Faculty Bibliography

Publisher: Abstract available from the publisher. OABL- tur

OBJECTIVE: Face transplantation replaces substantial defects with anatomically identical donor tissues; preoperative vascular assessment relies on noninvasive imaging to separate and characterize the external carotid vessels and branches. The objective is to describe and illustrate vascular considerations for face transplantation candidates. METHODS: Novel noninvasive imaging using computed tomography and magnetic resonance imaging over 3 spatial dimensions plus time was developed and tested in 4 face transplant candidates. Precontrast images assessed bones and underlying metal. Contrast media was used to delineate and separate arteries from veins. For computed tomography, acquisition over multiple time points enabled the computation of tissue perfusion metrics. Time-resolved magnetic resonance angiography was performed to separate arterial and venous phases. RESULTS: The range of circulation times for the external carotid system was 6 to 14 seconds from arterial blush to loss of venous enhancement. Precontrast imaging provided a roadmap of bones and metal. Among the 4 patients, 3 had surgical clips, metal implants, or both within 1 cm of major vessels considered for surgery. Contrast-enhanced wide area detector computed tomographic data acquired in the axial mode separated these structures and provided arterial and venous images for planning the surgical anastomoses. Magnetic resonance imaging was able to distinguish between the large vessels from the external carotid systems. CONCLUSIONS: Vascular imaging maps are challenging in face transplantation because of the rapid circulation times and artifact from the initial injury, prior reconstructive attempts, or both. Nevertheless, face transplant candidates require high spatial and temporal resolution vascular imaging to determine those vessels appropriate for surgical anastomoses.

PURPOSE: The maturation of an arteriovenous fistula (AVF) requires remodeling of the arterial inflow and the venous outflow limbs to sustain flows sufficient to support hemodialysis. However, factors influencing remodeling of AVF are poorly understood. We hypothesized that AVF remodeling was an endothelium-dependent process. METHODS: This is a prospective cohort study of patients (n=25) undergoing autologous AVF formation. Brachial artery vasoreactivity studies were performed pre-operatively to assess endothelium-dependent, flow-mediated vasodilation (FMD). High-resolution ultrasound was used to assess venous and arterial diameters intraoperatively, and at 3 months. RESULTS: The mean age was 64.5 +/- 13.6 yrs. Twelve patients (48%) had diabetes. The mean FMD for the entire cohort was (mean +/- SEM) 5.82 +/- 0.9%, (range) 0-17.3%. The vein increased in size 3.19 +/- .28 to 6.11 +/- .41 mm, 108.4 +/- 17.9%, p=.0001, while the artery increased from 3.29 +/- .14 to 4.48 +/- .30 mm, 20.47 +/- 10.8%, p=.013. There was a significant positive correlation between the degree of arterial and venous remodeling, r=.52, p=.023. Brachial artery FMD most strongly correlated with the magnitude of arterial remodeling, r=.47, p=.038. Patients with diabetes failed to undergo venous remodeling to the same extent as did those without diabetes, 59.2 +/- 24.4% vs. 141.5 +/- 25.4%, p=.04. CONCLUSION: Impairment of endothelial function is associated with decreased arterial remodeling and final venous lumen diameter attained at 3 months. Further investigation is needed to determine whether modulation of endothelial function in this cohort can improve AVF maturation.

