-
[show abstract]
[hide abstract]
ABSTRACT: Intimal hyperplasia at the venous anastomosis of dialysis access grafts causes early failure, although increased flow inhibits intimal hyperplasia in arterial grafts and after vessel injury. We designed a sheep model to study this process.
Polytetrafluoroethylene (PTFE) grafts were placed in the necks of sheep from the carotid artery to the external jugular vein. Grafts were harvested after perfusion fixation at 4, 8, and 12 weeks and submitted for histologic and immunohistochemical examination, including morphometry of neointimal lesions.
The venous anastomoses developed thick neointima within the PTFE graft by 4 weeks. Lesions at the venous end were significantly thicker than those at the arterial end by 8 weeks (1.2 +/- 0.1 vs 0.38 +/- 0.05 mm, P <.02) and had greater cross-sectional area at both 4 (0.32 +/- 0.21 vs 3.6 +/- 0.8 mm(2), n = 7, P <.02) and 8 weeks (9.8 +/- 1.9 vs 1.1 +/- 0.7 mm(2), n = 7, P <.02). Only one of the four grafts (25%) in the 12-week group remained patent. Lesions were composed of smooth muscle cells, matrix, and thrombus of various ages. Cellular proliferation was prominent in neointima adjacent to thrombus and in granulation tissue surrounding the graft. Organizing thrombus contributed significantly to luminal narrowing.
The sheep model of dialysis access reliably produces venous stenosis within 4 weeks. Lesions develop in the absence of uremia, graft puncture, or dialysis, suggesting that these factors are not necessary for graft failure. The continued presence of thrombus and high rates of cellular proliferation suggest ongoing injury is an important cause of lesion formation. This model allows study of the cellular mechanisms of dialysis failure.
Journal of Vascular Surgery 11/1999; 30(4):744-51. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Columbia-Rambouillet cross-bred sheep were used to study the revascularization and ligamentization process of anterior cruciate ligament (ACL) reconstruction over a 6-month period using basic histology, immunohistochemistry, and electron microscopy. The reconstruction technique studied was a quadruple-hamstring, interference screw fixation technique. Further, these specimens, after retrieval at 6, 12, and 26 weeks, were compared with human arthroscopic 'second looks' and with 10 en bloc specimens obtained when a cruciate-sacrificing total knee replacement was performed. The study showed that, with this reconstruction technique, Sharpey's fibers were seen at 6 weeks in both sheep and human specimens. The intratunnel specimens showed proliferative chondrification, then ossification of the matrix. Intra-articular neovascularization, ligamentization, and junction ossification occurred. Myoblasts or smooth muscle cells appear to mediate the ligamentization as evidenced in electron microscopy by proliferate collagen manufacture. These myoblasts were seen in both the healing sheep and human second looks, but not seen in mature ACL grafts or in normal ACLs. At 6 months postoperatively, the sheep ACL reconstruction appeared clinically, histologically, and immunohistochemically indistinguishable from the normal sheep ACL. A correlation of this work with published animal studies in which biomechanical testing was performed and with human 'second looks' would imply that an ACL reconstruction may be vulnerable during this period of neovascularization and ligamentization.
Arthroscopy The Journal of Arthroscopic and Related Surgery 11/1998; 14(7):702-16. · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Thrombosis associated with central venous catheters is a significant cause of device failure, morbidity, and loss of access sites. We hypothesized that central vein thrombosis is caused by catheter injury to the vein wall and that it can be reduced by stabilizing the catheter tip. To test these hypotheses, we studied central vein catheters in a porcine model. Test catheters had a silicone-encased stainless steel loop at the indwelling end that contacted the vein wall and stabilized the catheter tip in the center of the vessel.
Sealed silicon elastic (Silastic) catheters (3.2 mm outer diameter) with and without a stabilizing loop were inserted via the external jugular vein into the superior vena cava just above the right atrium. Animals were killed at 1, 2, 4, and 8 weeks, and the vena cava was inspected for the presence of thrombus and entrapment of the catheter tip.
