The role of platelet-derived growth factor in intraluminal stented graft healing.

BACKGROUND: Intraluminally placed polytetrafluoroethylene grafts are associated with enhanced graft endothelialization and diminished intimal hyperplasia when compared with interposition grafts. This study determined the role of platelet-derived growth factor in intraluminal graft healing. STUDY DESIGN: Thirty dogs underwent infrarenal abdominal aorta polytetrafluoroethylene interposition (control, n = 15) or intraluminal stented (n = 15) grafting. Grafts were explanted at 1, 3, and 6 weeks. The percent of graft area endothelialization and intima to media height ratios were calculated. By using protein electrophoresis and the Western blot technique, platelet-derived growth factor, identified by immunolabeling with anti-platelet-derived growth factor antibody, was isolated from proximal, mid-, and distal graft regions and was quantified using densitometry. RESULTS: Graft area endothelialization was 0 +/- 3.3 percent, 2.3 +/- 3.3 percent, and 19.0 +/- 3.3 percent for 1-, 3-, and 6-week controls; and 4.7 +/- 3.7 percent, 30.5 +/- 3.3 percent, and 86.8 +/- 3.3 percent for 1-, 3-, and 6-week stented grafts. Endothelialization was greater in stented grafts at 3 and 6 weeks (p < .01). Proximal anastomosis intima to media height ratios were 1.61 +/- 0.15, 1.54 +/- 0.14, and 1.48 +/- 0.15 for 1-, 3-, and 6-week control grafts, and 0.42 +/- 0.18, 0.41 +/- 0.15, and 0.47 +/- 0.14 for 1-, 3-, and 6-week stented grafts. Similar intima to media height ratio values were present at the distal anastomosis. Lower intima to media height ratios were observed in all stented grafts (p < .01). The platelet-derived growth factor content at 1-, 3-, and 6-weeks was lower in all stented grafts when compared with controls. The content of platelet-derived growth factor was greatest in 3-week controls, with a significant difference noted in the mid-graft region (p < .05). The content of platelet-derived growth factor remained stable in all stented graft regions over 6 weeks. An inverse correlation between stented graft platelet-derived growth factor content and endothelialization (r = -0.43) and a positive correlation with proximal anastomotic intimal hyperplasia (r = 0.73) were identified. CONCLUSIONS: Lower platelet-derived growth factor content is associated with decreased intimal hyperplasia and improved healing in intra-arterial polytetrafluoroethylene grafts.

Effect of intra-arterial environment on endothelialization and basement membrane organization in polytetrafluoroethylene grafts.

PURPOSE: To determine if a complete intra-arterial environment affects endothelialization rate and basement membrane organization in polytetrafluoroethylene (PTFE) grafts. METHOD: Thirty dogs underwent either infrarenal abdominal aorta PTFE interposition (12) or intraluminal stented (18) grafting. Grafts were explanted at 4 and 8 weeks and rate of endothelial ingrowth calculated. Endothelial cells were identified and basement membrane organization assessed using antibodies against endothelial cell-specific surface antigen CD31, type IV collagen, and laminin. RESULTS: Endothelialization rates, expressed as percent graft surface area coverage per week, were 3.7% +/- 0.62% (4-week control), 12.9% +/- 0.58% (4-week stented), 4.2% +/- 0.62% (8-week control), and 10.0% +/- 0.54% per week (8-week stented grafts). Endothelial repaving rates were constant for control and increased in all stented grafts (P <0.01). At 4 weeks, laminin was identified in all control (6 of 6) and no stented grafts. Staining was confined to the 20% of the hyperplastic intimal area immediately below the endothelium. At 4 weeks, type IV collagen was present throughout the entire hyperplastic intima in control specimens but was confined to a discrete subendothelial zone in stented grafts. By 8 weeks, type IV collagen became concentrated in the luminal one third of the intima in control grafts. CONCLUSION: Intra-arterial graft location is associated with early formation of an organized basement membrane and accelerated endothelialization in PTFE grafts.

