Arterial shear stress reduces eph-b4 expression in adult human veins.

Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

The Nogo-B-PirB axis controls macrophage-mediated vascular remodeling.

OBJECTIVE: Nogo-B mediates vascular protection and facilitates monocyte- and macrophage-dependent vascular remodeling. PirB is an alternate receptor for Nogo-B, but a role for the Nogo-PirB axis within the vascular system has not been previously reported. We examined whether Nogo-B or PirB play a role in regulating macrophage-mediated vascular remodeling and hypothesized that endothelial Nogo-B regulates vein graft macrophage infiltration via its alternate receptor PirB. METHODS: Vein grafts were performed using Nogo and PirB wild type and knockout mice. Human vein grafts were similarly analyzed. The hindlimb ischemia model was performed in PirB wild type and knockout mice. Accompanying in vitro work included isolation of macrophages from PirB wild type and knockout mice. RESULTS: Increased Nogo-B and PirB mRNA transcripts and protein expression were observed within mouse and human vein grafts. Both Nogo knockout and PirB knockout vein grafts showed increased wall thickness and increased numbers of F4/80-positive macrophages. Macrophages derived from PirB knockout mice had increased adhesion to fibronectin, increased EC-specific binding, and increased numbers of mRNA transcripts of M2 markers as well as MMP3 and MMP9. PirB knockout vein grafts had increased active MMP9 compared to wild type vein grafts. PirB knockout mice had increased recovery from hindlimb ischemia and increased macrophage infiltration compared to wild type mice. CONCLUSIONS: Vein graft adaptation shows increased expression of both Nogo-B and PirB. Loss of PirB, or its endothelial ligand Nogo-B, results in increased inflammatory cell infiltration and vein graft wall thickening. These findings suggest that PirB regulates macrophage activity in vein grafts and that Nogo-B in the vein graft limits macrophage infiltration and vein graft thickening. PirB may play a more general role in regulating macrophage responses to vascular injury. Macrophage inhibition via Nogo-PirB interactions may be an important mechanism regulating vein graft adaptation to the arterial circulation.

Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells.

BACKGROUND: During vein graft adaptation to the arterial circulation, vascular endothelial growth factor (VEGF) A expression transiently increases before becoming downregulated; however, the role of VEGF-A in venous remodeling is not clear. In addition, although VEGF-A stimulates angiogenesis and determines arterial identity in nascent arterial endothelial cells (EC), the role of VEGF-A in regulating identity in adult venous EC is also not clear. MATERIALS AND METHODS: EC, wild type (EphB4+/+) or heterozygous knockout (EphB4+/-), were stimulated with VEGF-A (0-100 ng/mL) and examined with quantitative polymerase chain reaction and western blotting. RESULTS: VEGF-A (100 ng/mL) inhibited expression of EphB4 and stimulated expression of delta-like ligand 4 (dll4) but did not stimulate either notch or EphrinB2 expression in adult venous EC. Pretreatment with VEGF receptor 2-neutralizing antibody abolished VEGF-stimulated downregulation of EphB4 but not the upregulation of dll4. Pretreatment with PD98059 or wortmannin showed that VEGF-A downregulation of EphB4 and upregulation of dll4 are mitogen-activated protein kinase kinase and extracellular signal-regulated kinase dependent but phosphatidylinositol 3 kinase-Akt independent. Compared with VEGF-induced EphB4 downregulation and dll4 upregulation in control EC, reduced EphB4 signaling in EphB4+/- EC showed even further downregulation of EphB4 and upregulation of dll4. CONCLUSIONS: Despite the genetic programming of arterial and venous EC fate, VEGF-A can repress venous identity in adult venous EC without induction of arterial identity. These changes in adult EC in vitro recapitulate the changes in identity described during vein graft adaptation to the arterial environment in vivo.

Reduced adult endothelial cell EphB4 function promotes venous remodeling.

