81.06 Does Kidney Transplant Increase the Risk of Ipsilateral Lower Extremity Deep Venous Thrombosis?

Posted on January 31, 2019

S. Ahmed1, D. Kim2, Z. Al Adas1, M. Weaver1, J. Lin2, T. Nypaver1, A. Shepard1, L. Malinzak2, L. S. Kabbani1  1Henry Ford Health System,Department Of Vascular Surgery,Detroit, MI, USA 2Henry Ford Health System,Department Of Transplant Surgery,Detroit, MI, USA

Introduction:

There is limited information on the development and laterality of symptomatic deep vein thrombosis (DVT) following kidney transplantation. In this study, we want define the incidence of DVT in this population and determine if the side of the DVT corresponds to the side of the transplanted kidney.

Methods:

We performed a retrospective review of all kidney transplant recipients from January, 2004 to August, 2014 at our institution and who subsequently developed symptomatic DVT. Kidney transplant recipients and confirmed DVT patients were obtained as two separate data files and were matched to obtain our cohort. Patients with concomitant pancreatic transplants, repeat, and bilateral kidney transplants were excluded. We used Cohen’s kappa statistic to test the agreement between the surgical incision site of the kidney transplant to the side at which the DVT occurred.

Results:

A total of 1827 kidney transplant recipients were performed between January 2004 to August 2014. A total of 877 kidney transplant recipients met the inclusion criteria as our total cohort. From our total cohort, 217 recipients underwent ultrasounds to rule out DVT. A total of 41 kidney transplant patients received a positive duplex ultrasound. The incidence of DVT in our kidney transplant cohort was 4.7%. The most common period of DVT diagnosis was in the perioperative period within the first 4 weeks. A Cohen kappa statistic of -0.02 occurred between the surgical incision site of the kidney transplant and the side of DVT occurrence. Large positive kappa statistic values indicate agreement, whereas large negative values indicate disagreement. Approximately 64.6% of transplant patients with a positive duplex ultrasound had a 1:1 correlation to the side of DVT, although this did not reach statistical significance. There was no statistically significant difference in patient sex, race, or age between the two groups.

Conclusion:

The incidence of symptomatic DVT in this cohort was 4.7%, which is lower than that reported in the literature. DVT was highest during the first four weeks postoperatively. There was an increased rate of ipsilateral DVTs to the kidney transplant, although this did not reach statistical significance. ?

 

81.05 New 5-Factor Frailty Index Can Predict Outcomes in Patients Undergoing Endovascular Aneurysm Repair

Posted on January 31, 2019

V. Pandit1, M. Zeeshan1, S. Jhajj1, A. Lee1, K. R. Goshima1, C. Weinkauf1, W. Zhou1, T. Tan1  1University Of Arizona,Department Of Surgery,Tucson, AZ, USA

Introduction:
The modified frailty index (mFI-11) is a NSQIP-based 11-factor index that has been proven to adequately reflect frailty and predict mortality and morbidity. In past years, certain NSQIP variables have been removed from the database; as of 2015, only 5 of the original 11 factors remained. The predictive power and usefulness of these 5 factors in an index (mFI-5) have not been proven in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). The goal of our study was to compare the mFI-5 to the mFI-11 in terms of value and predictive ability for mortality, postoperative infection, and unplanned 30-day readmission.

Methods:
The mFI was calculated by dividing the number of factors present for a patient by the number of available factors for which there were no missing data. Spearman's rho test was used to assess correlation between the mFI-5 and mFI-11. Predictive models, using both unadjusted and adjusted logistic regressions, were created for each outcome for EVAR using 2005-2012 NSQIP data, the last year all mFI-11 variables existed.

Results:
A total of 14,387 patients were included. Mean age was 71.6±6.5. Overall, 22.1% patients were frail. A total of 24.1% had in-hospital complications, while 4.9% patients died. Correlation between the mFI-5 and mFI-11 was above 0.9 across all outcomes for patients undergoing EVAR. Adjusted and unadjusted models showed similar c-statistics for mFI-5 and mFI-11, and strong predictive ability for mortality, postoperative complications and 30-days readmission (Table 1).

Conclusion:
The mFI-5 and the mFI-11 are equally effective predictors of postoperative outcomes in patients undergoing endovascular aneurysm repair of abdominal aortic aneurysm and the mFI-5 is a strong predictor of postoperative complications, mortality and 30-d readmission. It has credibility for future use to study frailty within the NSQIP database. It also has potential in other databases and for clinical use.
 

81.04 Is Non-ruptured AAA Repair Still a Worthwhile Solution for Nonagenarians?

Posted on January 31, 2019

L. A. Huntress3, J. Kalenik2, V. Dombrovskiy3, S. G. Huang3, R. Shafritz3, S. Rahimi3  2University of Georgia,Athens, GA, USA 3Rutgers RWJMS,Division Of Vascular Surgery,New Brunswick, NJ, USA

Introduction:  The practicality of non-ruptured abdominal aortic aneurysm (AAA) repair in patients aged 90 and above (90+) remains in question.  This study assessed the short-term outcomes of elective endovascular aortic repair (EVAR), and compared them between patients aged 90+ and patients aged 80-89.

Methods: The National Inpatient Sample (NIS) was queried from 2012-2015, and patients aged 80 and above who had undergone elective EVAR were identified. Postoperative complications, hospital mortality, hospital length of stay, and total hospital cost in patients aged 90+ were compared to those aged 80-89 using Chi square test; multivariable logistic regression analysis controlled for age, gender, race, comorbidities, and hospital characteristics; and Wilcoxon rank sum test. Total hospital cost was adjusted to 2015 U.S. dollars.

Results: A total of 26,115 patients were estimated: 24,210 (92.7%) aged 80-89 and 1,905 (7.3%) aged 90+. Compared to octogenarians, patients aged 90+ were more likely to develop postoperative cardiac complications (OR [odds ratio]=1.68; 95%CI [confidence interval] 1.29-2.18), stroke (OR=3.19; 95%CI 1.59-6.39), urinary tract infection (OR=1.39; 95%CI 1.06-1.82), and bleeding (OR=1.41; 95%CI 1.23-1.62), the last of which required more blood transfusions (OR=1.31; 95%CI 1.14-1.52). However, hospital mortality did not differ among both age groups, and no differences in mortality among various races or genders were observed. At the same time, mortality overall in urban teaching and non-teaching hospitals was lower than in rural hospitals (OR=0.37; 95%CI 0.22-0.62 and OR=0.43; 95%CI 0.25-0.74, respectively). Hospital length of stay (median= 2 days, IQR [interquartile range] 1-3 days in both groups) and total hospital cost (median= $27,950; IQR $21,193-36,079 in octogenarians vs median= $27,203; IQR $20,436-36,332 in nonagenarians; P=0.47) did not differ between the two age groups

Conclusion: Although patients aged 90+ are at an increased risk of some postoperative complications following elective EVAR, hospital mortality and hospital resource utilization in this group of patients are not greater than in octogenarians. Elective EVAR should be considered in nonagenarians with non-ruptured abdominal aortic aneurysm.

