Development of infection resistant polyurethane biomaterials using textile dyeing technology.

Infection is a major complication when using biomaterials such as polyurethane in the clinical setting. The purpose of this study was to develop a novel infection resistant polyurethane biomaterial using textile dyeing technology. This procedure results in incorporation of the antibiotic into the polymer, resulting in a slow, sustained release of antibiotic from the material over time, without the use of exogenous binder agents. Polycarbonate based urethanes were synthesized that contained either a non-ionic (bdPU) or anionic (cPU) chain extender within the polymer backbone and cast into films. The fluoroquinolone antibiotic ciprofloxacin (Cipro) was applied to bdPU and cPU using textile dyeing technology, with Cipro uptake determined by absorbance reduction of the "dyebath." These dyed bdPU/cPU samples were then evaluated for prolonged Cipro release and antimicrobial activity by means of spectrophotometric and zone of inhibition assays, respectively. Cipro release and antimicrobial activity by dyed cPU segments that were aggressively washed persisted over 9 days, compared with dyed bdPU and dipped cPU control segments that lasted < 24 hours. Dyed cPU segments, which remained in a static wash solution, maintained antimicrobial activity for 11 days (length of study), whereas controls again lost antimicrobial activity within 24 hours. Thus, application of Cipro to the cPU polymer by means of dyeing technology results in a slow sustained release of antibiotic with persistent bacteriocidal properties over extended periods of time.

Altered ubiquitin/proteasome expression in anastomotic intimal hyperplasia.

OBJECTIVE: Anastomotic intimal hyperplasia remains a leading mechanism of prosthetic arterial graft failure. Recent studies using messenger RNA differential display have demonstrated altered proteasome gene expression at the anastomoses in an expanded polytetrafluoroethylene canine carotid model. However, this technique is technically limited because of a paucity of available hyperplastic tissue at early time periods after arterial injury. Microarray gene chip technology offers a new and sensitive technique to assay early gene expression, requiring far less tissue for analysis. The purpose of this study was to screen for altered proteasome gene expression at 48 hours and 14 days after prosthetic arterial grafting. METHODS: Expanded polytetrafluoroethylene grafts (6-mm diameter, n = 9) were implanted into 25-kg mongrel dogs. The normal intervening carotid artery was used as control. At 48 hours and 14 days, RNA was extracted from the perianastomotic tissue and compared with RNA from the control carotid. Messenger RNA was then hybridized to microarray genomes screening for differential gene expression. RESULTS: Two 26S proteasome genes and five ubiquitin pathway genes were significantly underexpressed at 48 hours, among several hundred significantly expressed clones. The two 26S proteasome genes were 26S proteasomal subunit p55 (0.26), and 26S proteasomal subunit p40.5 (0.13). The underexpressed ubiquitin genes included ubiquitin (0.31), Nedd-4-like ubiquitin-protein ligase (0.30), ubiquitin conjugating enzyme UbcH2 (0.25), putative ubiquitin C-terminal hydrolase UHX1 (0.11), and ubiquitin-conjugating enzyme UbcH7 (0.12). At 14 days, six ubiquitin genes were underexpressed, and 17 26S proteasome genes were significantly downregulated. CONCLUSIONS: This study shows decreased expression of the ubiquitin/proteasome pathway 48 hours after graft implantation and similar diminished expression patterns after 14 days. This early and sustained underexpression after arterial bypass may lead to altered cell cycle control and matrix protein signaling, contributing to the unregulated proliferation of smooth muscle cells and extracellular matrix in anastomotic intimal hyperplasia after prosthetic arterial grafting.

Apolipoprotein J inhibits the migration, adhesion, and proliferation of vascular smooth muscle cells.