In control animals mural thrombus developed at the site of the catheter tip. This thrombus organized by invasion of macrophages and smooth muscle cells, eventually forming a lesion similar to intimal hyperplasia. Lesion cross-sectional area was significantly smaller in animals with loop catheters than in control animals at 2 weeks (1.2 +/- 1.3 vs 34.5 +/- 23.9 mm2; p = 0.05) and 4 weeks (2.8 +/- 0.3 vs 13.9 +/- 5.8 mm2; p < 0.05). By 8 weeks the vena cava was nearly occluded in most animals and the catheter tip was entrapped in this lesion in all cases. Test catheters eliminated the injury process for up to 8 weeks (p < 0.01, chi2 control vs loop catheter entrapment). Very little injury response was found where the loop contacted the vein wall, and the catheter tip was free of thrombus in all cases.
Mural thrombosis at the tip of indwelling central catheters is caused by chronic mechanical venous wall injury. Vessel injury and the resulting thrombosis can be prevented by a catheter modification that stabilizes the tip. Such a catheter may significantly reduce catheter malfunction and morbidity associated with these devices.
Journal of Vascular Surgery 07/1998; 28(1):59-65; discussion 65-6. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Polytetrafluoroethylene (PTFE) grafts placed into the arterial circulation of baboons for 8 weeks under high blood flow (HF) conditions develop a thin intima composed of smooth muscle cells (SMCs) and extracellular matrix beneath an endothelial monolayer. When these grafts are returned abruptly to normal flow (NF), they develop marked intimal thickening within 1 month. The mechanisms underlying this thickening are unclear. We studied the SMC response to altered flow by placing bilateral aortoiliac PTFE grafts into baboons with bilateral femoral arteriovenous fistulas. After 8 weeks, one fistula was closed, returning the graft flow on that side to NF. The opposite graft remained under HF conditions. Flow differences were monitored with duplex ultrasound (for all grafts: NF, 135 +/- 21 [mean +/- SEM] mL/min; HF, 507 +/- 35 mL/min; P < .001). Grafts were removed 2, 4, 7, 14, or 28 days later (five animals per group). Endothelial coverage, as assessed by scanning electron microscopy, was intact in each graft. Intimal area and SMC number increased progressively in NF grafts through 28 days (for area: NF, 3.0 +/- 0.3 mm2; HF, 0.6 +/- 0.2 mm2; P < .001; and for SMCs per cross section: NF, 11.8 +/- 1.1 x 10(3); HF, 2.6 +/- 1.0 x 10(3); P < .002). Intimal SMC proliferation (thymidine labeling) was increased significantly in NF grafts at 4 and 7 days (at 4 days: NF, 5.9 +/- 1.5%; HF, 1.4 +/- 0.6%; P < .05). Extracellular matrix accounted for an equal proportion of intimal mass in NF and HF grafts (percent matrix at 28 days: NF, 62.9 +/- 1.6%; HF, 63.7 +/- 4.7%; P = NS). We conclude that intimal thickening in this model of flow-induced vascular remodeling is due to increased SMC proliferation and accumulation of SMCs with a proportionate amount of extracellular matrix.
Circulation Research 01/1994; 74(1):14-23. · 9.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Healing baboon polytetrafluoroethylene grafts express PDGF mRNA in the neointima. Perfusates of graft segments also contain PDGF-like mitogenic activity. To extend these findings, we studied the expression and regional distribution of the PDGF protein isoforms and their receptors in this prosthetic graft model. By immunohistochemistry, as well as ELISA and Western blot analysis of tissue extracts, both PDGF-A and PDGF-B were identified in macrophages within the interstices of the synthetic material. In contrast, the neointima contained predominantly PDGF-A localized to the endothelial surface and the immediate subjacent smooth muscle cell layers. Tissue extracts of neointima and graft material were mitogenic for baboon aortic smooth muscle cells in culture; nearly all of this proliferative activity was blocked by a neutralizing anti-PDGF antibody. PDGF receptor beta-subunit mRNA and protein were easily detectable in the neointima and graft material. PDGF receptor alpha-subunit mRNA was also observed in the graft matrix and at lower levels in the neointima. This pattern of ligand and receptor expression further implicates locally produced PDGF as a regulator of neointimal smooth muscle cell growth in this model. The coexpression of ligand and receptor in the macrophage-rich matrix also suggests that PDGF may participate in the foreign body response.
