Pre-bypass morphological changes in vein grafts

Davies, Alun H.; Magee, T.R.; Baird, R. N.; Sheffield, E.; Horrocks, M.

doi:10.1016/s0950-821x(05)80710-8

Cited by 50 publications

(31 citation statements)

References 22 publications

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“…Patient age, sex, and diabetes were not associated with the maximal intimal thickness of the native basilic vein, IH of the draining vein of the AVF, or the change in venous IH between paired vein samples from the same individual (10). Although vascular trauma from venipuncture and intravenous peripheral lines may contribute to preexisting vascular pathologies, it does not explain the extensive IH frequently found in distal saphenous veins that have never been punctured or traumatized (18).…”

Section: Ih Pathobiology Of Preexisting Ihmentioning

confidence: 82%

“…A seminal study showed a positive association between the degree of arterial intimal thickness and calcification and the duration of uremia (17). Nonetheless, similar pathologies have been observed in the cephalic and saphenous veins of elderly patients with normal renal function undergoing arterial grafting (18), suggesting that uremia is not the only biologic insult causing vascular intimal thickening in patients with CKD. Tabbara et al (10) obtained two consecutive basilic vein samples from patients undergoing a planned two-stage AVF: the first sample from the native vein used to create the AVF and the second one several weeks later from the draining vein of the AVF (Figure 1).…”

Section: Ih Pathobiology Of Preexisting Ihmentioning

confidence: 92%

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New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

Vázquez-Padrón

Allon

2016

CJASN

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Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.

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Section: Ih Pathobiology Of Preexisting Ihmentioning

confidence: 82%

Section: Ih Pathobiology Of Preexisting Ihmentioning

confidence: 92%

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

Vázquez-Padrón

Allon

2016

CJASN

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“…It has been suggested that distension of veins before implantation may induce a number of changes, 32 including the loss of cell-to-cell and cell-to-matrix contacts, muscle hypertrophy, and proliferation of circumferential VSMCs. 33,34 …”

Section: Resultsmentioning

confidence: 99%

Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein

Johnson

Eys

Angelini

et al. 2001

ATVB

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Abstract-Long-term patency of human saphenous vein bypass grafts is low because of intimal thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to be essential for the VSMC migration that contributes to intimal thickening. We examined VSMC phenotype and MMP activity in saphenous veins obtained before and after surgical manipulation. Surgical preparation of the veins significantly increased pro-MMP-1 expression by 2-fold and significantly reduced tissue inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected. Furthermore, caseinolytic and gelatinolytic activities measured by in situ zymography were dramatically elevated by injury. The expression of desmin and smoothelin was significantly decreased by injury, whereas vimentin expression was significantly increased. In addition, these changes in phenotype and MMP activity were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our data show that surgical preparative injury induces phenotypic modulation of a subpopulation of medial VSMCs to a synthetic phenotype and increases MMP activity. This may favor matrix degradation, VSMC migration, and the subsequent intimal thickening that leads to graft failure. Medial VSMCs exist in the normal blood vessel wall in the contractile (differentiated) phenotype. These have a "spindlelike" morphology, maintain vessel wall tone, and are rich in contractile and intermediate filament proteins (IFPs). It has been suggested that migrating and proliferating VSMCs have dedifferentiated to a synthetic phenotype, characterized by a reduction in contractile proteins and alterations in IFPs (see review by Owens 5 ). Recent studies illustrate that the amounts of the IFPs vimentin and desmin, the cytoskeleton-related protein smoothelin, and the contractile proteins ␣-smooth muscle (SM) actin, SM myosin heavy chain (SMMHC), and tropomyosin change when VSMCs shift from the contractile to the synthetic phenotype. [5][6][7] Mechanical injury to the blood vessel wall, particularly endothelial damage, is thought to trigger phenotypic modulation of medial VSMCs, shifting them toward the synthetic phenotype (see reviews by Thyberg and colleagues 8 -10 ). To enable VSMC migration, remodeling of the basement membrane and of the interstitial collagenous matrix that maintains VSMCs in a quiescent state must occur. 11 Mechanical injury of aortic explants 12 and isolated VSMCs 13 stimulates the production of extracellular matrix-degrading metalloproteinases (MMPs), which are mainly associated with VSMCs of the synthetic phenotype. 14,15 Injury of rat carotid arteries 16 and human saphenous veins 17 increases the expression of basement membrane-degrading MMP-2 and MMP-9. Furthermore, MMP inhibitors,12,[18][19][20] as well as gene transfer of the endogenous tissue inhibitors of MMPs (TIMPs), [21][22][23][24][25] have demonstrated the involvement of MMPs in injury-stimulated intimal thickening. Injury also...