PURPOSE: Apolipoprotein J (ApoJ) is expressed during tissue injury and remodeling and has been implicated in vascular smooth muscle cell (VSMC) differentiation. Recently, the gene for ApoJ was identified as upregulated in distal anastomotic intimal hyperplasia after prosthetic arterial grafting. In this study we investigate the effect of ApoJ on VSMC migration, adhesion, proliferation, and gene expression. METHODS: To study the effect of ApoJ on cell migration, we used a microchemotaxis chamber with an intervening 8-microm pore semipermeable polycarbonate membrane. Assays were performed with ApoJ alone (1-50 microg/mL) or in combination with platelet-derived growth factor homodimer bb (PDGF-bb; 10 ng/mL) or 2% fetal bovine serum (FBS; n = 8) in the lower wells. The influence of extracellular matrix interactions on ApoJ and chemotaxis was studied in a similar way, except membranes were collagen coated. Furthermore, cells were exposed to ApoJ 15 minutes before or after seeding on the coated membrane (n = 10). The influence of ApoJ on cell adhesion to collagen was assessed with cell exposure to ApoJ 15 minutes before or after seeding on a collagen-coated membrane (n = 10). Migration and adhesion were quantified by counting the number of cells per three independent high-power fields with light microscopy. The effect of ApoJ in 0.4% FBS with or without PDGF-bb on VSMC proliferation (n = 12) was assessed by means of [Methyl-(3)H] thymidine incorporation. The transcriptional profile of VSMCs in 2% FBS exposed to ApoJ and a control for 24 hours was analyzed with an oligonucleotide microarray containing 12,560 genes. RESULTS: ApoJ alone was not chemotactic for VSMCs. Without collagen, ApoJ decreased the migration of VSMCs toward 2% FBS by 96% or more starting at 10 microg/mL (P < .05) and toward PDGF-bb by 60.9% or more starting at 25 microg/mL (P < .05) compared with the control. When collagen was introduced, ApoJ (25 microg/mL) decreased migration toward 2% FBS by 64% (P < .01) and toward PDGF-bb by 67.5% (P < .01) and decreased adhesion by 26.8% (P < .01) only when VSMCs in solution were exposed to ApoJ before placement on collagen. ApoJ did not induce VSMC proliferation. ApoJ alone decreased VSMC thymidine incorporation by 41.1% at 25 microg/mL (P < .05). ApoJ decreased thymidine incorporation of PDGF-bb stimulated VSMCs by 42.8% at 50 microg/mL (P < .05). Interleukin-8 and endothelin-1 were demonstrated by means of the microarray to be differentially expressed more than twofold in VSMCs that were exposed to ApoJ. CONCLUSION: ApoJ is a potent inhibitor of VSMC migration, adhesion, and proliferation. Its genetic targets are linked to cell senescence and differentiation. Therefore, ApoJ may play a role, in part, in modulating the VSMC response to injury.

Apolipoprotein J inhibits the migration and adhesion of endothelial cells.

BACKGROUND: Apolipoprotein J (ApoJ) is expressed after vascular injury and remodeling and may inhibit endothelial cell activation in the vascular wall. Recently, ApoJ was identified as upregulated in hyperplastic lesions after prosthetic arterial grafting. This study analyzed the effect of ApoJ on human umbilical vein endothelial cell (HUVEC) migration, adhesion, and proliferation. METHODS: Cell migration towards ApoJ + fetal bovine serum (FBS) or vascular endothelial growth factor (VEGF) was evaluated with the use of a microchemotaxis chamber with or without a fibronectin-coated membrane. For migration that involved fibronectin, cells were exposed to ApoJ before or after placement on the membrane. Cell adhesion to fibronectin was studied similarly but without stimulant. The vital dye alamar blue assessed proliferation of ApoJ + FBS- or VEGF-stimulated HUVECs. RESULTS: ApoJ alone did not cause migration or proliferation of HUVECs. Without fibronectin, ApoJ decreased the migration of HUVECs towards FBS or VEGF. When fibronectin was introduced, ApoJ decreased cell migration toward FBS or VEGF and decreased adhesion only when HUVECs in solution were exposed to ApoJ before the placement on fibronectin. ApoJ had no effect on FBS- or VEGF-induced proliferation. CONCLUSIONS: ApoJ inhibits HUVEC migration and adhesion. By altering endothelial function during vascular injury, ApoJ appears to regulate, in part, the early development of intimal hyperplasia after prosthetic arterial grafting.

The impact of diabetes on arterial reconstructions for multilevel arterial occlusive disease.