Journal of Clinical Investigation 08/1993; 92(1):338-48. · 15.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In baboons, nonreinforced (unwrapped) 60 microns internodal distance polytetrafluoroethylene grafts form a complete endothelial lining within 2 weeks by capillary ingrowth through the wall. Smooth muscle cells then grow under the endothelium and proliferate to form a complete neointima. To determine if spontaneous endothelialization of these grafts can also occur in humans, 10 above-knee femoropopliteal grafts composed of equal lengths of 60 and 30 microns polytetrafluoroethylene were placed in eight patients. These grafts were reinforced (wrapped) for human use. Because biopsy of the grafts was not possible, endothelialization was assessed noninvasively by 111In-labeled platelet imaging 1 week and 3 months after surgery. There was no difference in indium uptake between 60 and 30 microns segments at either time. Histologic sections were available from 60 microns segments of two patients who underwent operation for graft thrombosis. Capillary ingrowth was seen in these grafts, but it rarely extended more than half the distance from the outside of the graft to the lumen. Smooth muscle cells were not seen on the flow surface, indicating that a neointima had not formed. These findings demonstrate that capillary ingrowth can occur in 60 microns grafts in humans but does not produce an endothelial lining. The failure to endothelialize is perhaps a result of inadequacy of angiogenesis in adult humans or retardation of capillary ingrowth by the reinforcing wrap.
Surgery 12/1992; 112(5):901-7. · 3.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study examined the accuracy of duplex ultrasound measurements of volume flow in a baboon model. Volume flow (Vf) through the external iliac artery was calculated from measurements of blood velocity averaged over several cardiac cycles (time-averaged velocity [TAV]) and vessel cross-sectional area (A) measured from the B-mode image: Vf = TAV x A. Fourteen anesthetized baboons were studied with a duplex scanner with a 7 MHz imaging transducer and 5 MHz pulsed Doppler. B-mode ultrasound measurements of external iliac artery diameters (2.5 +/- 0.2 mm) were used for calculation of cross-sectional area. Timed blood collections obtained through a cannula inserted into the common femoral artery and TAV measurements were obtained simultaneously during 6 to 15-second intervals. These measurements were repeated three to five times per animal with different flow rates each time. Flow rates ranged from 56 to 280 ml/min (170 +/- 54 ml/min). Average velocity was 55 +/- 17 cm/sec. There was no significant difference between the two methods of volume flow measurement (Student t test). Linear regression analysis revealed a high degree of correlation (r = 0.90, slope 0.95, and p = 0.0001). The absolute percentage error was 13% +/- 8%. Volume flow measured by duplex scanning correlates highly with timed blood collections. This method has potential application for the evaluation of diseased arteries and bypass grafts whose rates of flow and waveform patterns are similar to those of this experiment.
Journal of Vascular Surgery 11/1992; 16(4):520-6. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Smooth muscle cells (SMCs) in balloon-injured rat carotid artery express tissue-type plasminogen activator (t-PA) at a time when they are migrating from the media to the intima. Since heparin inhibits SMC migration and intimal thickening, we have examined the possibility that heparin might also inhibit t-PA expression. Heparin (nonanticoagulant fraction; molecular weight, approximately 6,000) was administered by continuous intravenous infusion (1.0 mg/kg per hour) to Sprague-Dawley rats subjected to balloon injury of the left common carotid artery. At various times up to 14 days after injury, plasminogen activator expression was analyzed by zymography, plasmin generation, enzyme-linked immunosorbent assay, Northern blotting, and in situ hybridization. This dose of heparin inhibited SMC accumulation at 14 days by 60%. Both urokinase plasminogen activator (u-PA) and t-PA activity increased in injured arteries and reached a maximum at 7 days. Heparin treatment decreased t-PA, but not u-PA, activity. Total t-PA protein was decreased by treatment with heparin but not chondroitin sulfate, and the decrease in t-PA protein was associated with decreased t-PA mRNA in the media. These results in the injured rat carotid artery agree with our earlier observations that heparin inhibits t-PA gene expression in cultured baboon aortic SMCs. They also provide support for the hypothesis that heparin interferes with the expression of certain proteases required for SMC migration and proliferation.