 

81.03 Hepatoportal Venous Trauma: Analysis of Incidence, Morbidity and Mortality

Posted on January 31, 2019

S. Maithel1, A. Grigorian1, N. Kabutey1, B. Sheehan1, S. Gambhir1, J. Nahmias1  1University Of California – Irvine,Surgery,Orange, CA, USA

Introduction:

Traumatic injuries to the superior mesenteric, portal and hepatic veins are rare with an incidence of roughly 0.1%. However, the mortality rates are high ranging from 45-52.7% for superior mesenteric vein (SMV), 50-70% for portal vein (PV), and 50-100% for hepatic vein (HV) injuries in small previous single center reports. We hypothesize that SMV injury is associated with lower risk of mortality compared to HV and PV injury in adult trauma patients.

Methods:

The Trauma Quality Improvement Program database (2010-2016) was queried for patients with injury to either the SMV, PV, or HV. A multivariable logistic regression model was used for analysis.

Results:

From 1,403,466 patients, 509 patients had SMV injury, 357 patients had PV injury and 255 patients had HV injury. Compared to patients with PV and HV injuries, patients with SMV injuries were older (39 years vs 29 years, p<0.01), had lower injury severity score (25 vs 26, p<0.01), and a lower percentage of severe (grade >3) abbreviated injury scale for abdomen (57.6% vs 72.3%, p<0.01). A higher percentage of SMV injuries were from blunt mechanism compared to portal and hepatic vein injury (60.3% vs 48.1%, p<0.01). Patients with a SMV injury had a longer length of stay (9 days vs 6 days, p=0.01), higher rates of concurrent bowel resection (38.1% vs 9.9%, p<0.01), and lower mortality (36% vs 47.9%, p<0.01) compared to patients with PV and HV injuries. However, after controlling for covariates, traumatic SMV injury increased risk of mortality (OR 2.37, CI=1.55-3.62, p<0.001) in adult trauma patients as did PV injury (OR 3.74, CI=2.29-6.12, p<0.001) and HV injury (OR 3.44, CI=1.95-6.07, p<0.001).

Conclusion:

Traumatic SMV injury is associated with a lower rate of mortality compared to injuries of the HV and PV. SMV injury greater than doubles the risk of mortality in adult trauma patients, whereas HV injury more than triples the risk and portal vein injury nearly quadruples the risk of mortality.

 

81.02 Image Based 3D CT Decreases Radiation Exposure During Fenestrated Endovascular Aortic Aneurysm Repair

Posted on January 31, 2019

H. Weissler1, K. Southerland1, S. Nag1, C. Long1, B. Gilmore1, M. Turner1, L. Olivere1, M. Cox1, C. Shortell1  1Duke University Medical Center,Vascular Surgery,Durham, NC, USA

Introduction: Fenestrated endovascular aortic aneurysm repair (FEVAR) has expanded the benefits of endovascular aortic aneurysm repair (EVAR) to a population of patients who would have otherwise been anatomically unfit for endovascular repair.  However, FEVAR is associated with high radiation doses and contrast loads due to its increased complexity.  Three-dimensional (3D) fusion computed tomography (CT) merges the preoperative CT with intraoperative imaging to create a vascular mask and has been shown to decrease radiation and contrast use during FEVAR.  Currently available 3D fusion systems use hardware-based (i.e. operating table) tracking to position the overlay on the fluoroscopic image.  This is labor intensive and often leads to inaccurate overlays.  Our institution recently implemented a novel, cloud-based 3D fusion system which uses the patient’s vertebral anatomy rather than the operating table to register and create the overlay.  This system has been shown in prior studies to be highly accurate and decrease radiation dose required for EVAR. The purpose of this study was to determine if radiation dose reduction during FEVAR would occur with this new 3D fusion strategy.

Methods:
Our institutional database was reviewed to identify patients who underwent elective FEVAR.  Patients treated using our cloud-based 3D fusion software CT were compared to patients treated in the immediate 6 months prior to the implementation of 3D fusion CT.  Primary end points included patient radiation exposure (mGy), contrast use (mL), and fluoroscopy and procedure times (minutes).

Results:
Thirty-three patients underwent FEVAR from October 2016 through June 2018, twenty prior to implementation of 3D fusion CT and thirteen after. There was no difference between these groups regarding demographics, BMI  or comorbidities. Radiation dose was significantly decreased following 3D fusion CT implementation (5735 ± 2651 mGy versus 3503 ± 2422 mGy, p=0.019).  In addition, there was a significant decrease in the number of FEVARs requiring a high radiation dose (> 2Gy) with 3D fusion CT (9 vs 19, p=0.044).  There was no difference in fluoroscopy time (72.7 ± 16.9 minutes versus 62.9 ± 15.1 minutes, p=0.061), procedure time (257.6 ± 100.1 minutes versus 213.3 ± 41.1 minutes, p=0.118) and contrast volume (94.5 ± 34.7 mL versus 72.8  ± 37.8 mL, p=0.168) between the two groups.

Conclusions:
These results demonstrate that the use of an intraoperative image-based 3D fusion CT strategy based on the patient’s vertebral anatomy rather than hardware can significantly decrease radiation exposure during FEVAR.  Endovascular solutions to aortic pathology will undoubtedly continue to expand; therefore radiation safety will be paramount.  Image based 3D fusion CT has the potential to improve clinical and safety outcomes for both patients and providers.