PURPOSE: Critical limb ischemia due to multilevel arterial occlusive disease often may be treated with an inflow procedure alone; however, a subset patients require a subsequent infrainguinal revascularization for persistence of their symptoms. As diabetic patients typically exhibit a pattern of extensive distal arterial disease, we sought to determine if the presence of diabetes mellitus altered the need for an outflow procedure after inflow bypass. METHODS: A total of 504 patients undergoing inflow bypass for occlusive disease and lower extremity ischemia between 1990 and 1998 were entered prospectively into a computerized vascular registry. Inflow bypass procedures performed were as follows: aortofemoral (370; 73%), axillofemoral (56; 11%), femorofemoral (81; 16%). Of these patients, 79 required subsequent outflow bypass for unresolved ischemic symptoms. Multiple logistic regression analysis was used to analyze the effects of diabetes and multiple other risk factors on the need for an additional outflow procedure. RESULTS: The indications for surgery were limb salvage (78%) and disabling claudication (22%). Overall morbidity was 17.7% (hematoma, 3.8%; wound infection, 2.5%; graft occlusion, 1.3%; myocardial infarction, 2.5%; acute renal failure,1.3%; pulmonary failure, 2.5%; pneumonia, 3.8%). Overall mortality was 0%. Diabetic patients comprised a greater proportion of the total number of patients requiring inflow bypass (301 of 504) as well as a greater proportion of patients requiring inflow and outflow procedures (47 of 79). Diabetes was determined not to be an independent risk factor for the need for multiple revascularization procedures by multiple logistic regression analysis (P >0.10). CONCLUSION: Although patients with diabetes are predisposed to the development of distal arterial occlusive disease, in this study the subgroup of diabetic patients who present with aortoiliac occlusive disease were no more likely than patients without diabetes to require multiple levels of revascularization. These findings provide little rationale for simultaneous inflow and outflow procedures based on the presence of diabetes alone.

Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration.

PURPOSE: Patients with diabetes mellitus (DM) experience progressive macrovascular atherosclerosis and intimal hyperplastic restenosis with increased frequency as compared with nondiabetic patients. These observations suggest that vascular smooth muscle cells (VSMCs) behave in a phenotypically different and more aggressive manner in diabetic patients. In this study, we compared the in vitro rates of proliferation, adhesion, and migration of human VSMCs obtained from diabetic and nondiabetic patients. METHODS: Human VSMC cultures were isolated from 23 diabetic patients (9 artery, 14 vein) and 15 nondiabetic patients (9 artery, 6 vein) with extensive lower extremity atherosclerosis. All patients were between 61 and 78 years of age (average: 68.4 years [diabetic]; 67.3 years [nondiabetic]). All diabetic patients had type 2 DM. Vascular specimens were obtained at the time of amputation from infragenicular arteries and during arterial revascularization from saphenous veins. Cells from passages 2 and 3 were assayed for their proliferative capacity with total DNA fluorescence photometry and for adhesion and migration with a modified Boyden chamber. RESULTS: The average duration of diabetes was 11.6 +/- 4.1 years. The average number of diabetic complications (retinopathy, neuropathy, nephropathy, coronary artery disease) was 2.8 +/- 0.7 per patient. Diabetic VSMCs exhibited abnormal morphology in cell culture with loss of the normal hill and valley configuration. Proliferation was significantly increased in VSMCs of diabetic origin (156 +/- 57 absorption units) as compared with those of nondiabetic origin (116 +/- 42 absorption units) (P <.001). Diabetic VSMCs demonstrated significantly greater adhesion (63.6 +/- 24 per high-power field vs 37.9 +/- 13 per high-power field; P =.002) and migration (397 +/- 151 per low-power field vs 121 +/- 99 per low-power field; P =.001) rates. CONCLUSIONS: Diabetic VSMCs exhibit significantly increased rates of proliferation, adhesion, and migration as well as abnormal cell culture morphology suggestive of abnormal contact inhibition. These observations of human VSMCs in culture are consistent with the increased rate of infragenicular atherosclerosis and the increased rates of restenosis observed clinically in diabetic patients. The atherosclerosis- and intimal hyperplasia-promoting behavior exhibited appears to be intrinsic to the DM-VSMC phenotype and must be considered when designing methods to limit atherosclerosis and intimal hyperplasia in diabetic patients.