Circulation Research 07/1992; 70(6):1128-36. · 9.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intimal hyperplasia is a primary cause of failure after vascular reconstruction and may be affected by blood flow. We have studied the effects of increased blood flow on intimal hyperplasia in porous polytetrafluoroethylene grafts implanted in baboons. These grafts develop an endothelial lining by 2 weeks and neointimal thickening due to proliferation of underlying smooth muscle cells by 1 month. Creation of a distal arteriovenous fistula increased flow (from 230 +/- 35 to 785 +/- 101 ml/min, p less than 0.001) and mean shear (from 26 +/- 4 to 78 +/- 10 dynes/cm2, p less than 0.001) without causing a drop in pressure across the grafts. Fistula flow did not alter the pattern of endothelial coverage but did cause a marked reduction in the cross-sectional area of the neointima (from 2.60 +/- 0.52 to 0.42 +/- 0.07 mm2 at 3 months, p less than 0.01). Detailed morphometric analysis revealed an equivalent percentage decrease in smooth muscle cells and matrix content, suggesting that the primary effect of increased flow was to reduce smooth muscle cell number without affecting the amount of matrix produced by individual cells. The neointima remained sensitive to changes in flow at late times; ligation of the fistula after 2 months resulted in a rapid increase in neointimal thickness (from 0.60 +/- 0.03 mm2 after 2 months of fistula flow to 3.88 +/- 0.55 mm2 1 month after ligation of fistula, p less than 0.01). These results support the hypothesis that changes in blood flow affect the structure of diseased as well as normal vessels.
Circulation Research 01/1992; 69(6):1557-65. · 9.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a baboon graft model of arterial intimal thickening, smooth muscle cells (SMC) have been observed to proliferate underneath an intact monolayer of endothelium and in the absence of platelet adherence. Because platelets are not present and therefore cannot be a major source of growth stimulus, we have proposed that the vascular wall cells in the graft intima express mitogens and regulate SMC proliferation. To test this hypothesis, we assayed the grafts for mitogenic activity and expression of growth factor genes. Segments of healing graft and of normal artery, when perfused ex vivo, released mitogenic activity into the perfusate. The graft released more mitogen than the normal arterial segment, and some of the activity was inhibitable with an antibody to human platelet-derived growth factor (PDGF). In addition, Northern analysis of total RNA demonstrated higher expression of PDGF-A chain mRNA in the graft intima compared to normal artery. PDGF-B chain mRNA was barely detectable in both tissues. PDGF mRNA levels within the graft interstices were not measured. In situ hybridization of 7.5- or 12-wk grafts indicated that some luminal endothelial cells and adjacent intimal SMC contained PDGF-A chain mRNA. By thymidine autoradiography, intimal SMC were observed to be proliferating in the inner third of the intima. These data demonstrate a difference in the pattern of PDGF transcript expression and luminal perfusate activity in graft as compared with control arteries. The association of intimal smooth muscle cell proliferation with intimal PDGF mRNA expression and release of PDGF-like protein supports the hypothesis that factors from cells that have grown into the graft or populated its surface rather than platelets may regulate intimal smooth muscle cell proliferation in this model.
Journal of Clinical Investigation 03/1991; 87(2):406-14. · 15.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study examined long-term changes in the morphology and cellular kinetics of rabbit vein grafts transplanted into the carotid artery. Six grafts were studied 1 year after implantation. Although the circumference and thickness of the wall were not different than at 12 weeks, degenerative changes occurred. The endothelial lining of the graft appeared intact, but large segments of the graft surface no longer excluded Evans blue dye, suggesting increased permeability. Collections of red blood cells were noted within the intima. Several grafts had extensive subendothelial fibrin deposits, often associated with foam cells, and evidence of previous hemorrhage, but these changes did not stimulate significant smooth muscle cell proliferation. Increased permeability with entrance of proteins and erythrocytes into the intima may result from increased wall tension or from low shear rates at the wall. Similar changes may lead to atherosclerosis in human vein grafts at late times.