 

81.01 Incidence and Risk Factors Associated with Ulcer Recurrence among Patients with Diabetic Foot Ulcers

Posted on January 31, 2019

C. J. Abularrage1, J. K. Canner2, N. Mathioudakis3, C. Lippincott4, R. L. Sherman1, C. W. Hicks1  1The Johns Hopkins University School Of Medicine,Division Of Vascular Surgery And Endovascular Therapy,Baltimore, MD, USA 2The Johns Hopkins University School Of Medicine,Department Of Surgery,Baltimore, MD, USA 3The Johns Hopkins University School Of Medicine,Division Of Endocrinology And Metabolism,Baltimore, MD, USA 4The Johns Hopkins University School Of Medicine,Division Of Infectious Diseases,Baltimore, MD, USA

Introduction:

Recent studies demonstrate favorable diabetic foot ulcer (DFU) healing outcomes with the implementation of a multidisciplinary team. However, the long-term outcomes of this approach to DFU care are unknown. We aimed to describe the incidence of and risk factors associated with ulcer recurrence after initial complete healing among a cohort of DFU patients treated in a multidisciplinary setting.

Methods:
All patients presenting to our multidisciplinary diabetic limb preservation service from 6/2012-04/2018 were enrolled in a prospective database. Wounds were classified according to the SVS-WIfI at initial presentation. The incidence of ulcer recurrence after complete wound healing was assessed per limb using the Kaplan Meier method, and a stepwise multivariable Cox proportional hazards model was created to identify independent predictors of ulcer recurrence.

Results:
A total of 244 patients with 304 affected limbs were included. Mean age was 59.2±3.8 years, 62.7% of patients were male, and 61.9% were black. Nearly all (95.1%) of patients has loss of protective sensation, with abnormal proprioception in 23.9%. Ulcer recurrence occurred in 38.5% of limbs at a mean time of 310±30 days. Only 12.8% of recurrent ulcers occurred at the same site as the initial wound. Ulcer recurrence rates at one- and three-years post-healing were 30.6±3.0% and 64.4±5.2%, respectively (Figure), and did not significantly differ by the WIfI stage of the initial wound (P=.34). Recurrent ulcers were smaller (4.4±1.1cm2 vs. 8.2±1.2cm2; P=0.04) and had a lower WIfI stage (stage 4: 7.7% vs. 22.4%; P<0.001) than initial ulcers. Time from ulcer onset to assessment was lower for recurrent ulcers (0.9±0.3 vs. 2.4±0.2 months; P<0.001), and wound healing time was significantly reduced (95.0±9.8 vs. 131.8±7.0 days; P=0.004).  Independent predictors of ulcer recurrence included abnormal proprioception [HR 1.57 (95%CI 1.02-4.43); P=.04] and younger age [HR 1.02 per year (95%CI 1.01-1.04). Patient race, BMI, socioeconomic status, comorbidities, blood sugar control (hemoglobin A1c), and wound location were not independently associated with ulcer recurrence.

Conclusion:
In this prospective cohort of diabetic foot ulcer patients, ulcer recurrence occurred in nearly two-thirds of limbs within three years. Importantly, time to diagnosis and healing was significantly lower for recurrent ulcers, and downstaging was common. These data suggest that engaging DFU patients in a multidisciplinary care model with frequent follow-up and focused patient education may serve to decrease DFU morbidity.

79.10 The Impact of Medicaid Expansion on Utilization of Vascular Procedures and Rates of Amputation

Posted on January 31, 2019

K. G. Bennett1, M. E. Smith1, N. F. Matusko1, J. F. Waljee1, N. H. Osborne1, P. K. Henke1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA

Introduction:
In 2001, the state of New York expanded Medicaid coverage, providing access to care for thousands of previously uninsured patients. Although these policy changes can enhance the opportunity for obtaining care, little is known regarding care utilization, especially amongst patients with vascular disease and critical limb ischemia for whom access to procedures may prevent limb loss. We sought to measure the impact of Medicaid expansion on the rates of total vascular procedures, open procedures, endovascular procedures, and amputations.

Methods:
We examined discharge records from the 1998-2006 State Inpatient Databases of New York (intervention) and Arizona (control). Discharge records of interest were identified using ICD-9 vascular procedure codes. To measure the impact of Medicaid expansion on the rates of total vascular, open vascular, and endovascular procedures, as well as amputations, we used a difference-in-difference analysis to compare the number of procedures performed per admission within each state. We used logistic regression, truncated poisson, and zero-inflated poisson regression to model each outcome while adjusting for relevant patient covariates.

Results:
In this cohort of 112,624 patients undergoing vascular procedures, the difference-in-difference estimator demonstrated that expansion of Medicaid coverage was associated with lower odds of mortality (OR 0.77, p=0.043), but this became insignificant after controlling for patient-level covariates (OR 0.92, p=0.5). The difference-in-difference estimators also demonstrated that Medicaid expansion was associated with lower incidence rate ratios of total vascular procedures (IRR 0.65, p<0.001) and open vascular procedures (IRR 0.92, p=0.002), but a higher incidence rate ratio of endovascular procedures (IRR 1.13, p<0.001). There was no change in the incidence rate ratio of amputations (IRR 1.02, p=0.53). In patients with critical limb ischemia (N =12,668), the difference-in-difference estimators were also significant, demonstrating that expansion was associated with a lower incidence rate ratio of total procedures (IRR 0.59, p<0.001) and endovascular procedures (IRR 0.59, p<0.001) but a higher incidence rate ratio of amputations (IRR 1.43, p=0.001) and higher odds of mortality (OR 2.21, p=0.032).

Conclusion:
After Medicaid expansion, the rates of total vascular procedures decreased, with no impact on amputations rates in New York. Moreover, the utilization of interventions that could prevent amputations in patients with critical limb ischemia did not increase. Thus, while Medicaid expansion may improve access to care, significant barriers and disparities continue to prevent appropriate utilization of limb-saving procedures.
 

79.04 The Influence of Healthcare Resource Availability on Amputation Rates in Texas

Posted on January 31, 2019

J. Cao1, S. Sharath1, N. Zamani1, N. R. Barshes1  1Baylor College Of Medicine,Division Of Vascular Surgery And Endovascular Therapy,Houston, TX, USA

Introduction:  Amputation rates in Texas are high, and racial disparities continue to affect leg amputation rates. Targeted interventions aimed at reducing health disparities may benefit patients in high-need, low-resource areas, and reduce gaps in care.

Methods:  We collated 2005-2009 data on 254 Texas counties from three sources: Texas Inpatient Public Use Data File, Health Resources and Services Administration, and the County Health Rankings and Roadmaps. The primary outcome measure was the number of non-traumatic, lower-extremity amputations. Counties with greater than 11 leg amputations per 100,000 patients per year were designated as “hotspot” counties. Population-adjusted linear and logistic regressions identified factors that could explain increasing amputations among Texas counties.

