: Compared with the self-control parts, the stress-stretch ratio curve in the cross-linked parts in the two groups was shifted to the left remarkably, and in the high strain region(stretch ratio 1.3-1.5), the Young's elastic modulus was also increased significantly(P < 0.05). Compared with the SVGs in the cross-linking 5 minutes, the stress-stretch ratio curve in the SVGs in the cross-linking 10 minutes was shifted to the left remarkably, and in the high strain region(stretch ratio 1.3-1.5), the Young's elastic modulus was also increased significantly(P < 0.05). The breaking strength of cross-linked SVGs was higher than that of self-control SVGs in the two groups(P < 0.05). To conclude, adventitial glutaraldehyde cross-linking reinforces venous wall and reduces the ductility of human SVG.
引文
[1]Goldman S,Zadina K,Moritz T,et al.Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery:results from a Department of Veterans Affairs Cooperative Study.J Am Coll Cardiol.2004;44(11):2149-2156.
[2]Harskamp RE,Lopes RD,Baisden CE,et al.Saphenous vein graft failure after coronary artery bypass surgery:pathophysiology,management,and future directions.Ann Surg.2013;257(5):824-833.
[3]Gooch KJ,Firstenberg MS,Shrefler BS,et al.Biomechanics and Mechanobiology of Saphenous Vein Grafts.J Biomech Eng.2018;140(2).doi:10.1115/1.34038705.
[4]Parsonnet V,Lari AA,Shah IH.New Stent for Support of Veins in Arterial Grafts.Arch Surg.1963;87:696-702.
[5]Taggart DP,Ben Gal Y,Lees B,et al.A Randomized Trial of External Stenting for Saphenous Vein Grafts in Coronary Artery Bypass Grafting.Ann Thorac Surg.2015;99(6):2039-2045.
[6]Angelini GD,Lloyd C,Bush R,et al.An external,oversized,porous polyester stent reduces vein graft neointima formation,cholesterol concentration,and vascular cell adhesion molecule 1 expression in cholesterol-fed pigs.J Thorac Cardiovasc Surg.2002;124(5):950-956.
[7]Goldstone RN,McCormack MC,Khan SI,et al.Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting.J Am Heart Assoc.2016;5(8).pii:e003856.doi:10.1161/JAHA.116.003856.
[8]Chandran PL,Paik DC,Holmes JW.Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking.Connect Tissue Res.2012;53(4):285-297.
[9]Van de Walle AB,Uzarski JS,McFetridge PS.The consequence of biologic graft processing on blood interface biocompatibility and mechanics.Cardiovasc Eng Technol.2015;6(3):303-313.
[10]Authors/Task Force members,Windecker S,Kolh P,et al.2014ESC/EACTS Guidelines on myocardial revascularization:The Task Force on Myocardial Revascularization of the European Society of Cardiology(ESC)and the European Association for Cardio-Thoracic Surgery(EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions(EAPCI).Eur Heart J.2014;35(37):2541-2619.
[11]Hamedani BA,Navidbakhsh M,Tafti HA.Comparison between mechanical properties of human saphenous vein and umbilical vein.Biomed Eng Online.2012;11:59.
[12]Leask RL,Butany J,Johnston KW,et al.Human saphenous vein coronary artery bypass graft morphology,geometry and hemodynamics.Ann Biomed Eng.2005;33(3):301-309.
[13]Teng ZZ,Ji GY,Chu HJ,et al.Does PGA external stenting reduce compliance mismatch in venous grafts?Biomed Eng Online.2007;6:12.
[14]Ishiwata S,Tukada T,Nakanishi S,et al.Postangioplasty restenosis:platelet activation and the coagulation-fibrinolysis system as possible factors in the pathogenesis of restenosis.Am Heart J.1997;133(4):387-392.
[15]Nguyen HC,Grossi EA,LeBoutillier M,3rd,et al.Mammary artery versus saphenous vein grafts:assessment of basic fibroblast growth factor receptors.Ann Thorac Surg.1994;58(2):308-310.
[16]Turner NA,Hall KT,Ball SG,et al.Selective gene silencing of either MMP-2 or MMP-9 inhibits invasion of human saphenous vein smooth muscle cells.Atherosclerosis.2007;193(1):36-43.
[17]Kim FY,Marhefka G,Ruggiero NJ,et al.Saphenous vein graft disease:review of pathophysiology,prevention,and treatment.Cardiol Rev.2013;21(2):101-109.
[18]Goissis G,Yoshioka SA,Braile DM,et al.The chemical protecting group concept applied in crosslinking of natural tissues with glutaraldehyde acetals.Artif Organs.1998;22(3):210-214.
[19]Zilla P,Bezuidenhout D,Weissenstein C,et al.Diamine extension of glutaraldehyde crosslinks mitigates bioprosthetic aortic wall calcification in the sheep model.J Biomed Mater Res.2001;56(1):56-64.
[20]Kim KM,Herrera GA,Battarbee HD.Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts.Am J Pathol.1999;154(3):843-852.
[21]Wine Y,Cohen-Hadar N,Freeman A,et al.Elucidation of the mechanism and end products of glutaraldehyde crosslinking reaction by X-ray structure analysis.Biotechnol Bioeng.2007;98(3):711-718.
[22]Cheung DT,Perelman N,Ko EC,et al.Mechanism of crosslinking of proteins by glutaraldehyde III.Reaction with collagen in tissues.Connect Tissue Res.1985;13(2):109-115.
