Gilbert R. Upchurch

Homocyst(e)ine Decreases Bioavailable Nitric Oxide by a Mechanism Involving Glutathione Peroxidase

Hyperhomocyst(e)inemia is believed to injure endothelial cells in vivo through a number of mechanisms, including the generation of hydrogen peroxide (H2O2). Earlier in vitro studies demonstrated that homocyst(e)ine (Hcy) decreases the biological activity of endothelium-derived relaxing factor and that this decrease can be reversed by preventing the generation of hydrogen peroxide. Here we show that Hcy treatment of bovine aortic endothelial cells leads to a dose-dependent decrease in NO x (p = 0.001 by one-way analysis of variance) independent of endothelial nitric-oxide synthase activity or protein levels and nos3 transcription, suggesting that Hcy affects the bioavailability of NO, not its production. We hypothesized that, in addition to increasing the generation of H2O2, Hcy decreases the cell’s ability to detoxify H2O2 by impairing intracellular antioxidant enzymes, specifically the intracellular isoform of glutathione peroxidase (GPx). To test this hypothesis, confluent bovine aortic endothelial cells were treated with a range of concentrations of Hcy, and intracellular GPx activity was determined. Compared with control cells, cells treated with Hcy showed a significant reduction in GPx activity (up to 81% at 250 μm Hcy). In parallel with the decrease in GPx activity, steady-state GPx mRNA levels were also significantly decreased compared with control levels after exposure to Hcy, which appeared not to be a consequence of message destabilization. These data suggest a novel mechanism by which Hcy, in addition to increasing the generation of hydrogen peroxide, may selectively impair the endothelial cell’s ability to detoxify H2O2, thus rendering NO more susceptible to oxidative inactivation.

The care of patients with an abdominal aortic aneurysm: The Society for Vascular Surgery practice guidelines

The Clinical Practice Council of the Society for Vascular Surgery charged a writing committee with the task of updating practice guidelines, initally published in 2003, for surgeons and physicians who are involved in the preoperative, operative, and postoperative care of patients with abdominal aortic aneurysms (AAA). This document provides recommendations for evaluating the patient, including risk of aneurysm rupture and associated medical co-morbidities, guidelines for selecting surgical or endovascular intervention, intraoperative strategies, perioperative care, long-term follow-up, and treatment of late complications. Decision making related to the care of patients with AAA is complex. Aneurysms present with varying risks of

Surgical treatment of intact thoracoabdominal aortic aneurysms in the United States: Hospital and surgeon volume-related outcomes

OBJECTIVE Surgical treatment of intact thoracoabdominal aortic aneurysm (TAAA) is crucial to prevent rupture but is associated with high perioperative mortality. We tested the hypothesis that provider volume of surgical treatment of TAAA is an important determinant of operative outcome. Patients and methods Clinical information regarding repair of intact TAAA in 1542 patients from 1988 to 1998 was obtained from the Nationwide Inpatient Sample (NIS), a stratified discharge database of a representative 20% of US hospitals. Demographic data included age, sex, race, nature of admission, and comorbid conditions. Annual hospital volume of TAAA treated was grouped into terciles and defined as low (LVH; 1-3 cases [median, 1]), medium (MVH; 2-9 cases [median, 4]), or high (HVH; 5-31 cases [median, 12]). Annual surgeon volume was defined as low (LVS; 1-2 cases [median, 1]) or high (HVS; 3-18 cases [median, 7]). The primary outcome measure was in-hospital postoperative mortality. Secondary outcome measures included length of stay, and cardiac, pulmonary, and renal complications. Adjusted and unadjusted analyses were conducted. RESULTS Overall mortality was 22.3%. Mortality improved over time. LVH and HVH differed in mortality rates (27.4% vs 15.0%; P <.001). Mortality between LVS and HVS also differed significantly (25.6% vs 11.0%; P <.001). When controlling for patient demographic data, comorbid conditions, and postoperative complications, both hospital and surgeon volume were significant predictors of mortality for intact TAAA repair (LVS: odds ratio [OR] 2.6, P <.001; LVH: OR 2.2, P <.001; and MVH: OR 1.7, P =.004). CONCLUSIONS Greater hospital and surgeon TAAA treatment volumes contribute to better outcome. Given the relative high perioperative mortality associated with TAAA repair, regionalization of care to high-volume providers with consistently lower postoperative mortality deserves consideration by patients, physicians, and health care planners.