Results: We identified 33 counties in Texas as “hotspot” counties. Hotspot counties had fewer healthcare resources and lower healthcare utilization. Dual Medicare/Medicaid enrollment and ER visits for foot complications are each associated with more amputations. In the presence of more ER visits, greater dual enrollment decreases total associated amputations (coefficients = -1.21*10-06, P<0.001). In counties with more than 70% rural communities, additional primary care providers decreased the total associated amputations (coefficients = -0.004, P=0.022). Populations in hotspot counties consisted of more people with diabetes (OR = 1.49, P<0.001) and more people categorized as black (OR = 1.09, P=0.007).

Conclusion: Healthcare availability plays a critical role in decreasing PAD-related amputations. Insurance enrollment and improved access to primary care providers may help reduce PAD-associated leg amputations. Strategic resource allocation may promote the reduction in PAD-associated amputations.

 

67.07 Developing Collateral Arteries Unravel Their Internal Elastic Laminae for Diameter Growth

Posted on January 31, 2019

R. M. McEnaney1,2, D. D. McCreary1, E. Tzeng1,2  1VA Pittsburgh Healthcare System,Vascular Surgery,Pittsburgh, PA, USA 2University Of Pittsburgh School of Medicine,Vascular Surgery,Pittsburgh, PA, USA

Introduction:   Collateral artery growth is a natural and sometimes life-preserving response to arterial occlusive disease.  This is because collateral arteries maintain end organ perfusion once a conductance artery becomes occluded.  “Outward remodeling” describes a process of active cellular activity and matrix turnover that expands the vessel diameter.   For outward remodeling to occur, matrix constraints on arterial lumen diameter must be released. These constraints exist due to the matrix structure of an artery. Elastic fibers coalesce to form lamellae and are the major structural elements within the intima and media.  These matrix elements create the elasticity and the luminal topography characteristic of arteries.  However, it is likely that the elastic lamellar structure also creates diameter restraint and must be degraded to achieve outward remodeling.

Methods:   A modified procedure of hind limb ischemia was performed in rats, as per our previously published report.  Animals were euthanized, and collateral artery tissues were harvested at up to 12 weeks and preserved in paraformaldehyde.  Microscopy was performed with an Olympus FluoView MPE Multiphoton microscope with second-harmonic generation to view elastin and collagen structure.

Results:  Striking structural alterations occur along with arterial diameter expansion that are persistent at 12 weeks. (Figure) We observed in collateral vessels which increased diameter up to threefold, a change in the internal elastic lamina from a nearly continuous, wrinkled and fenestrated sheet to a web-like appearance.  Collagen orientation in collateral arteries appears perturbed, with straightening of groups rather than the typical wavy, ribbon-like appearance.

Conclusion:  Outward remodeling is an important vascular adaptation capable of producing functional collateral arteries which are relevant to patients with cardiovascular diseases.  This study shows that during outward remodeling, the normal elastic lamellar structure of an artery becomes irrevocably altered. This also results in a topographical change in the luminal surface of the collateral artery.  Elastic fibers, structural ECM components unique to vertebrates, are integral to the function of the cardiovascular system and require a complex assembly known to occur only in development.  Perhaps more clinically relevant is understanding the mechanisms underlying this elastic remodeling to develop enhanced collateral artery growth for patients with arterial occlusive disease.

 

67.04 ER Stress Increases Susceptibility to Sporadic Aortic Aneurysm and Dissection in Mice

Posted on January 31, 2019

W. Luo1,2, Y. Wang1,2, L. Zhang1,2, P. Ren1,2, C. Zhang1,2, J. Guo1,2, C. Joseph S1,2,3, Y. Shen1,2,3, S. LeMaire1,2,3  1Baylor College Of Medicine,Division Of Cardiothoracic Surgery,Houston, TX, USA 2Texas Heart Institute,Department Of Cardiovascular Surgery,Houston, TX, USA 3Baylor College Of Medicine,Cardiovascular Research Institute,Houston, TX, USA

Introduction: Aortic aneurysm and dissection (AAD) carries significant morbidity and mortality. One of the significant features of AAD is progressive smooth muscle cell (SMC) dysfunction and depletion, which leads to aortic dilatation, biomechanical failure, and ultimately rupture. However, the molecular mechanisms underlying the progressive SMC dysfunction and depletion are poorly understood. Increasing evidence has suggested a critical role of endoplasmic reticulum (ER) stress in cell dysfunction. However, whether ER stress can promote aortic destruction, dysfunction and AAD development is unknown. In this study, we examined the effect of ER stress on aortic destruction and AAD formation in mice.

Methods:  The activation of ER stress was compared in aortic tissues from patients with sporadic ascending thoracic AAD with that in tissues from age-matched organ donor controls. The contribution of ER stress to AAD development was assessed by comparing AAD development in C57BL/6J mice that were given thapsigargin (Tg) (n=39) or vehicle (n=40) before challenged with low-dose angiotensin infusion (AngII, 1000 ng/min/kg) for four weeks. 

Results: We observed significant upregulation of ER stress markers in patient aortic tissues, especially in smooth muscle cell (SMC). Thapsigargin itself did not cause AAD or dilatation. However, thapsigargin significantly increased the challenge-induced incidence of AAD (15% in challenged mice vs 44% in Tg treated challenged mice, p=0.005), severe AAD (8% in challenged mice vs 23% in Tg treated challenged mice, p=0.05). Thapsigargin showed similar effect in male and female mice. Furthermore, aortic tissues from challenged mice treated with Tg showed markedly increased aortic destruction and elastic fiber fragmentation.

Conclusion: Our findings demonstrate that inducing ER stress with thapsigargin increases susceptibility to sporadic aortic aneurysm and dissection in mice. 

 

67.03 Histone Methylation Directs Macrophage Toll-like Receptor 4 Expression and Regulates Wound Healing

Posted on January 31, 2019

F. M. Davis1, A. Kimball1, A. Joshi1, A. DenDekker1, A. Obi1, K. Singer2, B. Moore3, S. Kunkel4, K. Gallagher1  2University Of Michigan,Pediatric Endocrinology,Ann Arbor, MI, USA 3University Of Michigan,Microbiology And Immunology,Ann Arbor, MI, USA 4University of Michigan,Pathology,Ann Arbor, MI, USA 1University of Michigan,Surgery,Ann Arbor, MI, USA

Introduction:  Macrophages (MΦ) are critical for both the initiation and resolution of the inflammatory phase of wound repair.  Toll-like receptors (TLRs), particularly TLR4, play a critical role in regulating macrophage-mediated inflammation and tissue regeneration. Since an initial inflammatory phase is vital for tissue repair, we hypothesized that TLR4 regulates macrophage-mediated inflammation in wound repair.