OBJECTIVE: As in arteries, venous endothelium modulates vessel homeostasis and tone. The effect of an arterialized environment on venous endothelial function remains poorly understood. In particular, regulation of saphenous vein graft (SVG) blood flow and lumen caliber remains undefined. We hypothesized that mature SVGs would exhibit endothelium-dependent, flow-mediated vasodilation (FMD). We further hypothesized that endothelium-derived nitric oxide (NO) was an important mediator. METHODS: Patients with femoral to popliteal artery SVGs that had maintained primary patency and were at least 1 year from surgery were enrolled. High-resolution, B-mode ultrasound scans were used to measure vein graft diameter before and 1 minute after reactive hyperemia (RH) to determine FMD. RH was created through application of 220 mm Hg to the calf for 5 minutes with a sphygmomanometric cuff. After a 10-minute recovery period, nitroglycerin-mediated, endothelium-independent vasodilation was measured 3 minutes after administration of nitroglycerin 0.4 mg sublingually. Brachial artery FMD was determined by validated techniques. L-N(G)monomethyl arginine (L-NMMA; 1 mg/kg infusion over 10 minutes) was used in a subset of patients (n = 6) to competitively inhibit endothelial NO synthase. RESULTS: Nineteen subjects were enrolled. The median age of the SVGs was 34.6 (21.0-49.7) months. SVG flow-mediated, endothelium-dependent vasodilation was measured at 5.28% +/- 3.1% mean change in lumen diameter (range, 1.99%-9.36%; P < .0001 for diameter change). Nitroglycerin-mediated vasodilation was 3.7% +/- 1.0%, (range, 16%-10.04%; P < .005). Intravenous administration of L-NMMA abolished SVG FMD (5.7 +/- 1.4% before L-NMMA vs 0.01 +/- 0.01% during L-NMMA infusion; P = .0088) and attenuated brachial artery FMD (7.54% +/- 1.0% vs 5.7 +/- 1.4; P = .05). CONCLUSION: SVGs manifest flow-mediated, endothelium-dependent, and nitroglycerin-mediated endothelium-independent vasodilation. Vein graft endothelium-dependent FMD is likely mediated by NO. Further investigation will be required to determine the role of endothelial function in vein graft patency.

BACKGROUND: The remodeling of vein bypass grafts after arterialization is incompletely understood. We have previously shown that significant outward lumen remodeling occurs during the first month of implantation, but the magnitude of this response is highly variable. We sought to examine the hypothesis that systemic inflammation influences this early remodeling response. METHODS: A prospective observational study was done of 75 patients undergoing lower extremity bypass using autogenous vein. Graft remodeling was assessed using a combination of ultrasound imaging and two-dimensional high-resolution magnetic resonance imaging. RESULTS: The vein graft lumen diameter change from 0 to 1 month (22.7% median increase) was positively correlated with initial shear stress (P = .016), but this shear-dependent response was disrupted in subjects with an elevated baseline high-sensitivity C-reactive protein (hsCRP) level of >5 mg/L. Despite similar vein diameter and shear stress at implantation, grafts in the elevated hsCRP group demonstrated less positive remodeling from 0 to 1 month (13.5% vs 40.9%, P = .0072). By regression analysis, the natural logarithm of hsCRP was inversely correlated with 0- to 1-month lumen diameter change (P = .018). Statin therapy (beta = 23.1, P = .037), hsCRP (beta = -29.7, P = .006), and initial shear stress (beta = .85, P = .003) were independently correlated with early vein graft remodeling. In contrast, wall thickness at 1 month was not different between hsCRP risk groups. Grafts in the high hsCRP group tended to be stiffer at 1 month, as reflected by a higher calculated elastic modulus (E = 50.4 vs 25.1 Mdynes/cm2, P = .07). CONCLUSIONS: Early positive remodeling of vein grafts is a shear-dependent response that is modulated by systemic inflammation. These data suggest that baseline inflammation influences vein graft healing, and therefore, inflammation may be a relevant therapeutic target to improve early vein graft adaptation.

BACKGROUND: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated to the vascular responses. METHODS: Eighty-eight independent, community-dwelling older adults (70.02+7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-d ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. RESULTS: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. CONCLUSIONS: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

The restenosis rates of 5% to 15% have been reported after carotid endarterectomy (CEA). We undertook this investigation to determine whether the routine practice of carotid artery patch closure and intraoperative completion duplex ultrasonography would result in lower rates of carotid restenosis after CEA. All consecutive carotid endarterectomies performed between 2000 and 2004 at a single institution were reviewed retrospectively. Patients underwent CEA using a longitudinal arteriotomy, followed by routine patching and intraoperative completion duplex ultrasonography. Only patients with at least one postoperative duplex scan performed at a minimum of 180 days after CEA were included. During the 5-year study period, 407 consecutive carotid endarterectomies were performed, with a combined 30-day stroke and mortality rate of 2.5%; 217 patients (53%) had one or more duplex ultrasound examinations performed at least 180 days after CEA. The mean follow-up duration was 692 days. Of the patients who underwent intraoperative intervention based on the results of the completion duplex study, none experienced restenosis, stroke, or death. CEA that is performed with routine patching and intraoperative duplex completion ultrasonography is a safe, durable operation with restenosis rates below those commonly reported.