Role and Results of Surgery in Acute Type B Aortic Dissection Insights From the International Registry of Acute Aortic Dissection (IRAD)

Background— The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era. Methods and Results— A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean±SD age, 60.6±15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter >6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age >70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49). Conclusions— The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients.

Renal Artery Aneurysms: A 35-year Clinical Experience With 252 Aneurysms in 168 Patients

ObjectiveTo define the relevance of treating renal artery aneurysms (RAAs) surgically. Summary Background DataMost prior definitions of the clinical, pathologic, and management features of RAAs have evolved from anecdotal reports. Controversy surrounding this clinical entity continues. MethodsA retrospective review was undertaken of 168 patients (107 women, 61 men) with 252 RAAs encountered over 35 years at the University of Michigan Hospital. Aneurysms were solitary in 115 patients and multiple in 53 patients. Bilateral RAAs occurred in 32 patients. Associated diseases included hypertension (73%), renal artery fibrodysplasia (34%), systemic atherosclerosis (25%), and extrarenal aneurysms (6.5%). Most RAAs were saccular (79%) and noncalcified (63%). The main renal artery bifurcation was the most common site of aneurysms (60%). RAAs were often asymptomatic (55%), with a diagnosis made most often during arteriographic study for suspected renovascular hypertension (42%). ResultsSurgery was performed in 121 patients (average RAA size 1.5 cm), including 14 patients undergoing unilateral repair with contralateral RAA observation. The remaining 47 patients (average RAA size 1.3 cm) were not treated surgically. Operations included aneurysmectomy and angioplastic renal artery closure or segmental renal artery reimplantation, aneurysmectomy and renal artery bypass, and planned nephrectomy for unreconstructable renal arteries or advanced parenchymal disease. Eight patients underwent unplanned nephrectomy, being considered a technical failure of surgical therapy. Dialysis-dependent renal failure occurred in one patient. There were no perioperative deaths. Late follow-up (average 91 months) was available in 145 patients (86%). All but two arterial reconstructions remained clinically patent. Secondary renal artery procedures included percutaneous angioplasty, branch embolization, graft thrombectomy, and repeat bypass for late aneurysmal change of a vein conduit. Among 40 patients with clearly documented preoperative and postoperative blood pressure measurements, 60% had a significant decline in blood pressure after surgery while taking fewer antihypertensive medications. Late RAA rupture did not occur in the nonoperative patients, but no lessening of this group’s hypertension was noted. ConclusionSurgical therapy of RAAs in properly selected patients provides excellent long-term clinical outcomes and is often associated with decreased blood pressure.

Current concepts in the pathogenesis of abdominal aortic aneurysm

Abdominal aortic aneurysms (AAAs) are a significant medical problem with a high mortality. The primary diagnostic code for AAA accounts for approximately 150,000 inpatient hospital admissions per year. The most recent published data from the National Vital Statistics Report on Deaths from the year 2000 show that AAAs and aortic dissection composed the tenth leading cause of death in white men 65 to 74 years old and accounted for nearly 16,000 deaths overall. The year 2000 National Hospital Discharge Summary reports more than 30,000 open operations for repair of AAAs in the United States. Understanding the cause of AAAs therefore becomes an important undertaking. The pathogenesis of AAAs is complex and multifactorial. Histologically, AAAs are characterized by destruction of elastin and collagen in the media and adventitia, smooth muscle cell loss with thinning of the medial wall, infiltration of lymphocytes and macrophages, and neovascularization. Inflammation is a common underlying feature of both aneurysm disease and atherosclerosis. However, atherosclerosis is primarily found within the intima and media, whereas aneurysm disease typically affects the media and adventitia. A National Heart, Lung and Blood Institute Request for Applications (HL-99-007) entitled “Pathogenesis of Abdominal Aortic Aneurysms” identified four mechanisms relevant to AAA formation: proteolytic degradation of aortic wall connective tissue, inflammation and immune responses, biomechanical wall stress, and molecular genetics. PROTEOLYTIC DEGRADATION OF AORTIC WALL CONNECTIVE TISSUE

Surgeon volume as an indicator of outcomes after carotid endarterectomy: An effect independent of specialty practice and hospital volume