Methods:  Using a murine wound healing model, percent wound healing was analyzed between control and TLR4 deficient (TLR4-/-) mice (n= 10/group).  Bone marrow-derived macrophages (BMDMs) were isolated and cultured in standard fashion. Expression of inflammatory genes (IL1β, IL12, TNFα) were determined by qPCR. Chromatin immunoprecipitation was used to analyze H3K4 methylation.  Adoptive transfer was performed with intravenous injection of CD11b+ cells isolated from spleens of control and TLR4-/- mice. Statistical significance was determined using Student t-tests or ANOVA.

Results: TLR4 expression in wound MΦs was significantly increased throughout the wound healing course (p<0.05).  We identified that changes in MΦ TLR4 during the course of wound healing correlated with increased expression of the histone methyltransferase Mix-lineage leukemia-1 (MLL1) and its activating epigenetic marker, histone 3 lysine 4 tri-methylation (H3K4me3), on the TLR4 promoter. Mice deficient in TLR4 demonstrated delayed wound healing at all time points post-injury. Furthermore, in vitro BMDMs and in vivo wound macrophages isolated from TLR4-/- wounds had decreased inflammatory cytokine production (p<0.05). Importantly, adoptive transfer of monocyte/macrophages from wild-type mice restored normal healing in the TLR4-/- mice.  

Conclusion: These results define a role for macrophage specific TLR4 in the inflammatory response following cutaneous tissue injury and suggest that MLL1 regulates TLR4 expression in wound MΦs.

 

67.01 Encapsulation Of Arteriogenic Macrophages Enhances Cell Retention And Ischaemic Limb Perfusion

Posted on January 31, 2019

F. E. Ludwinski1, G. Damodaran1, A. S. Patel1, J. Cho1, S. Jayasinghe2, A. Smith1, B. Modarai1  1King’s College London School Of Medicine,School Of Cardiovascular And Medical Sciences,London, London, United Kingdom 2University College London,Department Of Mechanical Engineering,London, LONDON, United Kingdom

Introduction:
Cell therapy has been proposed as a means of improving perfusion of ischaemic limbs. Direct injection of pro-angiogenic cells has, however, shown only modest outcomes in clinical trials, perhaps because of their loss from the site of injection. Here, we investigate alginate microsphere encapsulation as a means of enhancing retention and improving reperfusion of the ischaemic hindlimb.

Methods:
150μm sodium alginate microspheres, containing 108cells/ml of Tie2-expressing murine bone marrow-derived macrophages (eTie2-iBMMs), were generated using a clinical-grade cell encapsulator. Comparisons were made between eTie2-iBMMs and non-encapsulated cells (nTie2-iBMMs), with respect to: cell viability and phenotype; in vitro pro-angiogenic function after angiopoietin-mediated stimulation of Tie2 (VEGF expression and endothelial tubule formation); cell retention (IVIS biofluorescent imaging); and ability to promote revascularisation in the ischaemic murine hindlimb.

Results:
Encapsulation did not affect Tie2-iBMM viability or phenotype up to 7days in vitro, the expression of VEGF, or formation of endothelial tubules (p=>0.05), although stimulated eTie2-iBMMs secreted significantly greater levels of MCP-1 (p=0.0022). Cell retention was significantly enhanced in ischaemic murine hindlimbs treated with eTie2-iBMMs (p=0.0083) and this was associated with significantly greater limb perfusion over 21 days (p=0.0005).

Conclusion:
Alginate encapsulation of pro-arteriogenic macrophages is not detrimental to their viability or phenotype, and increases their retention and regenerative capacity in the ischaemic hindlimb. Translation of this methodology to a clinical setting may enhance the efficacy of novel cell-based therapies for the treatment of CLI.
 

58.02 Frailty Severity Predicts Poor Outcome After First-time Lower Extremity Revascularization

Posted on January 31, 2019

L. Gonzalez1,2, M. Kassem1,2, A. Owora3, S. Cardounell1, M. Monita1, S. Brangman1, V. Gahtan1,2  1State University Of New York Upstate Medical University,Vascular And Endovascular Surgery,Syracuse, NY, USA 2Syracuse VA Medical Center,Surgery,Syracuse, NY, USA 3Syracuse University,Falk College School Of Public Health,Syracuse, NY, USA

Introduction:  Frailty severity is a predictor of poor outcome after vascular surgery. The modified frailty index (mFI) has been validated as a prognostic assessment tool in large scale databases of patients with peripheral arterial disease. Our objectives were to determine the predictive utility of the mFI after first-time lower extremity revascularization and to identify biomarkers of frailty in patients with peripheral arterial disease. Hypotheses: (1) frailty severity is associated with adverse outcome after revascularization and (2) select preoperative data may serve as biomarkers of frailty.

Methods:  A retrospective cohort study was performed of all first-time revascularizations [open surgery (OS) and endovascular surgery (ES)] in male veterans at a single institution (2003-2016). Multivariable logistic and Cox proportional hazard regression models were used to examine the relationship between the mFI and post-operative short-term (30-day morbidity, readmission, and re-intervention) and long-term (up to 2-year incidence of re-intervention, amputation, or mortality) outcomes, respectively. 

Results: 431 patients met inclusion criteria (OS n=188; ES n=243), with a mean age of 66±9 years and median follow up of 16 months. Treatment groups were similar in baseline characteristics, pre-operative lab values, and polypharmacy tallies. Mean mFI was 0.39±0.16 for the OS group and0.38±0.15 for the ES group (p=0.43). 30-day complications (aOR 4.89; 95%CI: 1.67-14.33) and early readmissions (aHR 3.32; 95%CI: 1.16-9.55) were increased in the OS group compared to the ES group. Frailty severity did not predict risk of re-intervention in either group.  Kaplan Meier analysis showed an increased risk of amputation, death, and the composite outcome of amputation and/or death in both treatment groups with increasing frailty when stratified by frailty severity (p<0.005 for all).  Multivariate analysis confirms that frailty independently predicts major amputation (aHR 2.16; 1.06-4.39), mortality (aHR 2.62; 95%CI: 1.17-5.88), and the composite outcome (aHR 1.97; 95%CI: 1.06-3.68) in the cohort as a whole. Hypoalbuminemia is correlated with increased mFI in the ES group (p<0.01), but only showed a trend with mFI in the OS group (p>0.05).  Independent of treatment assignment and preoperative mFI, higher albumin concentration was associated with lower risk of amputation (aHR: 0.58; 95% CI: 0.36 -0.94) and mortality (aHR: 0.45; 95% CI: 0.25-0.83). Higher hemoglobin concentration was also independently predictive of limb salvage (aHR 0.72 95%CI: 0.62-0.84).