Reduced EphB4 expression is observed during vein graft adaptation and is associated with increased venous wall thickening. These findings suggest that EphB4 may mediate normal adult venous endothelial cell (EC) function and vein graft adaptation. We therefore tested the functional significance of EphB4 using EC with genetically reduced EphB4 signaling. EC were isolated from EphB4(+/+) and EphB4(+/-) mice. In vitro function was assessed through EC proliferation, migration, nitric oxide (NO) synthesis, and chemokine production. A mouse vein graft model was used to correlate in vitro findings with in vivo vein grafts. Smooth muscle cells (SMC) were subjected to proliferation and migration assays using EphB4(+/+) and EphB4(+/-) EC-conditioned medium. EphB4(+/-) EC exhibited diminished proliferation (P < 0.0001, n = 6), migration (P < 0.0001, n = 3), and NO production (P = 0.0012, n = 3). EphB4(+/-) EC had increased VEGF-A mRNA (P = 0.0006, n = 6) and protein (P = 0.0106, n = 3) as well as increased secretion of VEGF-A (P = 0.0010, n = 5), PDGF-BB (P < 0.0001, n = 6), and TGF-ß1 (P < 0.0001, n = 6). EphB4(+/-)-conditioned medium promoted SMC proliferation (P < 0.0001, n = 7) and migration (P = 0.0358, n = 3). Vein grafts and EphB4(+/-) EC showed similarity with regard to VEGF-A and eNOS mRNA and protein expression. In conclusion, reduced venous EC EphB4 function is associated with a proangiogenic and mitogenic phenotype. EphB4(+/-) EC have increased secretion of SMC mitogens and reduced NO production that correlate with the thickened neointima formed during vein graft adaptation. These findings suggest that EphB4 remains active in adult venous EC and that loss of EphB4 plays a role in vein graft adaptation.

Total arch replacement in a patient with an unusual vascular anatomy.

A 69-year-old man with a history of infectious abdominal aortic aneurysm, which had resulted in removal of the infrarenal abdominal aorta and bilateral axillofemoral bypass 9 years previously, underwent total arch replacement for an aortic arch aneurysm. The patient had the interrupted abdominal aorta and highly atherosclerotic proximal aorta, which precluded the possibility of endovascular stent grafting in combination with arch vessel debranching technique. Therefore, open arch repair was the only treatment option. The operation was successful with his axillofemoral bypass graft being exposed and used for arterial inflow during cardiopulmonary bypass, including integrated selective antegrade cerebral perfusion.

Therapeutic strategies to combat neointimal hyperplasia in vascular grafts.

Neointimal hyperplasia (NIH) in bypass conduits such as veins and prosthetic grafts is an important clinical entity that limits the long-term success of vascular interventions. Although the development of NIH in the conduits shares many of the same features of NIH that develops in native arteries after injury, vascular grafts are exposed to unique circumstances that predispose them to NIH, including surgical trauma related to vein handling, hemodynamic changes creating areas of low flow, and differences in biocompatibility between the conduit and the host environment. Multiple different approaches, including novel surgical techniques and targeted gene therapies, have been developed to target and prevent the causes of NIH. Recently, the PREVENT trials, the first molecular biology trials in vascular surgery aimed at preventing NIH, have failed to produce improved clinical outcomes, highlighting the incomplete knowledge of the pathways leading to NIH in vascular grafts. In this review, we aim to summarize the pathophysiologic pathways that underlie the formation of NIH in both vein and synthetic grafts and discuss current and potential mechanical and molecular approaches under investigation that may limit NIH in vascular grafts.

Age-related neointimal hyperplasia is associated with monocyte infiltration after balloon angioplasty.

Carotid angioplasty is associated with adverse events in elderly patients; it is unclear whether this is related to an altered inflammatory axis. The carotid arteries of young (6 months) or aged (22-24 months) Fischer 344 rats were balloon injured. Aged rats had reduced lumen area (0.18 ± 0.03 vs 0.24 ± 0.01 mm(2), p = .02) and increased neointimal thickening (0.15 ± 0.04 vs 0.08 ± 0.03 mm(2), p = .006). Aged rats had increased circulating monocytes (96 ± 21 vs. 54 ± 7; p = .002) as well as increased numbers of monocytes at the post-angioplasty site. Aged rats had sustained monocyte chemotactic protein-1 expression after angioplasty but young rats did not. Aged arteries also exhibited defective vasorelaxation and abnormal eNOS localization. Aged (≥80 years) human patients with high-grade carotid stenosis had increased number of monocytes (9.1% ± 0.4%) compared with younger (65-80 years) patients (8.1% ± 0.3%, p = .013). Aged rats develop neointimal hyperplasia after carotid angioplasty with increased numbers of monocytes, and elderly humans with carotid stenosis have increased numbers of circulating monocytes. These preliminary results may suggest a role for monocytes in the response to carotid angioplasty.