Coating of Dacron vascular grafts with an ionic polyurethane: a novel sealant with protein binding properties.

The purpose of this study was to develop a novel sealant that would seal prosthetic vascular graft interstices and be accessible for protein binding. Crimped knitted Dacron vascular grafts were cleaned (CNTRL) and hydrolyzed in boiling sodium hydroxide (HYD). These HYD grafts were sealed using an 11% solids solution of a polyether-based urethane with carboxylic acid groups (PEU-D) via a novel technique that employs both trans-wall and luminal perfusion. Carboxylic acid content, determined via methylene blue dye uptake, was 2.3- and 4.2-fold greater in PEU-D segments (1.0+/-0.27 nmol/mg) as compared to HYD and CNTRL segments, respectively. Water permeation through PEU-D graft (1.1+/-2 ml/cm2 min(-1)) was comparable to collagen-impregnated Dacron (9.8+/-10 ml/cm2 min(-1)). Non-specific 125I-albumin (125I-Alb) binding to PEU-D segments (18+/-3 ng/mg) was significantly lower than HYD and CNTRL segments. 125I-Alb linkage to PEU-D using the crosslinker EDC resulted in 5.7-fold greater binding (103+/-2 ng/mg) than non-specific PEU-D controls. However, covalent linkage of 125I-Alb to PEU-D was 4.9- and 5.9-fold less than CNTRL and HYD segments with EDC, respectively. Thus, ionic polyurethane can be applied to a pre-formed vascular graft, seal the interstices and create "anchor" sites for protein attachment.

Contribution of nerve-axon reflex-related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy.

OBJECTIVE: To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects. RESEARCH DESIGN AND METHODS: The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water. RESULTS: The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers. CONCLUSIONS: Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.

Combined iliac angioplasty and infrainguinal revascularization surgery are effective in diabetic patients with multilevel arterial disease.

The success of percutaneous transluminal angioplasty (PTA) in the treatment of common and external iliac atherosclerotic lesions has been established for the general population. However, several studies have suggested that the presence of diabetes may reduce the effectiveness of iliac angioplasty, particularly in the setting of limb-threatening ischemia requiring concomitant lower extremity revascularization. This study compared the results of iliac artery PTA performed in conjunction with infrainguinal bypass for limb-threatening ischemia for diabetic (DM) and nondiabetic (non-DM) patients. Between 1991 and 2000, 159 PTA were performed in 126 patients (DM = 99/79%, non-DM = 27/21%) in conjunction with subsequent infrainguinal bypass for limb-threatening ischemia (gangrene = 42%, ulcer = 36%, rest pain = 22%). These patients were followed prospectively using a computerized vascular registry. Stents were placed in 34 (21.4%) cases for suboptimal angioplasty results. In this study the combined use of standard surgical and endoluminal modalities for the treatment of multilevel arterial occlusive disease resulted in excellent cumulative patency and limb salvage rates. The presence of diabetes did not alter these favorable results. Multimodal vascular therapy may be used effectively in diabetic patients with limb-threatening ischemia due to multiple levels of arterial occlusion.

Relationship of the 20S proteasome and the proteasome activator PA28 to atherosclerosis and intimal hyperplasia in the human vascular system.

Down-regulation of the proteasome activator PA28 results in abnormal proteasome activation and has been implicated in the development of intimal hyperplasia (IH) in animal models. Demonstration of proteasome and PA28 expression has not yet been documented in the human vascular system. This study sought to define the distribution of the 20S proteasome and its activator PA28 in human vessels and determine the relationship between the expression of the proteasome and PA28 and the development of atherosclerosis and IH. Vascular biopsies were obtained from 70 patients at the time of surgery, were snap frozen and sectioned in 5-micron sections, and prepared using standard histological techniques. The immunoperoxidase technique was used to identify 20S proteasome and PA28 expression in diseased and normal human arteries and veins as well as in patent bypass grafts with and without IH. Expression was graded by a blinded pathologist (scale: 1-4). Repeat quantification of the immunopositive cells was also performed. Expression of 20S proteasome and PA28 was identified in all vascular tissues examined. The proteins were identified predominately within the cytoplasm of vascular smooth muscle cells and endothelial cells. PA28 was more intensely expressed in quiescent regions of the vessel wall as compared to areas undergoing active proliferation and remodeling. PA28-mediated activation of the proteasome may be necessary to maintain normal cellular homeostasis and prevent excessive cellular proliferation in the human vascular system. Abnormalities of proteasome activation may have a significant role in the development of atherosclerosis and IH.