Conclusion: Frailty severity is predictive of short- and long-term outcomes after lower extremity revascularization. Hypoalbuminemia and anemia are associated with higher mFI and independently predicted poor outcome after revascularization, suggesting albumin and hemoglobin concentration may serve as true biomarkers of frailty in this population. 
 

58.01 Older Age Increases Mortality And Stroke Risk at One Year After Carotid Revascularization

Posted on January 31, 2019

S. J. Aitken1,2, S. J. Aitken1,2  1Concord Repatriation General Hospital,Institute Academic Surgery (Vascular),Sydney, NEW SOUTH WALES (NSW), Australia 2University Of Sydney,Concord Clinical School,Sydney, NSW, Australia

Introduction:
Cardiac and neurological complications following carotid revascularization have been associated with an increased risk of mortality, especially in older patients. This study reports mortality and stroke following carotid revascularization in Australia, comparing outcomes up to 1 year for those with and without complications within 30days and in younger and older patients.

Methods:
Routinely collected hospital data on all patients in New South Wales (NSW), Australia, were linked to state-wide mortality records. All patients who underwent carotid revascularization (endarterectomy or stenting) between 2010-2012 were selected. Primary outcomes of mortality or stroke were measured at 30days, 90days and 1 year. Secondary outcomes were complications within 30days, length of stay and hospital readmission within 90days. Differences in outcomes between younger (aged less than 75 years old) and older (aged 75 years and older) patients were evaluated. Complications were assessed at 30days, including stroke and major adverse cardiac events (MACE). Outcomes were assessed with multivariable Cox regression and Kaplan Meier survival analysis.

Results:

3008 carotid revascularization procedures were performed between 2010 and 2013; 20% for symptomatic carotid disease (n=598). Carotid endarterectomy was the most common procedure (n=2280, 76%), with 728 patients (24%) having carotid stenting. The median age was 72 years (SD 10), with more males than females having carotid revascularization (M:F ratio 69%:31%).  Mortality at 30days was 0.8% (n=26), 90days 1.4% (n=43) and 1 year 3.9% (n=112). Postoperative stroke occurred in 14 patients at 30days (0.5%), 90days 1.1% (n=32) and 1 year 1.7% (n=52).  17.3% of patients had a major complication within 30days (n=522). Median length of stay was 3 days (IQR 7). 25% of patients (n=754) had a readmission for any cause at 90days. After adjusting for age, gender and procedure type, patients aged 75 years or older were at higher mortality risk than younger patients (HR 2.7, 95%CI 2.2-3.3, P<.0001) at 1 year. After adjusting for age, gender and procedure type, older patients had a higher risk of stroke at 1 year (HR 2.4, 95%CI 1.9-2.8, P<.0001) than younger patients. Stroke risk was also associated with carotid stenting and major complications.   MACE occurring within 30days predicted 1 year stroke (HR 2.1, 95%CI 1.6-2.9, P<.0001) and death (HR 2.0, 95%CI 1.5-2.7, P<.0001). Older patients had a higher incidence of MACE (IRR 1.9, 95%CI 1.4-2.6, P<.0001) and complications (IRR 1.2, 95%CI 1.1-1.4, P.007) within 30days than younger patients.

Conclusion:

Older age increased risk for all adverse outcomes including mortality, stroke, complications, increased length of stay and readmission. Postoperative complications also increased the risk of mortality and stroke at 1 year. Targeted strategies to improve perioperative care in older patients are required to reduce complications associated with postoperative mortality.

56.08 Variable Management Preferences in the Treatment of Lower Extremity Prosthetic Graft Infections

Posted on January 31, 2019

N. Zamani1, S. E. Sharath1, P. Kougias1  1Baylor College of Medicine / Michael E. DeBakey VA Medical Center,Division Of Vascular Surgery And Endovascular Therapy, Michael E. DeBakey Department Of Surgery,Houston, TX, USA

Introduction: Lower extremity prosthetic graft infections continue to be serious postoperative complications. Though complete graft excision with extra-anatomic bypass has traditionally been required, graft preservation techniques have been proposed for select patients in order to avoid the physiologic demand of such a reconstruction. We aimed to assess the attitudes of practicing surgeons regarding their preferred management strategy and their perceptions about which operative technique results in the most favorable long-term outcomes.

Methods:  A voluntary, anonymous, cross-sectional survey was administered to actively practicing members of the Society for Clinical Vascular Surgery (SCVS) in the United States. Surgeons were asked to: (1) rank the factors that influence their management strategy, (2) choose between graft excision or preservation in a standard clinical scenario, and (3) identify the most effective strategy for promoting long-term limb preservation.

Results: Ninety (19%) licensed surgeons participated in the survey.  The three factors that were most influential in determining the management of lower extremity prosthetic graft infections were: the presence of sepsis, involvement of an anastomosis, and the presence of Pseudomonas. Conversely, the three least influential factors were: operating room availability, projected length of stay, and prosthetic graft material (Figure 1). In a stable, non-septic patient, 67% (n = 60) of respondents most frequently excise the graft. A form of preservation, however, was the preferred management strategy in 31% (28) of instances, with 20% (18) of all surgeons using antibiotic beads as their preferred method of graft preservation. In assessing the operative strategy associated with the greatest long-term limb preservation rates, 52% (47) of surgeons believed that excision provides the best limb outcomes, while 29% (26) identified preservation as the preferred overall strategy. The remainder (19%) felt that there was probably no difference in the outcomes of these two approaches. Interestingly, of those that prefer to excise the graft, 15% (9/60) actually believed that preservation with antibiotic beads may be the more beneficial therapeutic option.

Conclusion: Substantial discrepancy exists among providers regarding their personal management of lower extremity graft infections and their perception of which operative strategy is ultimately associated with higher rates of limb salvage. Given the range of personal, clinical, and institutional factors that influence a surgeon’s preferred operative approach, a well-designed study is required to definitively address this issue and inform clinical practice.