Effect of balloon-expandable and self-expanding stent fixation on endoluminal polytetrafluoroethylene graft healing.

PURPOSE: To investigate the effect of stent design and deployment mechanism on endoluminal graft healing. METHOD: Twenty dogs underwent infrarenal abdominal aorta polytetrafluoroethylene (PTFE) interposition (6) or intraluminal stented grafting using either a balloon expandable (BE, n = 8) or self-expanding (SE, n = 6) stent design. Grafts were removed at 8 weeks. Length of endothelial ingrowth and intima to media height ratios (IMHR) were calculated. Perianastomotic smooth muscle (Actin+), macrophage (CD44+), proliferating (PCNA+), and platelet-derived growth factor (PDGF+) cell content were determined. RESULTS: Mean endothelial ingrowth was 1.10 +/- 0.15 cm (control), 1.88 +/- 0.13 cm (BESG), and 2.16 +/- 0.18 cm (SESG) proximally; and 0.94 +/- 0.12, 2.11 +/- 0.11 cm, and 2.16 +/- 0.15 cm, respectively, at the distal anastomosis. Endothelial ingrowth was greater in all stented grafts (P <0.001). Mean IMHRs were 1.42 +/- 0.16 (control), 0.50 +/- 0.14 (BESG), and 0.77 +/- 0.2 (SESG) proximally; and 0.84 +/- 0.1, 0.42 +/- 0.09, and 0.77 +/- 0.12 (SESG) distally. Lower IMHRs were observed in all stented graft regions (P <0.05) except the distal anastomosis of SESG. The PDGF+ and PCNA+ cell content was decreased, and Actin+ cell content was increased in all stented grafts (P <0.05). CONCLUSION: Intraluminal location enhances endothelialization and attenuates intimal thickening in PTFE grafts. The enhanced healing of intraluminal stented grafts is irrespective of the type of stent or deployment mechanism used.

Infrainguinal arterial reconstructions in patients with aortoiliac occlusive disease: the influence of iliac stenting.

OBJECTIVE: Iliac artery angioplasty (IAA) is an effective adjunct when combined with infrainguinal arterial reconstructions (IARs) in appropriate patients with multilevel occlusive disease. However, the effect of iliac artery stenting (IAS) on the outcome of patients undergoing distal bypass procedures is not defined. The purpose of this study was to estimate the influence of previous IAS for iliac occlusive disease on the outcome of IARs, compared with those after IAA alone or aortofemoral bypass grafting procedures (AFBs). METHODS: During a 5-year period (1995-2000), 105 patients with previous intervention for iliac occlusive disease underwent 120 IARs. The criteria prepared by the Ad Hoc Committee on Reporting Standards (Society for Vascular Surgery/International Society for Cardiovascular Surgery) were followed to define the variables. The TransAtlantic Inter-Society Consensus classification was used to characterize the type of iliac lesions. Univariate (Kaplan-Meier) and multivariate analyses (Cox proportional hazards model) were used to determine the association between preoperative variables and cumulative primary patency. RESULTS: Forty-five IARs were performed in patients with an earlier IAS repair, 33 in patients with an earlier IAA repair, and 42 in patients with an earlier AFB repair. There were not significant differences between patients in the IAS and IAA groups, except for a more frequent use of polytetrafluoroethylene grafts for IARs in the IAS group (40% vs 15%; chi(2) test, P = .03). The 5-year primary patency rate for IARs was 68% in the IAS group, 46% in the IAA group, and 61% in the AFB group. Univariate analyses revealed that primary patency rates for IARs in patients with previous IAS were significantly higher than those in the IAA group (Kaplan-Meier, log-rank test, P = .02). Previous IAA repair was associated with a two-fold increased risk of IAR graft failure (relative risk, 2.2; 95% CI, 1.1-4.8; P = .04). CONCLUSIONS: IARs in patients with previous IAS have significantly improved graft patency, compared with those in patients with previous IAA alone. Such graft patency for IAR after IAS is similar to that obtained after AFB repair.