Inhibition of Mitogen Activated Protein Kinase Activated Protein Kinase II with MMI-0100 reduces intimal hyperplasia ex vivo and in vivo.

Vein graft intimal hyperplasia remains the leading cause of graft failure, despite many pharmacological approaches that have failed to translate to human therapy. We investigated whether local suppression of inflammation and fibrosis with MMI-0100, a novel peptide inhibitor of Mitogen Activated Protein Kinase Activated Protein Kinase II (MK2), would be an alternative strategy to reduce cell proliferation and intimal hyperplasia. The cell permeant peptide MMI-0100 was synthesized using standard Fmoc chemistry. Pharmacological doses of MMI-0100 induced minimal human endothelial and smooth muscle cell proliferation (30% and 12% respectively). MMI-0100 suppressed IL-6 expression to control levels, without effect on IL-8 expression. MMI-0100 caused sodium nitroprusside induced smooth muscle cell relaxation and inhibited intimal thickening in human saphenous vein rings in a dose-dependent fashion. In a murine aortic bypass model, MMI-0100 reduced intimal thickness in vein grafts by 72%, and there were fewer F4/80-reactive cells in vein grafts treated with MMI-0100. MMI-0100 prevents vein graft intimal thickening ex vivo and in vivo. These results suggest that inhibition of MK2 with the cell-permeant peptide MMI-0100 may be a novel strategy to suppress fibrotic processes such as vein graft disease.

Allogeneic human tissue-engineered blood vessel.

BACKGROUND: Arterial bypass graft implantation remains the primary therapy for patients with advanced cardiovascular disease; however, there is no available synthetic small-diameter vascular graft. METHODS: Tissue-engineered vessels were grown from human smooth muscle cells that were seeded on a biodegradable scaffold using a biomimetic perfusion system. The human tissue-engineered vessels (hTEV) were decellularized by a two-step process using a combination of detergents and hypertonic solutions. The mechanical characteristics were assessed by suture retention strength and burst pressure. The decellularized hTEV were implanted as aortic interpositional grafts in nude rats to evaluate in vivo performance as an arterial graft over a 6-week period. RESULTS: The human tissue-engineered structure formed a vessel composed of smooth muscle cells and the extracellular matrix proteins, including collagen. After decellularization, the collagen matrix remained intact while the cellular components were removed. The mechanical strength of the hTEV after decellularization was similar to human vein in vitro, with a burst pressure of 1,567 ± 384 mm Hg (n = 3) versus 1,680 ± 307 mm Hg for human saphenous vein. The hTEVs had a high patency rate (four of five grafts) without evidence of rupture or aneurysm over a 6-week period as an aortic interpositional graft in a nude rat model. Histologic analysis showed a thin neointima with a confluent endothelium and a subendothelial layer of smooth muscle cells on the explanted tissue-engineered vessels. Transmission electron microscopy on the explanted tissue demonstrated elastin formation in the neointima and intact residual collagen fibers from the tissue-engineered vessel. CONCLUSIONS: The hTEV had a high patency rate and remained mechanically stable as an aortic interpositional graft in a nude rat. The vessel supported the growth of a neointima with endothelial cells and smooth muscle cells. The host remodeling suggested the engineered matrix had a positive effect to create a regenerated vascular graft.

Age-related Notch-4 quiescence is associated with altered wall remodeling during vein graft adaptation.

