Simulated Thrombin Generation in the Presence of Surface-Bound Heparin and Circulating Tissue Factor

An expanded computational model of surface induced thrombin generation was developed that includes hemodynamic effects, 22 biochemical reactions and 44 distinct chemical species. Surface binding of factors V, VIII, IX, and X was included in order to more accurately simulate the formation of the surface complexes tenase and prothrombinase. In order to model these reactions, the non-activated, activated and inactivated forms were all considered. This model was used to investigate the impact of surface bound heparin on thrombin generation with and without the additive effects of thrombomodulin (TM). In total, 104 heparin/TM pairings were evaluated (52 under venous conditions, 52 under arterial conditions), the results demonstrating the synergistic ability of heparin and TM to reduce thrombin generation. Additionally, the role of circulating tissue factor (TF[subscript p]) was investigated and compared to that of surface-bound tissue factor (TF[subscript s]). The numerical results suggest that circulating TF has the power to amplify thrombin generation once the coagulation cascade is already initiated by surface-bound TF. TF[subscript p] concentrations as low as 0.01 nM were found to have a significant impact on total thrombin generation.National Institutes of Health (U.S.) (Grants HL106018 and HL56819

Continued expansion of aortic necks after endovascular repair of abdominal aortic aneurysms

AbstractBackground: Longitudinal studies have revealed that the aortic segment proximal to an infrarenal abdominal aortic aneurysm (AAA) is at risk for continued enlargement after a standard aneurysm repair. Similarly, preliminary reports have shown expansion of one or both aortic necks after endovascular repair. Although some investigators have suggested that this may be a transient effect, continued dilatation at the endograft attachment site could effect the overall device stability. Methods: As part of a multi-institutional trial of endovascular grafting for the treatment of AAA, 59 patients were successfully implanted with straight endografts between February 1993 and January 1995. A morphometric analysis of aortic neck size was undertaken with serial review of computed tomography scans available through April 1997. The neck sizes at both graft attachment sites were measured, with investigators blinded to patient identity and date of scan. Changes in minor diameter were defined, annual interval expansion rates were calculated, and the data were correlated with endoleak, device migration, aneurysm size change, endograft diameter, attachment system fractures, and initial preimplant neck size. Results: Significant aortic neck enlargement, particularly at the level of the distal neck, was observed for at least 24 months after AAA repair. The annual interval dilation rates of the proximal aortic neck were 0.7 ± 2.1 mm/y (P = .023) and 0.9 ± 1.9 (P = .008) mm/yr during the first and second years, respectively. Enlargement of the distal neck during the observation period was more marked, with corresponding annual expansion rates of 1.7 ± 2.9 mm/y (P < .001) and 1.9 ± 2.5 (P < .001) mm/year. In 5 patients (14%), the minor diameter of the distal neck was at least 6 mm larger than the preimplant diameter of the graft. Migration of the distal attachment system was observed in 3 of these 5 patients. Expansion rates did not have a statistically significant correlation with initial neck size, endograft dimensions, aneurysm size change, presence of endoleak, or attachment system fracture. Conclusions: Aortic neck enlargement was observed for at least 2 years after endovascular grafting. Close patient follow-up remains mandatory in lieu of the potential risk of late failure as a result of continued aortic expansion. The relative contribution of device design to this phenomenon will need to be defined. (J Vasc Surg 1998;28:422-31.

Cell behavior on a CCN1 functionalized elastin-mimetic protein polymer

a b s t r a c t We report the design of an elastin-mimetic triblock copolymer with the ability to guide endothelial cell adhesion, spreading, and migration while maintaining the elastomeric properties of the protein polymer. The V2 ligand sequence from matricellular protein CCN1 (cysteine-rich 61, CYR61) was multimerized and cloned into elastin polymer LysB10, creating LysB10.V2. Cell adhesion studies demonstrated that a LysB10.V2 surface density of at least 40 pmol/cm 2 was required to elicit cell attachment. Peptide blocking studies confirmed V2 specific engagement with integrin receptor a v b 3 (P &lt; 0.05) and we observed the formation of actin stress fiber networks and vinculin clustering, characteristic of focal adhesion assembly. Haptotatic migration assays demonstrated the ability of LysB10.V2 surfaces to stimulate migration of endothelial cells (P &lt; 0.05). Significantly, we illustrated the ability of LysB10.V2 to support a quiescent endothelium. The CCN1 molecule functions to support many key biological processes necessary for tissue repair and thus presents a promising target for bioengineering applications. Collectively, our results demonstrate the potential to harness CCN1 specific function in the design of new scaffold materials for applications in regenerative medicine