 

28.10 EphB4 regulates mechanical properties of mouse arteriovenous fistulae

Posted on January 31, 2019

S. Lee1, K. Brownson1, R. Khosravi1, K. Goldstein1, T. Isaji1, J. Humphrey1, A. Dardik1  1Yale University School Of Medicine,New Haven, CT, USA

Introduction:
Veins are typically thin-walled and compliant at low pressures, optimal for their dual roles as conduits for blood returning to the heart and reservoirs for holding most of the blood volume. Surgically connecting a vein to the arterial system as an arteriovenous fistula (AVF) exposes the vein to higher pressure, flow magnitudes and frequencies, triggering a set of molecular pathways that result in venous remodeling, such as dilatation and thickening.  Recent work showed that the venous identity marker EphB4 is upregulated and required for the venous remodeling that occurs during AVF maturation.  However, it is not known how EphB4 function or fistula creation affects the mechanical properties of veins; we hypothesize that increased EphB4 function during fistula remodeling enhances venous compliance.

Methods:
C57BL/6 wild type (WT) and Ephb4+/- (heterozygous) mice were treated with sham surgery or abdominal aortocaval fistulae creation via needle puncture (n=4-6 per group). The thoracic IVC were harvested at post-operative day 21 for uniaxial mechanical testing and subsequent histology. Veins were axially stretched to their in vivo length, then cyclically distended from 1 to ~20 mmHg with phosphate buffered saline while simultaneously recording outer diameter with a side-mounted video camera. Compliance was calculated as the change in cross-sectional luminal area per unit pressure. Veins were sectioned at 5 μm with wall (intima-media) thickness measured manually. Statistical analyses were performed with one-way ANOVA, using the Tukey post-hoc test for multiple comparisons.

Results:
WT AVF distended to a greater maximal diameter compared to WT control veins (1290±35μm vs. 986±55μm; p = 0.04). Similarly, Ephb4+/- AVF distended to a greater diameter compared to Ephb4+/- control veins (1231±75μm vs. 878±77μm, p = 0.007). At physiologic venous pressures (0-5 mmHg), Ephb4+/- veins were less compliant than WT veins (<ΔCWT,EphB4> = -0.05 mm2/mmHg, p = 0.015). Veins became more compliant with fistula creation in both WT (<ΔCWT,F> = 0.17 mm2/mmHg, p = 0.01) and Ephb4+/- (<ΔCEphB4,F> = 0.12 mm2/mmHg, p = 0.006) mice, with Ephb4+/- fistulae remaining less compliant than WT fistulae (<ΔCEphB4F,WTF> = 0.1 mm2/mmHg, p = 0.01). Ephb4+/- veins were significantly thicker than WT veins with (73.2±5.9μm vs 41.9±1.6μm, p = 0.03) or without (81.5±12μm vs 46.3±4.5μm, p = 0.01) fistula creation. 

Conclusion:
Although creation of an AVF results in more distensible and circumferentially compliant veins in both WT and Ephb4+/- mice, veins from Ephb4+/- mice are thicker and stiffer than veins in WT mice both at baseline and after AVF creation.  These results suggest that the structural changes of EphB4-regulated venous remodeling are accompanied by functional changes that support venous adaptation to the fistula environment.

28.09 The Inhibition of Wnt Signaling Attenuates RANKL-induced Osteoclastogenic Macrophage Activation

Posted on January 31, 2019

K. Igari1, M. J. Kelly1, B. Darwich1, D. Yamanouchi1  1University Of Wisconsin,Division Of Vascular Surgery, Department Of Surgery,Madison, WI, USA

Introduction:
We have previously reported the role of osteoclastogenic macrophage activation in abdominal aortic aneurysms (AAAs). Previous reports indicated Wnt signaling has the dual effect of proliferation and differentiation during osteoclatogenesis. Wnt/β-Catenin pathway is a critical regulator of cell pluripotency, cell survival, and cell fate decision in both embryos and adults. The inhibition of β-catenin suppressed proliferation but induced differentiation of osteoclast precursor cells. The aim of this study is to examine the effect of the Wnt signaling inhibitor, ICG-001, under the hypothesis that ICG-001 inhibits osteoclastogenesis through the inhibition of proliferation without induction of differentiation.

Methods:
RAW 264.7 macrophages were stimulated with soluble receptor activator of NF-kB ligand (RANKL) (30ng/ml) to induce the osteoclastogenesis. To examine the effect of the inhibition of the CBP co-activator in Wnt signaling, macrophages were treated with or without ICG-001 (10mM) during RANKL stimulation. The activation and differentiation of macrophages were examined by western blotting, quantitative PCR, and tartrate-resistant acid phosphate (TRAP) staining in vitro. Data are reported as the means ± standard deviation. P values less than 0.05 were accepted as statistically significant.

Results:
The relative expression level of protein of nuclear factor of activated T-cells cytoplasmic 1, a key transcription factor during osteoclastogeneis, was significantly suppressed by ICG-001 treatment compared to the non-treated group (4.46±0.74 versus 7.13±0.50, P < 0.05). Even though there was not a statistically significant difference in TRAP expression between the ICG-001 treated group and non-treated group (1.78±0.55 versus 2.35±0.38, P = 0.24), we showed the trend that ICG-001 decreased TRAP protein expression. Furthermore, the expression of cathepsin K was significantly suppressed in the ICG-001 treated group compared to the non-treated group (4.62±1.60 versus 12.2±1.73, P < 0.05). The relative expression levels of mRNA of TRAP, cathepsin K, and matrix metalloproteinase-9, were significantly lower in the ICG-001 treated group compared to the non-treated group (72.4±5.3 versus 167.1±5.6, P < 0.05, 38.6±7.2 versus 149.3±14.3, P < 0.05, and 175.5±10.5 versus 323.6±70.0, P < 0.05, respectively). Furthermore, TRAP-staining demonstrated the suppressive effect of ICG-001 on osteoclastogenesis. The number of TRAP-positive decreased in the ICG-001 treated group relative to the non-treated group (24.4±7.0 versus 131.2±19.4, P < 0.05).

Conclusion:
The inhibition of Wnt signaling pathway via ICG-001 suppressed osteoclastogenic macrophage activation. Our previous studies showed the importance of osteoclastogenic macrophage activation in AAA, therefore, further studies to examine the therapeutic potential of ICG-001 on AAA are warranted.
 