The American Journal of Surgery 10/1990; 160(3):257-61. · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The importance of porosity in synthetic arterial graft healing has not been adequately defined. To determine the effect of porosity on graft healing, we measured the extent of cellular response at late times in 4 mm internal diameter polytetrafluoroethylene grafts of varying porosity (between 10 and 90 microns internodal distance) inserted into the arterial system of baboons. After 1 and 3 months the grafts were retrieved and examined for endothelial coverage, intimal thickening, and endothelial cell and smooth muscle cell proliferation. The pattern of intimal healing with endothelial cells and smooth muscle cells was only related to porosity in the sense that there was an abrupt switch in the pattern of healing as porosity was increased from 30 to 60 microns. In low porosity grafts (10 and 30 microns internodal distances) endothelial coverage of the luminal surface was incomplete and, along with intimal thickening, was limited to graft near the anastomosis. In high porosity grafts (60 and 90 microns internodal distances) luminal endothelial coverage was complete, and intimal thickening was uniformly distributed throughout the graft. The highest porosity graft studied (90 microns) developed areas of focal loss of endothelial cells at late time periods. In this limited series there does appear to be an optimal porosity for polytetrafluoroethylene grafts near 60 microns, since 10 and 30 micron grafts fail to achieve luminal endothelial cell coverage, and 90 micron grafts exhibit instability of the intima with focal endothelial cell loss.
Journal of Vascular Surgery 07/1990; 11(6):838-44; discussion 845. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In previous experiments vein graft wall thickening stopped when the ratio of lumen radius to wall thickness equaled that of a normal artery. This led us to postulate that wall stress, which this ratio determines, regulates wall structure. To test this hypothesis we studied the effect of decreasing lumen radius and acutely diminishing wall stress with a rigid, external support. Jugular vein grafts were interposed into the carotid artery of rabbits. The proximal half of the grafts was wrapped with a polytetrafluoroethylene graft. Twelve veins received a tight wrap (2.5 or 3 mm diameter) that decreased the graft diameter, and four received a loose wrap (5 mm diameter) that did not. These grafts were fixed by perfusion after 1 day, 11 days, or 12 weeks. Wall thickness was slightly less in all tight-wrap segments. Total cross-sectional wall area, smooth muscle cell volume, and matrix deposition were significantly reduced in tight-wrap segments. These differences were greatest at 11 days. The observation that narrowing and external support of these vein grafts causes reduction of wall area supports the hypothesis that increased wall stress might be an important stimulus for wall thickening.
Journal of Vascular Surgery 03/1989; 9(2):277-85. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In earlier studies, we have shown that porous (60 micron internodal distance) PTFE grafts develop a complete endothelial layer 2 weeks after being implanted in baboons. Subsequently, the intima of the graft thickens on account of SMC proliferation only where an overlying endothelial layer is present. SMCs in normal endothelialized artery proximal and distal to the graft show no detectable proliferation. The purpose of this study was to investigate the possibility that growth factors released from the graft endothelium or SMCs regulate SMC proliferation. PTFE grafts (4 mm I.D., 60 micron internodal distance) were placed in the aortoiliac circulation of baboons and removed at 2 weeks. The grafts were perfused ex vivo with tissue culture medium (Ham's F12 + 25 mmol/L HEPES and 2% calf plasma-derived serum) at 2.5 ml/hr for 5 hours. Perfused native carotid, aorta, and femoral arteries served as controls. After this period of perfusion, graft and arterial endothelium was intact as shown by scanning electron microscopy. The mitogenic activity (thymidine incorporation) of the perfusates was measured in an assay with quiescent 3T3 cells and baboon aortic SMCs and corrected for the surface area of the perfused vessels. These studies demonstrated markedly increased mitogenic activity in the perfusates of grafts compared with perfusates of native vessels. These results provide support for the hypothesis that the vascular wall cells in healing grafts can produce factors that regulate smooth muscle cell growth.