Left subclavian artery coverage during thoracic endovascular aortic repair and risk of perioperative stroke or death

IntroductionLeft subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR) is often necessary due to anatomic factors and is performed in to up to 40% of procedures. Despite the frequency of LSA coverage during TEVAR, reported associations with risk of periprocedural stroke or death are inconsistent in reported literature. We examined the 2005-2008 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data file to determine associations between LSA coverage during TEVAR and risk of perioperative stroke or death.MethodsCurrent procedural terminology (CPT) codes were used to identify patients undergoing TEVAR, LSA coverage, and subclavian revascularization. Patients undergoing coronary bypass, ascending aortic repair, abdominal aortic aneurysm repair, or nonvascular intra-abdominal procedures during the same operation were excluded. Perioperative stroke and mortality associations with LSA coverage were examined using logistic regression models for each outcome. Significance was assessed at α = 0.05, with univariable P < .05 required for multivariable model entry.ResultsEight hundred forty-five TEVAR procedures were identified, of which 52 patients were excluded due to additional major procedures performed with TEVAR. Seven hundred thirty-three of the remaining 793 procedures included CPT codes indicating primary placement of an initial thoracic endograft and form the basis of this analysis. LSA coverage occurred in 279 procedures (38%). Thirty-day stroke and mortality rates were 5.7% and 7.0%, respectively. LSA coverage was associated with increased 30-day risk of stroke in multivariable modeling (odds ratio [OR], 2.17 95% confidence interval [CI], 1.13-4.14; P = .019). Other significant multivariable risk factors for stroke included proximal aortic cuff placement during TEVAR (OR, 2.58; 95% CI, 1.30-5.16; P = .007) and emergency procedure status (OR, 3.60; 95% CI, 1.87-6.94; P < .001). No significant association between LSA coverage and perioperative mortality was identified (univariable OR, 1.70; 95% CI, 0.98-2.93; P = .0578).ConclusionLSA coverage during thoracic endovascular repair is associated with increased risk of perioperative stroke following TEVAR. Further evidence is needed to determine whether procedural modifications, including LSA revascularization, reduce the incidence of stroke associated with TEVAR

Prosthetic graft infections involving the femoral artery

BackgroundProsthetic graft infection is a major complication of peripheral vascular surgery. We investigated the experience of a single institution over 10 years with bypass grafts involving the femoral artery to determine the incidence and risk factors for prosthetic graft infection.MethodsA retrospective cohort single-institution review of prosthetic bypass grafts involving the femoral artery from 2001 to 2010 evaluated patient demographics, body mass index, comorbidities, indications, location of bypass, type of prosthetic material, case urgency, and previous ipsilateral bypass or percutaneous interventions and evaluated the incidence of graft infections, amputations, and mortality.ResultsThere were 496 prosthetic grafts identified with a graft infection rate of 3.8% (n = 19) at a mean follow-up of 27 months. Multivariable analysis showed that redo bypass (hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.2-15.0), active infection at the time of bypass (HR, 5.2; 95% CI, 1.9-14.2), female gender (HR, 4.5; 95% CI, 1.6-12.7), and diabetes mellitus (HR, 4.6; 95% CI, 1.5-14.3) were significant predictors of graft infection. Graft infection was predictive of major lower extremity amputation (HR, 9.8; 95% CI, 3.5-27.1), as was preoperative tissue loss (HR, 4.7; 95% CI, 1.8-11.9). Graft infection did not predict long-term mortality; however, chronic renal insufficiency (HR, 2.3; 95% CI, 1.6-3.4), tissue loss (HR, 1.4; 95% CI, 1.0-1.9), and active infection (HR, 2.3; 95% CI, 1.6-3.4) did. Infected grafts were removed 79% of the time. Staphylococcus epidermidis (37%) and methicillin-sensitive Staphylococcus aureus (26%) were the most common pathogens isolated.ConclusionsRedo bypass, female gender, diabetes, and active infection at the time of bypass are associated with a higher risk for prosthetic graft infection and major extremity amputation but do not confer an increased risk of mortality. Autologous vein for lower extremity bypass and endovascular interventions should be considered when feasible in high-risk patient