A comparative study of alternative conduits for lower extremity revascularization: all-autogenous conduit versus prosthetic grafts.

PURPOSE: In the absence of an adequate ipsilateral greater saphenous vein, various alternative conduits have been used for the performance of lower extremity revascularization. In this study we compared the effectiveness of all-autogenous arm vein bypass grafts with that of prosthetic grafts. METHODS: Seven hundred forty lower extremity revascularization procedures (506 arm vein, 234 prosthetic) performed between 1990 and 1999 were followed prospectively by means of a computerized vascular registry. RESULTS: Bypass graft configurations were femoro-above-knee-popliteal (26 arm vein, 100 prosthetic); femoro-below-knee-popliteal (38 arm vein, 29 prosthetic); femorotibial (174 arm vein, 55 prosthetic); femoropedal (23 arm vein, 2 prosthetic); popliteotibial/pedal (101 arm vein, 1 prosthetic); and extension "jump" grafts (144 arm vein, 47 prosthetic). The indications for surgery were limb salvage (98.0% arm vein, 89.7% prosthetic) and disabling claudication (2.0% arm vein, 10.3% prosthetic). The mean follow-up was 23.4 months (range, 1 month-7.4 years). Overall patient survival at 4 years was 54% (arm vein) and 69% (prosthetic). Cumulative patency varied with graft configuration. The 1-year primary patency rates for femorotibial grafts were 81.6% +/- 3.6% (arm vein) and 58.0% +/- 8.4% (prosthetic); the 3-year rates were 68.3% +/- 6.1% (arm vein) and 41.1% +/- 9.8% (prosthetic) (P<.01). The 1-year limb salvage rates for femorotibial grafts were 91.1% +/- 2.8% (arm vein) and 69.1% +/- 8. 8% (prosthetic); the 3-year rates were 81.4% +/- 5.6% (arm vein) and 63.2% +/- 10.3% (prosthetic) (P =.02). The 1-year primary patency rates for femoro-below-knee-popliteal grafts were 92.9% +/- 5.1% (arm vein) and 83.4% +/- 8.0% (prosthetic); the 3-year rates were 72.8% +/- 10.1% (arm vein) and 55.5% +/- 12.1% (prosthetic) (P=.05). The 1-year limb salvage rates for femoro-below-knee-popliteal grafts were 100% (arm vein) and 91.3% +/- 7.0% (prosthetic); the 3-year rates were 94.7% +/- 7.3% (arm vein) and 75.3% +/- 14.6% (prosthetic) (P = NS). CONCLUSION: In this study autogenous arm vein grafts demonstrated increased patency and limb salvage, compared with prosthetic grafts. These increases achieved statistical significance in the femoro-below-knee-popliteal and femorotibial configurations. An effort to use an all-autogenous vein conduit is justified on the basis of these results; however, if no autogenous vein is available, prosthetic grafts provide a reasonable alternative to primary amputation.

Gender and carotid endarterectomy: does it matter?