BACKGROUND: The link of aging to specific mechanisms of vascular biology is not well understood. We have previously shown that aging is associated with increased vein graft wall thickness and that this process involves the VEGF-Delta/Notch-ephrin/Eph cascade. Therefore, we examined whether Dll-4 or Notch-4 are differentially expressed, according to age, during vein graft adaptation. MATERIALS AND METHODS: Vein grafts were performed in 6-mo and 24-mo Fischer 344 rats. Gene expression was analyzed by quantitative real-time PCR, and the distribution of Dll-4 and Notch-4 was observed by immunofluorescence. RESULTS: The expression of Dll-4 and Notch-4 was reduced in vein grafts performed in aged rats compared with the expression in young adult rats. Both Dll-4 and Notch-4 were distributed in vein graft endothelium as well as the outer adventitia, with reduced amounts in the outer adventitia of aged vein grafts. Aged veins had reduced eNOS membrane targeting and colocalization with caveolin-1 as well as reduced eNOS protein expression in comparison to young adult veins. In an exchange model between young and aged animals, heterogeneous vein grafts (Yo(Ag) and Ag(Yo)) showed significantly thicker neointima compared with young (Yo(Yo)) controls, and had Notch-4-positive cells, but not Dll-4-positive cells, diminished in the adventitia. Vein grafts that were air-denuded of endothelium did not show any adaptation to the arterial environment and also lacked both Dll-4 and Notch-4 expression at 3 wk. CONCLUSIONS: During vein graft adaptation to the arterial environment, both Dll-4 and Notch-4 expression are down-regulated in an aged, but not a young, background. Loss of Notch-4 is associated with loss of attenuation of neointima. The delta-Notch signaling pathway may be active during vein graft adaptation.

Basic data related to surgical infrainguinal revascularization procedures: a twenty year update.

In 1990, Dalman and Taylor published a compilation of reported data that were identified by them as related to infrainguinal revascularization procedures in peripheral vascular surgery during the decade of the 1980s. The intervening 20 years has seen revolutionary advances in the field of peripheral vascular surgery, especially in the adoption of endovascular techniques, and an explosion of data related to emerging technologies in the field of infrainguinal revascularization. The tables in this manuscript reflect the evolution of our surgical knowledge during the turn of the 21st century. The superior patency of autologous saphenous vein in all positions is reaffirmed.

Eph-B4 prevents venous adaptive remodeling in the adult arterial environment.

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4-Cav-1-mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults.

Elevated monocytes in patients with critical limb ischemia diminish after bypass surgery.

BACKGROUND: Mononuclear cells (MNC) increase neovascularization and ulcer healing after injection into an ischemic extremity. Circulating MNC are composed of lymphocytes (85%), monocytes (15%), and endothelial progenitor cells (EPC; 0.03%). We hypothesized that ischemic limbs secrete paracrine signals to recruit bone marrow-derived monocytes and EPC into the circulation, such that patients with critical limb ischemia (CLI) have increased circulating monocytes compared with control patients. We also hypothesized that circulating monocytes and EPC recruitment decrease after resolution of ischemia with successful revascularization. METHODS: We reviewed the records of all patients at the VA Connecticut Healthcare System undergoing primary, functionally successful, lower extremity peripheral bypass surgery between 2002 and 2007, but only including patients with both preoperative and postoperative (>4 mo) complete blood counts with differentials. RESULTS: Patients with CLI (n = 24) had elevated preoperative monocyte counts compared with control patients (n = 8) (0.753 ± 0.04 versus 0.516 ± 0.05; P = 0.0046), whereas the preoperative lymphocyte counts were not significantly different. After revascularization, ischemic patients had decreased monocyte counts compared with control patients (-20% versus + 55%; P = 0.0003), although lymphocyte counts were unchanged in both groups. Diabetic patients also had reduced postoperative monocyte counts (-32% versus + 13%; P = 0.035). Multivariable logistic regression demonstrated that the only factor that independently predicted reduced postoperative monocyte count was preoperative CLI (P = 0.038). CONCLUSIONS: Patients with CLI have increased numbers of circulating monocytes, and the monocyte number decreases with resolution of ischemia after successful revascularization. Circulating monocytes may be a clinically useful perioperative marker in patients with CLI undergoing vascular surgery.

Mechanisms of vein graft adaptation to the arterial circulation: insights into the neointimal algorithm and management strategies.