[23]Angelini GD,Breckenridge IM,Butchart EG,et al.Metabolic damage to human saphenous vein during preparation for coronary artery bypass grafting.Cardiovasc Res.1985;19(6):326-334.
[24]Angelini GD,Soyombo AA,Newby AC.Winner of the ESVSprize 1990.Smooth muscle cell proliferation in response to injury in an organ culture of human saphenous vein.Eur JVasc Surg.1991;5(1):5-12.
[2]Harskamp RE,Lopes RD,Baisden CE,et al.Saphenous vein graft failure after coronary artery bypass surgery:pathophysiology,management,and future directions.Ann Surg.2013;257(5):824-833.
[3]Gooch KJ,Firstenberg MS,Shrefler BS,et al.Biomechanics and Mechanobiology of Saphenous Vein Grafts.J Biomech Eng.2018;140(2).doi:10.1115/1.34038705.
[4]Parsonnet V,Lari AA,Shah IH.New Stent for Support of Veins in Arterial Grafts.Arch Surg.1963;87:696-702.
[5]Taggart DP,Ben Gal Y,Lees B,et al.A Randomized Trial of External Stenting for Saphenous Vein Grafts in Coronary Artery Bypass Grafting.Ann Thorac Surg.2015;99(6):2039-2045.
[6]Angelini GD,Lloyd C,Bush R,et al.An external,oversized,porous polyester stent reduces vein graft neointima formation,cholesterol concentration,and vascular cell adhesion molecule 1 expression in cholesterol-fed pigs.J Thorac Cardiovasc Surg.2002;124(5):950-956.
[7]Goldstone RN,McCormack MC,Khan SI,et al.Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting.J Am Heart Assoc.2016;5(8).pii:e003856.doi:10.1161/JAHA.116.003856.
[8]Chandran PL,Paik DC,Holmes JW.Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking.Connect Tissue Res.2012;53(4):285-297.
[9]Van de Walle AB,Uzarski JS,McFetridge PS.The consequence of biologic graft processing on blood interface biocompatibility and mechanics.Cardiovasc Eng Technol.2015;6(3):303-313.
[10]Authors/Task Force members,Windecker S,Kolh P,et al.2014ESC/EACTS Guidelines on myocardial revascularization:The Task Force on Myocardial Revascularization of the European Society of Cardiology(ESC)and the European Association for Cardio-Thoracic Surgery(EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions(EAPCI).Eur Heart J.2014;35(37):2541-2619.
[11]Hamedani BA,Navidbakhsh M,Tafti HA.Comparison between mechanical properties of human saphenous vein and umbilical vein.Biomed Eng Online.2012;11:59.
[12]Leask RL,Butany J,Johnston KW,et al.Human saphenous vein coronary artery bypass graft morphology,geometry and hemodynamics.Ann Biomed Eng.2005;33(3):301-309.
[13]Teng ZZ,Ji GY,Chu HJ,et al.Does PGA external stenting reduce compliance mismatch in venous grafts?Biomed Eng Online.2007;6:12.
[14]Ishiwata S,Tukada T,Nakanishi S,et al.Postangioplasty restenosis:platelet activation and the coagulation-fibrinolysis system as possible factors in the pathogenesis of restenosis.Am Heart J.1997;133(4):387-392.
[15]Nguyen HC,Grossi EA,LeBoutillier M,3rd,et al.Mammary artery versus saphenous vein grafts:assessment of basic fibroblast growth factor receptors.Ann Thorac Surg.1994;58(2):308-310.
[16]Turner NA,Hall KT,Ball SG,et al.Selective gene silencing of either MMP-2 or MMP-9 inhibits invasion of human saphenous vein smooth muscle cells.Atherosclerosis.2007;193(1):36-43.
[17]Kim FY,Marhefka G,Ruggiero NJ,et al.Saphenous vein graft disease:review of pathophysiology,prevention,and treatment.Cardiol Rev.2013;21(2):101-109.
[18]Goissis G,Yoshioka SA,Braile DM,et al.The chemical protecting group concept applied in crosslinking of natural tissues with glutaraldehyde acetals.Artif Organs.1998;22(3):210-214.
[19]Zilla P,Bezuidenhout D,Weissenstein C,et al.Diamine extension of glutaraldehyde crosslinks mitigates bioprosthetic aortic wall calcification in the sheep model.J Biomed Mater Res.2001;56(1):56-64.
[20]Kim KM,Herrera GA,Battarbee HD.Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts.Am J Pathol.1999;154(3):843-852.
[21]Wine Y,Cohen-Hadar N,Freeman A,et al.Elucidation of the mechanism and end products of glutaraldehyde crosslinking reaction by X-ray structure analysis.Biotechnol Bioeng.2007;98(3):711-718.
[22]Cheung DT,Perelman N,Ko EC,et al.Mechanism of crosslinking of proteins by glutaraldehyde III.Reaction with collagen in tissues.Connect Tissue Res.1985;13(2):109-115.
[23]Angelini GD,Breckenridge IM,Butchart EG,et al.Metabolic damage to human saphenous vein during preparation for coronary artery bypass grafting.Cardiovasc Res.1985;19(6):326-334.
[24]Angelini GD,Soyombo AA,Newby AC.Winner of the ESVSprize 1990.Smooth muscle cell proliferation in response to injury in an organ culture of human saphenous vein.Eur JVasc Surg.1991;5(1):5-12.