OBJECTIVE: Multiple large series have retrospectively identified female gender as a risk factor for perioperative stroke and death after carotid endarterectomy (CEA). METHODS: Data for all patients who underwent CEA at a single institution from January 1990 to December 1998 were entered into a computerized vascular registry and form the basis of this report. RESULTS: A total of 1298 CEA procedures were performed, of which 520 (40%) were in women and 778 (60%) in men. The mean age was 69.8 +/- 8.7 years for men and 71.2 +/- 8.5 years for women (P <.001). Cardiac risk factors significantly varied among the two groups, with women more likely to have diabetes (42% vs 36%) and hypertension (77% vs 66%), whereas tobacco history was higher among men (85% vs 71%) (P <.05 for all). Female patients were more likely to be asymptomatic at presentation (men, 44% vs women, 51%; P =.022). Postoperative myocardial infarction occurred in eight patients (0.6%) with no differences between men (0.4%) and women (1.0%) (P = not significant). For all adverse postoperative cardiac events (myocardial infarction, congestive heart failure, or arrhythmia), the incidence was 1.9% (25 patients), again with no differences between men (1.5%) and women (2. 5%) (P = not significant). There were 25 postoperative neurologic events (19 strokes, six transient ischemic attacks) among the entire cohort (1.9%), of which 16 were in men (2.1%) and nine in women (1. 6%; P = not significant). The overall postoperative stroke rate was 1.5% (13 [1.7%] of 778 men; 6 [1.2%;] of 520 women; P = not significant). Total operative mortality was 0.3% (3 [0.4%] of 778 men; 1 [0.2%] of 778 women; P = not significant). Late recurrent stenosis requiring operation developed in 14 patients (1.1%) during follow-up (6 [0.8%] of 778 men; 8 [1.5%] of 520 women; P =.19). CONCLUSIONS: Although there is significant variability in cardiac risk factors and presentation, female gender is not a risk factor for stroke, death, or cardiac morbidity after CEA. Women are not at higher risk for reoperation for recurrent stenosis.

Arm vein conduit is superior to composite prosthetic-autogenous grafts in lower extremity revascularization.

PURPOSE: Various alternative conduits have been used for lower extremity revascularization when an adequate ipsilateral greater saphenous vein is absent. This study compared the effectiveness of all-autogenous multisegment arm vein bypass grafts with that of composite grafts composed of combined prosthetic and autogenous conduits. METHODS: One hundred fifty-three lower extremity revascularization procedures performed between 1990 and 1998 were followed up prospectively using a computerized vascular registry. The grafts were composed of spliced arm vein segments with venovenostomy in 122 and of composite prosthetic-autogenous conduit in 31. Arm vein conduit was prepared by means of intraoperative angioscopy for valve lysis and identification of luminal abnormalities in 47.7% of cases. RESULTS: Bypass graft configurations were as follows: femoropopliteal (12 arm vein, 2 composite); femorotibial (75 arm vein, 23 composite); femoropedal (14 arm vein, 6 composite), and popliteo-tibial/pedal (21 arm vein, 0 composite). The indication for surgery was limb salvage in 98% and disabling claudication in 2% of cases. The mean follow-up was 25.1 months (range, 1 month to 7.9 years). Overall survival at 4 years was 51%. Overall patency and limb salvage rates were as follows: primary patency, at 1 year-arm vein, 76.9% +/- 4.8%; composite, 59. 5% +/- 9.6% (P =.02); at 3 years-arm vein, 70.0% +/- 8.0%; composite, 43.7% +/- 12.4% (P <.01); and at 5 years-arm vein, 53.8% +/- 8.7%; composite, 0%; secondary patency, at 1 year-arm vein, 77.5% +/- 4. 6%; composite, 59.8% +/- 9.5% (P =.02); at 3 years-arm vein, 70.7% +/- 7.5%, composite, 44.9% +/- 13.1% (P <.01); at 5 years-arm vein, 57.7% +/- 8.0%; composite, 0%; limb salvage, at 1 year-arm vein, 89. 3% +/- 3.7%; composite, 73.9% +/- 8.9% (P <.01); at 3 years-arm vein, 80.5% +/- 7.0%; composite, 49.6% +/- 14.3% (P <.01); at 5 years-arm vein, 76.3% +/- 9.9%; composite, 0%. CONCLUSION: In this study, multisegment autogenous arm vein was used successfully in a wide variety of lower extremity revascularization procedures and achieved good long-term patency and limb salvage rates, well in excess of those achieved with composite prosthetic-autogenous grafts. The use of autogenous conduit appears to offer superior results to composite conduit in lower extremity revascularization. The superior durability of arm vein makes it one of the alternative conduits of choice when an adequate greater saphenous vein is not available.