For patients with coronary artery disease or limb ischemia, placement of a vein graft as a conduit for a bypass is an important and generally durable strategy among the options for arterial reconstructive surgery. Vein grafts adapt to the arterial environment, and the limited formation of intimal hyperplasia in the vein graft wall is thought to be an important component of successful vein graft adaptation. However, it is also known that abnormal, or uncontrolled, adaptation may lead to abnormal vessel wall remodeling with excessive neointimal hyperplasia, and ultimately vein graft failure and clinical complications. Therefore, understanding the venous-specific pathophysiological and molecular mechanisms of vein graft adaptation are important for clinical vein graft management. Of particular importance, it is currently unknown whether there exist several specific distinct molecular differences in the venous mechanisms of adaptation that are distinct from arterial post-injury responses; in particular, the participation of the venous determinant Eph-B4 and the vascular protective molecule Nogo-B may be involved in mechanisms of vessel remodeling specific to the vein. This review describes (1) venous biology from embryonic development to the mature quiescent state, (2) sequential pathologies of vein graft neointima formation, and (3) novel candidates for strategies of vein graft management. Scientific inquiry into venous-specific adaptation mechanisms will ultimately provide improvements in vein graft clinical outcomes.

Primary stent placement for iliac artery chronic total occlusions.

PURPOSE: The purpose of this study was to evaluate the technical and mid-term results of primary stent placement for chronic total occlusions (CTO) of the iliac artery, in comparison to stent placement for iliac artery stenosis. METHODS: A retrospective study was carried out on 114 consecutive limbs with 24 CTOs and 90 stenoses of the iliac artery that underwent primary stent placement. Primary, assisted primary patency, and limb salvage rates were determined in accordance with the Society for Vascular Surgery guidelines. RESULTS: Angiographic and intravascular ultrasonographic success was achieved in all 114 limbs (100%). Three major complications, including 1 distal embolism and 2 arterial ruptures, occurred in the CTO group. The 2-year primary patency rate in the CTO group was as high as that observed in the stenosis group (91% vs 89%). There were also no significant differences in the assisted primary patency, limb salvage, and survival rates between the two groups. CONCLUSIONS: Our results indicate that primary stent placement is a safe and effective treatment for iliac CTOs. However, major complications, including distal embolization and iliac artery rupture, remain a significant problem, and caution should therefore be exercised when performing this technique for iliac CTOs.

Endovascular revascularization of diseased native arteries following failed aortoiliac and femoropoliteal grafts: report of two cases.

Arterial reconstructions for lower-extremity ischemia, comprising aortoiliac, aortofemoral, and femoropopoliteal bypasses, and other procedures, have an intrinsic tendency to fail as time elapses. Surgical approaches to arteries in patients who have failed bypass grafts are often rendered more difficult, or even impossible to use, by surgical scarring or infection. The authors report two cases in which the diseased native arteries treated with failed aortoiliac and femoropopliteal bypass grafts were successfully recanalized with primary stent placement. Our cases show that stent placement of the diseased native arteries can represent a possible option for the treatment of failed bypass grafts.

Surgically implantable magnetic resonance angiography coils improve resolution to allow visualization of blood flow dynamics.

BACKGROUND: Magnetic resonance angiography (MRA) is clinically useful but of limited applicability to small animal models due to poor signal resolution, with typical voxel sizes of 1 mm(3) that are insufficient to analyze vessels of diameter <1 mm. We determined whether surgically implantable, extravascular MRA coils increase signal resolution adequately to examine blood flow dynamics METHODS: A custom MRA coil was surgically implanted near the carotid artery of a New Zealand White rabbit. A stenosis was created in the carotid artery to induce complicated, non-laminar flow. Phase contrast images were obtained on multiple axial planes with 3T MRA and through-plane velocity profiles were calculated under laminar and complicated flow conditions. These velocity profiles were fit to a laminar flow model using ordinary least squares in order to quantify the degree of flow complication (Matlab). Flow was also measured with a Doppler flow probe; vessel diameters and flow velocities were compared with duplex ultrasound RESULTS: Carotid artery blood flow was 24.7 +/- 2.6 ml/min prior to stenosis creation and reduced to 12.0 +/- 1.7 ml/min following injury (n=3). An MRA voxel size of 0.1 x 0.1 x 5 mm was achieved. The control carotid artery diameter was 1.9 +/- 0.1 mm, and cross-sectional images containing 318 +/- 22 voxels were acquired (n=26). Velocity profiles resembled laminar flow proximal to the stenosis, and then became more complicated just proximal and distal to the stenosis. Laminar flow conditions returned downstream of the stenosis CONCLUSION: Implantable, extra-vascular coils enable small MRA voxel sizes to reproducibly calculate complex velocity profiles under both laminar and complicated flow in a small animal model. This technique may be applied to study blood flow dynamics of vessel remodeling and atherogenesis.