BACKGROUND High-volume hospitals have been shown to have superior outcomes after carotid endarterectomy (CEA), but the contribution of surgeon volume and specialty practice to CEA outcomes in a national sample is unknown. STUDY DESIGN Using the National Inpatient Sample for 1996 and 1997, 35,821 patients who underwent CEA (ICD-9-CM code 3812) and had data for unique surgeon identification were studied. Surgeons were categorized in terms of annual CEA volume as low-volume surgeons (< 10 procedures), medium-volume surgeons (10 to 29), and high-volume surgeons (> or = 30). Data from cardiac, general, neurologic, and vascular surgical practices were analyzed. In-hospital mortality, postoperative stroke, and prolonged length of stay (> 4 days) were the primary outcomes variables. Unadjusted and case-mix adjusted analyses were performed. RESULTS The overall in-hospital mortality was 0.61%. CEA was performed annually by high-volume surgeons in 52% of patients, by medium-volume surgeons in 30% of patients, and by low-volume surgeons in 18% of patients. Observed mortality by surgeon volume was 0.44% for high-volume surgeons, 0.63% for medium-volume surgeons, and 1.1% for low-volume surgeons (p < 0.001). The postoperative stroke rate was 1.14% for high-volume surgeons, 1.63% for medium-volume surgeons, and 2.03% for low-volume surgeons (p < 0.001). Surgeon specialty had no statistically significant effect on mortality or postoperative stroke. In the logistic regression model, increased risk of mortality was associated with emergent admission (odds ratio [OR] = 2.1; 95% confidence interval [CI] 1.6 to 2.8, p < 0.001), patient age > 65 years (OR = 2.0; 95% CI 1.3 to 3.1, p = 0.001), low-volume surgeon (OR = 1.9; 95% CI 1.4 to 2.5, p < 0.001), and COPD (OR = 1.8; 95% CI 1.3 to 2.5, p = 0.001). Low hospital CEA volume (< 100) was not a significant risk factor in the multivariate analysis. CONCLUSIONS More than 50% of the CEAs in the United States are performed by high-volume surgeons with superior outcomes. Health policy efforts should focus on reducing the number of low-volume surgeons, regardless of surgeon specialty or total hospital CEA volume.

Epidemiology of aortic aneurysm repair in the United States from 2000 to 2010

OBJECTIVE Broad application of endovascular aneurysm repair (EVAR) has led to a rapid decline in open aneurysm repair (OAR) and improved patient survival, albeit at a higher overall cost of care. The aim of this report is to evaluate national trends in the incidence of unruptured and ruptured abdominal aortic aneurysms (AAAs), their management by EVAR and OAR, and to compare overall patient characteristics and clinical outcomes between these two approaches. METHODS A retrospective analysis of the cross-sectional National Inpatient Sample (2000-2010) was used to evaluate patient characteristics and outcomes related to EVAR and OAR for unruptured and ruptured AAAs. Data were extrapolated to represent population-level statistics through the use of data from the U.S. Census Bureau. Comparisons between groups were made with the use of descriptive statistics. RESULTS There were 101,978 patients in the National Inpatient Sample affected by AAAs over the 11-year span of this study; the average age was 73 years, 21% were women, and 90% were white. Overall in-hospital mortality rate was 7%, with a median length of stay (LOS) of 5 days and median hospital charges of

Surgeon specialty and provider volumes are related to outcome of intact abdominal aortic aneurysm repair in the United States.

58,305. In-hospital mortality rate was 13 times greater for ruptured patients, with a median LOS of 9 days and median charges of

Neutrophil Depletion Inhibits Experimental Abdominal Aortic Aneurysm Formation

84,744. For both unruptured and ruptured patients, EVAR was associated with a lower in-hospital mortality rate (4% vs 1% for unruptured and 41% vs 27% for ruptured; P < .001 for each), shorter median LOS (7 vs 2; 9 vs 6; P < .001) but a 27%-36% increase in hospital charges. CONCLUSIONS The overall use of EVAR has risen sharply in the past 10 years (5.2% to 74% of the total number of AAA repairs) even though the total number of AAAs remains stable at 45,000 cases per year. In-hospital mortality rates for both ruptured and unruptured cases have fallen by more than 50% during this time period. Lower mortality rates and shorter LOS despite a 27%-36% higher cost of care continues to justify the use of EVAR over OAR. For patients with suitable anatomy, EVAR should be the preferred management of both ruptured and unruptured AAAs.