Effect of endoluminal PTFE graft placement on cell proliferation, PDGF secretion, and intimal hyperplasia.

To determine the effects of intraluminal placement on peri-anastomotic intimal hyperplasia and platelet derived growth factor (PDGF) secretion in polytetrafluoroethylene (PTFE) grafts. Infrarenal aortic PTFE grafts were placed in 30 dogs as either interposition (n = 12) or intraluminal stented (n = 18) grafts. Grafts were explanted at 4 and 8 weeks. At each anastomosis, intima to media height ratios (IMHR) were calculated, and smooth muscle (Actin), proliferating (PCNA), and PDGF secreting cell content determined using cell-specific immunohistochemical stains. At the proximal anastomosis, control and stented graft IMHRs were 1.01 +/- 0.16 vs 0.59 +/- 0.18 in 4-week and 1.42 +/- 0.16 vs 0.50 +/- 0.14 in 8-week specimens. Similar IMHR values were present for the distal anastomosis. Peri-anastomotic PCNA cell counts were greater in control grafts at both 4 and 8 weeks. Stented grafts were associated with diminished IMHR and PCNA+ content at both 4 and 8 weeks (P < 0.05). PDGF+ content was similar among control and stented grafts at 4 weeks, while lower in stented grafts at 8 weeks (P < 0.05). At the distal anastomosis, a correlation between PDGF secretion and Actin+ cell content was observed in control grafts at 4 (r = 0.74) and 8 (r = -0.56) weeks. Cell proliferation was associated with PDGF content in 4-week intraluminal and 8-week control grafts (P < 0.05). Changes in IMHR were not the result of differential PDGF secretion. Intraluminal location attenuates intimal hyperplasia in PTFE grafts. The reduced intimal hyperplasia and improved healing of endoluminal grafts could not be attributed to lower PDGF content alone.

Influence of hormone replacement therapy on graft patency after femoropopliteal bypass grafting.

OBJECTIVE: Thromboembolic events are more frequent in women with established cardiovascular disease who are receiving hormone replacement therapy (HRT). The effect of HRT on the outcome of women undergoing infrainguinal bypass grafting is unknown. The purpose of this study was to estimate the influence of risk factors, in particular HRT, on the outcome of women undergoing femoropopliteal bypass grafting. METHODS: During a 5-year period (between 1993 and 1998), 131 femoropopliteal bypass graft procedures were performed in 106 women. The criteria prepared by the Ad Hoc Committee on Reporting Standards (Society for Vascular Surgery/North American Chapter of the International Society for Cardiovascular Surgery) were followed. Both univariate (Kaplan-Meier method) and multivariate analyses (Cox proportional hazards model) were used to determine the association among preoperative variables, graft patency, limb salvage, and survival. RESULTS: The average age of the patients was 66.4 years; 26% of the patients were receiving HRT. Indications for femoropopliteal bypass grafting were limb salvage (80%) and disabling claudication (20%). Autogenous vein was used in 48% of procedures, polytetrafluoroethylene (PTFE) in 49%, and PTFE-vein composite grafts in 3%. Distal popliteal anastomosis was above the knee in 52% and below the knee in 48%. Overall primary patency rate was 81% at 1 year, 65% at 3 years, and 56% at 5 years. Primary patency rates at 1, 3, and 5 years were 75%, 45%, and 23%, respectively, for HRT users and 84%, 72%, and 65%, respectively, for nonusers of HRT. Overall, cumulative 1- and 5-year limb salvage results were 96% and 92%, respectively, and long-term survival at 1, 3, and 5 years was 96%, 86% and 74%, respectively. With univariate and Cox regression analyses, HRT was identified as the only independent predictor of reduced primary graft patency (Kaplan-Meier method, log-rank test, P =.004; relative risk, 2.5; 95% CI, 1.3-4.8). Women receiving HRT who underwent a procedure with PTFE had the lowest primary graft patency rates (relative risk, 3.4; 95% CI, 1. 5-7.8; P =.006). CONCLUSIONS: Women undergoing femoropopliteal bypass graft procedures who are receiving HRT have significantly reduced primary graft patency rates. The risk of graft failure increases when prosthetic materials are used.