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“…An alteration in matrix synthesis directly leads to increased collagen content in the hyperplastic neointima during the first week after injury resulting from balloon angioplasty [227]. In addition, AVGs that undergo this hyperplastic remodeling exhibit decreased compliance as compared to fresh veins [228], which can contribute to their failure [229,230].…”

Section: Remodelingmentioning

confidence: 99%

“…The degree of AVG distension is directly related to its mechanical properties, which, in turn, is related to patency rates according to Davies et al [229,230], who reported lower patency rates of less compliant AVGs in peripheral bypass surgery. This reduced patency has been largely attributed to compliance mismatch between the AVG and the native artery to which it is grafted [18,232,233].…”

Section: Changes In Mechanical Properties Of Vein Grafts Due To Artermentioning

confidence: 99%

In Situ Bioengineering of Arterial Vein Grafts

El-Kurdi

Morelli

Hong

et al. 2008

ASME 2008 Summer Bioengineering Conference, Parts a and B

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The autogenous saphenous vein remains the graft of choice for both coronary (500,000 annually in the US) and peripheral (80,000 annually) arterial bypass procedures. Failure of arterial vein grafts (AVGs) remains a major problem, and patients with failed grafts will die or require reoperation. Intimal hyperplasia (IH) accounts for 20% to 40% of all AVG failures. It is believed that this adverse pathological response by AVGs is largely due to their abrupt exposure to the significantly elevated circumferential wall stress (CWS) associated with the arterial system. We believe that if an AVG is given an ample opportunity to adapt and remodel to the stresses of its new environment, cellular injury may be reduced, thus limiting the initiating mechanisms of IH.The goal of this work was to develop a new mechanical conditioning paradigm, in the form of a peri-adventitially placed, biodegradable polymer wrap, to safely and functionally "arterialize" AVGs in situ. The polymer wrap was tuned so that as it degraded over a desired period of time, the mechanical support offered by it was reduced and the vein was exposed to gradually increasing levels of CWS in situ.To investigate the effects of mechanical conditioning on AVGs, we utilized both our well established, validated ex vivo vascular perfusion system (EVPS) as well as an appropriate preclinical animal model. The "engineering" component of this bioengineering study was to enhance our EVPS capabilities. Enhancements were made in the form of rigorous mathematical modeling, via subspace system identification, and automatic feedback control, via proportional iv integral and derivative control, of the arterial CWS and shear stress waveform generation capabilities of the EVPS. Pairs of freshly harvested porcine internal jugular veins (PIJVs) were perfused ex vivo under several biomechanical conditions. The acute hyperplastic response of PIJVs abruptly exposed to arterial hemodynamic conditions was compared to PIJVs perfused under normal venous conditions. In an attempt to attenuate this acute hyperplastic response, an ex vivo mechanical conditioning paradigm was imposed onto the PIJVs both via manual adjustment of EVPS parameters and via an adventitially placed tuned electrospun biodegradable polymer wrap. Early markers of IH were evaluated post-perfusion, and they included vascular smooth muscle cell apoptosis, proliferation, and phenotypic modulation. Quantification of these markers via immunohistochemical techniques provided the foundation for the final stage of this work. To assess the efficacy of the tuned electrospun biodegradable polymer wrap in attenuating the development of intimal hyperplasia in AVGs, a series of preclinical studies was performed in a pig model. PIJVs abruptly exposed to arterial levels of CWS showed a significant increase in apoptosis and in the number of synthetic smooth muscle cells, as well as a decrease in proliferation. Mechanical conditioning, via both manual adjustment of the EVPS parameters and placement of the biodegradable adventitial wra...

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Pre-bypass morphological changes in vein grafts

Cited by 50 publications

References 22 publications

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein

In Situ Bioengineering of Arterial Vein Grafts

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