Lower extremity revascularization in diabetes: late observations.

HYPOTHESIS: Despite the success of infrainguinal arterial bypass in diabetic limb and foot salvage, optimism remains guarded because of purported high late mortality and limb loss in patients with diabetes. DESIGN: Inception cohort, with minimum 5-year follow-up. SETTING: Tertiary referral center. PATIENTS: Eight hundred forty-three consecutive patients undergoing lower extremity arterial reconstruction from July 1, 1990, through July 31, 1993. INTERVENTION: Infrainguinal arterial bypass with vein graft. MAIN OUTCOME MEASURES: Graft patency, limb salvage, and survival. RESULTS: A total of 962 vein grafts (843 patients) were performed; 795 grafts (82.6%) were performed in patients with diabetes (DM group) and 167 (17.4%) in nondiabetic patients (NDM group). Average age was 68.4 years, and was lower in the DM group (66.2 [range, 27-92 years] vs. 70.5 years [range, 37-96 years]) (P = .005). Inhospital 30-day perioperative mortality was 1.4%, lower in the DM group (0.9% vs. 4.2%) (P = .005). The target vessel was more frequently infrageniculate in the DM group (87% vs. 77%; P = .002). Five-year primary and secondary graft patencies were 74.7% (DM group, 75.6%; NDM group, 71.9%; P = .80) and 76.2% (DM group, 77.0%; NDM group, 73.6%; P = .90), respectively. The 5-year overall limb salvage rate was 87.1%, also unaffected by diabetes (DM group, 87.3%; NDM group, 85.4%; P = .80). Survival at 5 years was 58.1% overall and virtually identical in the DM (58.2%) and NDM groups (58.0%). CONCLUSIONS: Diabetes mellitus does not influence late mortality, graft patency, or limb salvage rates after lower extremity arterial reconstruction. Concern for longterm mortality and limb loss in diabetic patients is unwarranted and should not prevent aggressive attempts at limb salvage.

Effect of porosity on small-diameter vascular graft healing.

Experimental studies have reported that complete healing of small-diameter expanded polytetrafluoroethylene (ePTFE) grafts occurs only if the porosity of the graft is increased, thereby allowing ingrowth of perigraft capillaries yielding endothelial cells. This study investigates the effects of varied graft porosity on the healing characteristics of 2-mm internal diameter (ID) ePTFE grafts interposed in the rabbit common carotid artery. Four groups were evaluated: Group A (n = 8) standard (30-microm pores) ePTFE grafts; Group B (n = 8) increased porosity (60-microm pores) ePTFE grafts; Group C (n = 8) standard ePTFE; and Group D (n = 8) 60-microm ePTFE external graft surface was externally coated with an impermeable layer of polyurethane. Patency was 100% for all groups at 8 weeks. At explantation, the neointima was composed of primarily modified smooth muscle cells. Endothelial cells were only identified at the perianastomotic region using the endothelial cell-specific antibody CD31. The impermeable external polyurethane coating of ePTFE grafts had no effect on neointima formation, regardless of porosity.

The use of arm vein in lower-extremity revascularization: results of 520 procedures performed in eight years.