Healing characteristics of intraarterial stent grafts in an injured artery model.

Previous investigations reveal in the absence of endothelial cell (EC) injury, intraarterial polytetrafluoroethylene (PTFE) stent graft (SG) exhibit greater EC repaving than PTFE interposition grafts (CG). The investigation evaluated EC repaving of SG compared to CG after balloon injury. Twenty adult dogs underwent SG (n = 10) or CG (n = 10) placement in the infrarenal aorta after balloon injury with harvest at 1 and 6 weeks. Endothelial repaving, intima-to-media height ratios (IMHR), and inflammatory stains were performed. Endothelial repaving was greater in 6-week SG compared to CG (51% +/- 5.0 versus 10% +/- 5.0, p < or = 0.05). IMHR was less in 6-week SG compared to CG at the proximal (1.22 +/- 0.16 versus 1.82 +/- 0.16, p < or = 0.05) and distal anastomosis (0.81 +/- 0.25 versus 1.33 +/- 0.25, p < or = 0.05). Smooth muscle cell (SMC) alpha-actin was greater in 1-week SG compared to CG at the distal anastomosis (121.5 +/- 7.2 versus 94.0 +/- 7.2, p < or = 0.05). Proliferating cell nuclear antigen (PCNA) was less in 6-week SG compared to CG at the proximal (5.6 +/- 1.4 versus 9.4 +/- 1.1, p < or = 0.05) and distal anastomosis (3.8 +/- 0.6 versus 11.2 +/- 1.1, p < or = 0.05). Macrophage CD-44 was less in 6-week SG compared to CG at the proximal (10.4 +/- 1.6 versus 32.6 +/- 3.6, p < or = 0.05) and distal anastomosis (8.6 +/- 0.9 versus 35.6 +/- 3.6, p < or = 0.05). Intraarterial SG placed after balloon injury exhibited significantly greater endothelialization and less intimal hyperplasia when compared to CG.

Effect of retroviral transduction of canine microvascular endothelial cells on beta(1) integrin subunit expression and cell retention to PTFE grafts.

This study evaluated the effect of retroviral transduction on canine microvascular endothelial cell (CMVEC) detachment from fibrin glue coated expanded polytetrafluoroethylene (ePTFE) graft material. CMVEC were isolated from adipose tissue by fluorescent activated cell sorting (FACS). Three treatment groups were evaluated: G-I, transduced CMVEC, selected in antibiotic G418 for 10 days (n=5); G-II, CMVEC selected in G418 and recovered from selection for 4 days (n=5); and G-III, control group of naive CMVEC (n=6). (3)H-thymidine labeled endothelial cells were seeded on fibrin glue coated four-mm diameter PTFE. Grafts were exposed to physiologic shear stresses of 16 dyn/cm(2). Cell detachment was determined by (3)H-thymidine counts in the circuit effluent. beta(1) integrin subunit expression was measured by flow cytometry. After 2 hours of flow exposure, G-I and G-II demonstrated significantly greater cell detachment rates compared with the control seeded grafts. Median peak channel beta(1) integrin subunit value for G-III CMVEC was 2311+/-481.7 vs. 31.5+/-4.51 and 26.3+/-2.0 in the transduced cell groups (p=0.00043). Low beta(1) integrin expression correlated with flow induced high detachment rates of retrovirally-transduced CMVEC.