Journal of Vascular Surgery 05/1988; 7(4):606-10. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In previous baboon studies we have shown that porous (60 micron mean internodal distance) polytetrafluoroethylene (PTFE) grafts heal by ingrowth of endothelium and smooth muscle cells from the adjacent artery and from capillaries penetrating through the interstices of the graft. However, porous grafts (principally made of Dacron) in humans do not heal. This has been attributed to a wound healing deficiency in humans; however, it might be due to an inhibitory effect of the Dacron itself. To examine the latter possibility, we undertook this study to compare the healing of 4 mm internal diameter porous Dacron grafts (USCI, Sauvage Filamentous Knitted) with that of Gore-Tex 60 micron PTFE grafts in baboons (the latter graft not available for clinical use). The grafts were harvested at 2, 4, and 12 weeks and assessed for (1) percentage of endothelial coverage, (2) endothelial cell (EC) proliferation (thymidine labeling index), (3) intimal area, and (4) smooth muscle cell (SMC) proliferation (thymidine labeling index). The PTFE grafts at all three time points were fully covered, whereas only one of five Dacron grafts was completely covered at 12 weeks. The intima of the PTFE grafts consisted of ECs and SMCs, whereas that of the Dacron grafts contained ECs and SMCs as well as focal accumulations of thrombus. The intimal cross-sectional areas in the Dacron grafts (3.0 +/- 1.2 mm2) were significantly greater than in the PTFE grafts (0.8 +/- 0.6 mm2) at 4 weeks; there was no difference at 12 weeks (Dacron, 2.6 +/- 2.3 mm2 and PTFE, 3.0 +/- 2.5 mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Vascular Surgery 12/1987; 6(5):429-36. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Synthetic arterial grafts fail because of thrombosis. Rapid endothelial coverage would be expected to generate a minimally thrombogenic surface and reduce the rate of failure. We investigated the possibility that such a lining could be established by transmural capillary ingrowth in polytetrafluoroethylene (30 or 60 micron internodal distance) and Dacron baboon aortoiliac grafts of 4 mm in diameter and 5 to 7 cm in length. All grafts demonstrated endothelial ingrowth from the cut edges of adjacent artery. The central portions of the 30 micron polytetrafluoroethylene grafts were still not healed at 3 months. Two of six Dacron grafts were healed 1 month postoperatively and all were healed at 3 months, whereas all 60 micron polytetrafluoroethylene grafts were healed 2 weeks postoperatively. At early follow-up, islands of endothelium were seen in the middle of the 60 micron polytetrafluoroethylene and Dacron grafts. These observations support the concept that transmural migration of capillaries can provide multiple sources of endothelium and early endothelial coverage of porous synthetic arterial grafts. This response is affected by the porosity and possibly the thrombogenicity of the graft material.
The American Journal of Surgery 06/1987; 153(5):501-4. · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a previous study of arterial bypass grafts (4 mm polytetrafluoroethylene [PTFE]) in baboons we observed that endothelial and smooth muscle cells (SMCs) formed the neointima and were derived from the cut edges of adjacent artery. The purpose of this study was to determine at late times whether endothelial cells would continue to migrate and to proliferate to cover the graft surface and whether the underlying proliferating SMCs would produce a progressively thickened intima, graft stenosis, and eventual thrombosis. At 6 and 12 months after grafts were placed, endothelial coverage by ingrowth from the anastomoses was more advanced than at 3 months, and by 12 months 60% of grafts (7 to 9 cm in length) were covered. Endothelial cells proliferated in association with the growing edge and focally in other regions. Underlying SMCs proliferated in the region of the growing edge of the endothelial cells and also at anastomoses. Intimal cross-sectional area was greatest at anastomoses and at late times was principally due to an increase in connective tissue; actual SMC mass remained constant after 3 months. These results demonstrated slow but progressive healing of the grafts by ingrowth of endothelium. There was also an increased turnover rate of SMCs and endothelial cells in established intima at late times, which might be the consequence of chronic endothelial injury. This condition represents a stable state since it does not produce further intimal thickening and accumulation of SMCs and does not lead to a high rate of thrombosis.