28.08 The Pro-Resolving Lipid Mediator Maresin 1 (MaR1) Attenuates Abdominal Aortic Aneurysm Formation

Posted on January 31, 2019

C. T. Elder1, G. Lu1, G. Su1, A. K. Sharma1, A. Mast1, G. R. Upchurch1  1University Of Florida,Department Of Surgery,Gainesville, FL, USA

Introduction:  Formation of abdominal aortic aneurysms (AAA) is a multifactorial process and is characterized by inflammation of the aortic wall. Maresin 1 (MaR1) is an endogenous pro-resolving lipid mediator derived from docosahexanoic acid, an ω-3 polyunsaturated fatty acid, and is involved in the resolution phase of acute inflammation. We hypothesized that treatment with exogenous MaR1 would attenuate experimental murine AAA formation.

Methods:  Abdominal aortic aneurysms were induced in C57BL/6 (wild-type; WT) mice (n=4 per group) using an established topical elastase model. Mice were treated with MaR1 (100 ng/mouse for each dose) or vehicle via intraperitoneal injection on days 1, 3, 5, and 7 post AAA induction. On day 14, abdominal aortas were harvested for phenotypic evaluation. 

Results:  Mean abdominal aortic dilation was 131% ± 16 for vehicle treated mice as compared to 88% ± 7 for MaR1 treated mice (p = 0.003). Decreased inflammatory changes were noted on gross phenotypic examination for MaR1 treated mice as compared to vehicle treated mice. 

Conclusion:  The present results demonstrate that systemic administration of MaR1 attenuates abdominal aortic aneurysm formation in mice. Decreased inflammatory phenotypic changes suggest this attenuation is mediated through the pro-resolving effects of MaR1 and represent a potential future target in the treatment of AAA. 

 

28.07 CCR2 Targeted PET Imaging of Rodent Abdominal Aortic Aneurysms Stimulated to Rupture

Posted on January 31, 2019

S. E. Sastriques Dunlop1, S. J. English1  1Washington University,Surgery,St. Louis, MO, USA

Introduction:  Abdominal aortic aneurysm (AAA) development is common in the aging population, and AAA rupture is associated with high mortality. Indications for surgical intervention and AAA rupture prediction rely on antiquated aortic diameter criteria. AAA development is characterized by destructive remodeling of the aortic extra cellular matrix, in part by mononuclear phagocytes. Previous work suggests that the monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis plays an important role in AAA development. We sought to evaluate if increased rat AAA uptake of 64Cu-DOTA-ECL1i, a radiolabeled CCR2 binding peptide under current clinical evaluation, by positron emission tomography (PET) imaging, is predictive of subsequent AAA rupture.

Methods:  ECL1i was conjugated to a DOTA chelator and radiolabeled with 64Cu. 64Cu-DOTA-ECL1i biodistribution analysis was performed in male Sprague-Dawley (SD) rats (N = 4). Utilizing the porcine pancreatic elastase (PPE) exposure model, infrarenal abdominal aortas of male SD rats were exposed to active PPE to induce AAA formation, and each animal received b-aminopropionitrile (BAPN, N = 8) to stimulate AAA rupture. PET imaging was performed at 6 days post AAA induction, and AAA uptake was quantified by mean standardized uptake values (SUVmean). AAA radiotracer uptake was confirmed by ex vivo autoradiography after PET imaging. Immunohistochemistry and RT-PCR were also utilized to identify CCR2 in AAA tissue.  

Results: Biodistribution analysis demonstrated rapid renal clearance of 64Cu-DOTA-ECL1i, with less than 0.5% ID/g in blood 1 hour post intravenous via tail vein injection. PET imaging demonstrated tracer uptake by AAAs that subsequently ruptured (RAAA, N = 5), as well as those AAAs that did not rupture (NRAAA, N = 3). See Figure. RAAAs demonstrated greater 64Cu-DOTA-ECL1i uptake (SUVmean 0.75±0.05) than NRAAAs (SUV mean 0.67 ± 0.05) (p = 0.07). Ex vivo autoradiography confirmed 64Cu-DOTA-ECL1i uptake in each case; while immunohistochemistry and RT-PCR demonstrated upregulation of the CCR2 receptor in each case as well.

Conclusion: CCR2 targeted 64Cu-DOTA-ECL1i PET imaging demonstrated inflammation associated with rat AAA development. Increased radiotracer uptake by AAAs that subsequently ruptured warrants further study to determine the ability of 64Cu-DOTA-ECL1i PET imaging to aid in assessing AAA rupture potential associated with our model, as well as for patients.

 

28.06 Nitric oxide in extracorporeal circulation preserves platelet function as measured by microparticles

Posted on January 31, 2019

T. R. Bellomo1, M. Jeakle1, T. Major1, M. Meyerhoff2, R. H. Bartlett1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 2University Of Michigan,Department Of Chemistry,Ann Arbor, MI, USA

Background: Clotting, anticoagulation, platelet consumption, and poor platelet function are major factors in clinical extracorporeal circulation (ECC). We have shown that Nitric Oxide releasing coatings (NOReL) prevents thrombosis in a rabbit model of ECC without systemic anticoagulation. NOReL prevents platelet adhesion and activation, resulting in preserved platelet count and function. Previous work has shown that activated platelets form platelet-derived microparticles (PMPs). These experiments were designed to determine if PMPs can identify platelet function during ECC.

Objective: The objective of this study is to investigate the effects of NOReL on platelet activation and PMP formation during ECC.

Methods: Uncoated and NOReL coated ECCs were tested in a 4-hour rabbit thrombogenicity model without systemic anticoagulation. Before and after ECC exposure, platelets were stimulated with collagen and PMPs were measured using flow cytometry. 

Results: The uncoated ECCs clotted within the first hour, while the NOReL coated ECCs circulated for 4 hours. Pre ECC exposure, platelets stimulated with collagen produced PMPs. Post ECC exposure, platelets from uncoated circuits generated less PMPs than baseline (186 ± 123 uncoated baseline vs.-131 ± 311 uncoated post circuit) when stimulated with collagen.  However, platelets from the NOReL circuit generated the same amount of PMPs as baseline values (74 ± 61 NOReL baseline vs. 56 ± 118 NOReL post circuit).

Conclusions: Blood exposure during ECC results in platelet activation and clotting. The remaining circulating platelets have lost function, as demonstrated by the low PMP formation in response to collagen. NOReL coated ECCs prevent platelet activation and clotting. In addition, function of the circulating platelets was preserved, as demonstrated by PMP formation in response to collagen. These results indicate that PMPs may be an important measure of platelet activation during ECC. PMPs may provide a simplified way to measure platelet function during clinical ECC.

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