Utility of telomerase-pot1 fusion protein in vascular tissue engineering.

While advances in regenerative medicine and vascular tissue engineering have been substantial in recent years, important stumbling blocks remain. In particular, the limited life span of differentiated cells that are harvested from elderly human donors is an important limitation in many areas of regenerative medicine. Recently, a mutant of the human telomerase reverse transcriptase enzyme (TERT) was described, which is highly processive and elongates telomeres more rapidly than conventional telomerase. This mutant, called pot1-TERT, is a chimeric fusion between the DNA binding protein pot1 and TERT. Because pot1-TERT is highly processive, it is possible that transient delivery of this transgene to cells that are utilized in regenerative medicine applications may elongate telomeres and extend cellular life span while avoiding risks that are associated with retroviral or lentiviral vectors. In the present study, adenoviral delivery of pot1-TERT resulted in transient reconstitution of telomerase activity in human smooth muscle cells, as demonstrated by telomeric repeat amplification protocol (TRAP). In addition, human engineered vessels that were cultured using pot1-TERT-expressing cells had greater collagen content and somewhat better performance in vivo than control grafts. Hence, transient delivery of pot1-TERT to elderly human cells may be useful for increasing cellular life span and improving the functional characteristics of resultant tissue-engineered constructs.

Vasodilator response correlates with outcome in chronic critical limb ischemia.

BACKGROUND: There are few predictors of limb salvage in patients with critical limb ischemia (CLI). We evaluated the accuracy of correlation of skin perfusion pressure (SPP) measurements in response to vasodilation to clinical outcome. METHODS: Patients with CLI were evaluated by SPP at baseline. After injection of the vasodilator alprostadil, SPP was re-evaluated at 120 min and at day 7. RESULTS: Patients showing clinical improvement demonstrated increased SPP in response to vasodilation (120 min: 34.12+/-2.44 to 48.33+/-3.41 mm Hg, P < 0.01; day 7: 33.13+/-3.14 to 45.83+/-3.79 mm Hg, P < 0.01), whereas patients who clinically deteriorated demonstrated no increase in SPP (120 min: 30.00+/-2.67 to 35.00+/-2.31 mm Hg, P = 0.086; day 7: 35.00+/-3.54 to 27.5+/-4.33 mm Hg, P = 0.22). CONCLUSIONS: Prognosis for limb salvage correlated with SPP improvement post-vasodilator treatment after both early and late time points. Measurement of SPP after vasodilator treatment may be clinically useful in the treatment of patients with CLI. A multi-center trial of SPP in response to vasodilators is warranted.

Patches for carotid artery endarterectomy: current materials and prospects.

Patch angioplasty is commonly performed after carotid endarterectomy. Randomized prospective trials and meta-analyses have documented improved rates of perioperative and long-term stroke prevention as well as reduced rates of restenosis for patches compared with primary closure of the arteriotomy. Although use of vein patches is considered to be the gold standard for patch closure, newer generations of synthetic and biologic materials rival outcomes associated with vein patches. Future bioengineered patches are likely to optimize patch performance, both by achieving minimal stroke risk and long-term rates of restenosis as well as by minimizing the risk of unusual complications of prosthetic patches such as infection and pseudoaneurysm formation. In addition, lessons from bioengineered patches will likely enable construction of bioengineered and tissue-engineered bypass grafts.