PURPOSE: The absence of an adequate ipsilateral saphenous vein in patients requiring lower-extremity revascularization poses a difficult clinical dilemma. This study examined the results of the use of autogenous arm vein bypass grafts in these patients. METHODS: Five hundred twenty lower-extremity revascularization procedures performed between 1990 and 1998 were followed prospectively with a computerized vascular registry. The arm vein conduit was prepared by using intraoperative angioscopy for valve lysis and identification of luminal abnormalities in 44.8% of cases. RESULTS: Seventy-two (13. 8%) femoropopliteal, 174 (33.5%) femorotibial, 29 (5.6%) femoropedal, 101 (19.4%) popliteo-tibial/pedal, and 144 (27.7%) extension "jump" graft bypass procedures were performed for limb salvage (98.2%) or disabling claudication (1.8%). The average age of patients was 68.5 years (range, 32 to 91 years); 63.1% of patients were men, and 36.9% of patients were women. Eighty-five percent of patients had diabetes mellitus, and 77% of patients had a recent history of smoking. The grafts were composed of a single arm vein segment in 363 cases (69. 8%) and of spliced composite vein with venovenostomy in 157 cases (30.2%). The mean follow-up period was 24.9 months (range, 1 month to 7.4 years). Overall patency and limb salvage rates for all graft types were: primary patency, 30-day = 97.0% +/- 0.7%, 1-year = 80.2% +/- 2.1%, 3-year = 68.9% +/- 3.6%, 5-year = 54.5% +/- 6.6%; secondary patency, 30-day = 97.0% +/- 0.7%, 1-year = 80.7% +/- 2.1%, 3-year = 70.3% +/- 3.4%, 5-year = 57.5% +/- 6.2%; limb salvage, 30-day = 97.6% +/- 0.7%, 1-year = 89.8% +/- 1.7%, 3-year = 82.1% +/- 3.3%, 5-year = 71.5% +/- 6.9%. Secondary patency and limb salvage rates were greatest at 5 years for femoropopliteal grafts (69.8% +/- 12.8%, 80.7% +/- 11.8%), as compared with femorotibial (59.6% +/- 10. 3%, 72.7% +/- 10.5%), femoropedal (54.9% +/- 25.7%, 56.8% +/- 26.9%, ) and popliteo-tibial/pedal grafts (39.0% +/- 7.3%, 47.6% +/- 15.4%). The patency rate of composite vein grafts was equal to that of single-vein conduits. The overall survival rate was 54% at 4 years. CONCLUSION: Autogenous arm vein has been used successfully in a wide variety of lower-extremity revascularization procedures and has achieved excellent long- and short-term patency and limb salvage rates, higher than those generally reported for prosthetic or cryopreserved grafts. Its durability and easy accessibility make it an alternative conduit of choice when an adequate saphenous vein is not available.

The use of gastric tonometry in the assessment of celiac artery compression syndrome.

This report describes the use of gastric tonometry to measure gastric mucosal ischemia/intestinal mucosa pH (pHi) in a patient treated for celiac artery compression syndrome. Significant gastric mucosal ischemia was demonstrated prior to celiac artery decompression as indicated by a pHi of 7.29. The ischemia was relieved by celiac artery decompression, with an increase in the pHi to 7.48. The patient experienced complete relief of his symptoms after surgical decompression and remains asymptomatic 14 months after surgery. Gastric tonometry provides an objective measurement of intestinal perfusion and ischemia in the treatment of celiac artery compression syndrome.

The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes.

Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy (HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean +/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/- 67%; increase over baseline) compared to premenopausal diabetic women (87 +/- 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and postmenopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation.

Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria.

OBJECTIVE: Using von Willebrand Factor (vWF) as a marker of endothelial function, previous studies have shown that the development of microalbuminuria is associated with the onset of endothelial dysfunction in individuals with type 2 diabetes. We tested the hypothesis that endothelial dysfunction is already evident in normoalbuminuric individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We used laser Doppler imaging scanning to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). Multiple indicators of endothelial function--soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM), vWF, and microvascular reactivity--were measured in 20 healthy control subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio < 30 micrograms/mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary albumin/creatinine ratio between 30 and 300 micrograms/mg) individuals with type 2 diabetes. RESULTS: Serum sICAM and sVCAM levels were elevated in the normoalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy control subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01). Furthermore, the microvascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusion over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals with diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47) (P < 0.05). In contrast, plasma vWF was elevated only in the microalbuminuric individuals with diabetes (129 +/- 35%) compared with the normoalbuminuric individuals with diabetes (110 +/- 34) and healthy control subjects (111.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood glucose was the most important contributing factor to the variation in microvascular reactivity and sVCAM, whereas insulin resistance (by homeostasis model assessment) was the most important contributing factor to the variation in sICAM. Addition of all clinical and biochemical measures explained only 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. CONCLUSIONS: Multiple markers of endothelial dysfunction were evident in normoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before the development of microalbuminuria.