Journal of Vascular Surgery 07/1986; 3(6):877-84. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The cellular lining of 4-mm polytetrafluoroethylene (PTFE) arterial bypass grafts of differing porosity implanted into baboons for a period of 3 months was investigated. Endothelial outgrowth onto the less porous (30-mu) PTFE grafts varied from approximately 1 to 3 cm, and 75% of the grafts were totally reendothelialized within 3 months. These luminal cells stained positive for Factor VIII.R.Ag. The endothelial replication in the healed grafts was significantly elevated as compared with that observed in adjacent arteries. By electron microscopy, no breaks were detected in the integrity of the endothelium and no increase in indium activity over the graft was recorded after injection of 111In-labeled platelets. To ensure that the increased cell replication was not related to regrowth, a more porous PTFE graft (60 mu) was implanted which reendothelialized within 2 weeks. Three months after implantation, the replication rate of endothelium in the graft was still significantly increased. The authors concluded that this increased replication represented a desquamating nondenuding injury and that flow characteristics along the graft might be responsible.
American Journal Of Pathology 07/1986; 123(3):432-9. · 4.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial coverage of an exposed synthetic vascular graft surface limits thrombosis and may improve long-term graft performance. In most types of synthetic graft, luminal endothelium is derived from the cut edges of adjacent artery. In this study the authors investigated the possibility that endothelial coverage could also be obtained by ingrowth of capillaries from the outside of the graft. Porous 4-mm polytetrafluorethylene (PTFE; 60 mu internodal distance) grafts were inserted into the aortoiliac circulation of baboons and were retrieved at intervals of up to 12 weeks. Between 1 and 2 weeks after surgery a continuous sheet of cells began to appear on the surface along the entire graft. These cells stained for Factor VIII related antigen, exhibited endothelial morphology by scanning electron microscopy, were associated with capillary orifices at the luminal surface, and covered the entire graft by 4 weeks. Transmural capillaries were observed to connect the graft lumen to extravascular granulation tissue. Despite full coverage of the graft, endothelial cells continued to exhibit increased proliferation (thymidine labeling) at 12 weeks. Smooth muscle cells (pericytes) accompanied capillary endothelium into the graft lumen, exhibited vascular smooth-muscle-specific immunostaining, and proliferated under the luminal endothelium to form intima. These results indicate that under some circumstances capillary endothelium and smooth muscle cells can function in the same manner as large vessel endothelium and smooth muscle and can provide rapid coverage of porous synthetic graft surfaces in contact with the arterial circulation.
American Journal Of Pathology 06/1986; 123(2):220-30. · 4.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Human coronary saphenous vein bypass grafts develop atherosclerosis more readily than do grafts made of internal mammary artery. The reasons for this increased susceptibility, particularly in the presence of hyperlipidemia, are not known. In this study in rabbits, we investigated the possibility that the increased susceptibility might be attributed to increased smooth muscle proliferation and foam cell accumulation in vein grafts compared to native artery. Hypercholesterolemic and control rabbits underwent placement of jugular vein grafts in the carotid artery. Dietary cholesterol content was adjusted to maintain serum cholesterol levels of 200 to 600 mg/dl in the fat-fed rabbits. The vein graft intimal thickness in hypercholesterolemic rabbits was greater than in normolipemic rabbits at 3 and 6 months after implant. The increased thickness in the hypercholesterolemic group was largely accounted for by an accumulation of lipid-laden macrophages. Medial thicknesses increased during the first month, remained constant at later times, and were similar in control and hypercholesterolemic animals. In both groups, endothelial and smooth muscle cell proliferation (thymidine labeling) increased immediately after graft implantation and declined at 3 and 6 months. No incremental mitogenic stimulus could be attributed to the hypercholesterolemia. In immunohistochemical preparations, the large foam cells were noted to be macrophages, and the intimal proliferating cells, to be smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriosclerosis (Dallas, Tex.) 9(3):374-9.
