Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and claudication

Peripheral arterial disease (PAD) continues to grow in global prevalence and consumes an increasing amount of resources in the United States health care system. Overall rates of intervention for PAD have been rising steadily in recent years. Changing demographics, evolution of technologies, and an expanding database of outcomes studies are primary forces influencing clinical decision making in PAD. The management of PAD is multidisciplinary, involving primary care physicians and vascular specialists with varying expertise in diagnostic and treatment modalities. PAD represents a broad spectrum of disease from asymptomatic through severe limb ischemia. The Society for Vascular Surgery Lower Extremity Practice Guidelines committee reviewed the evidence supporting clinical care in the treatment of asymptomatic PAD and intermittent claudication (IC). The committee made specific practice recommendations using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system. There are limited Level I data available for many of the critical questions in the field, demonstrating the urgent need for comparative effectiveness research in PAD. Emphasis is placed on risk factor modification, medical therapies, and broader use of exercise programs to improve cardiovascular health and functional performance. Screening for PAD appears of unproven benefit at present. Revascularization for IC is an appropriate therapy for selected patients with disabling symptoms, after a careful risk-benefit analysis. Treatment should be individualized based on comorbid conditions, degree of functional impairment, and anatomic factors. Invasive treatments for IC should provide predictable functional improvements with reasonable durability. A minimum threshold of a >50% likelihood of sustained efficacy for at least 2 years is suggested as a benchmark. Anatomic patency (freedom from restenosis) is considered a prerequisite for sustained efficacy of revascularization in IC. Endovascular approaches are favored for most candidates with aortoiliac disease and for selected patients with femoropopliteal disease in whom anatomic durability is expected to meet this minimum threshold. Conversely, caution is warranted in the use of interventions for IC in anatomic settings where durability is limited (extensive calcification, small-caliber arteries, diffuse infrainguinal disease, poor runoff). Surgical bypass may be a preferred strategy in good-risk patients with these disease patterns or in those with prior endovascular failures. Common femoral artery disease should be treated surgically, and saphenous vein is the preferred conduit for infrainguinal bypass grafting. Patients who undergo invasive treatments for IC should be monitored regularly in a surveillance program to record subjective improvements, assess risk factors, optimize compliance with cardioprotective medications, and monitor hemodynamic and patency status.(AU)

Long-term results justify autogenous infrainguinal bypass grafting in patients with end-stage renal failure.

INTRODUCTION: Infrainguinal bypass grafting for limb-threatening ischemia in patients with end-stage renal disease is generally thought to be associated with increased operative risk and poor long-term outcome. This retrospective study was undertaken to examine the modern-era, long-term results of infrainguinal bypass grafting in dialysis-dependent patients. METHODS: Over the past 5 years in a single institution, 425 lower extremities (368 consecutive patients) were revascularized for the indication of limb salvage. Sixty-four patients (82 limbs) were dialysis-dependent at the time of revascularization, and this group was analyzed separately. They exhibited statistically significant higher incidences of diabetes (83% vs 56%; P <.001), hypertension (91% vs 74%; P <.001), and more distal vascular disease, which required a greater proportion of proximal anastomoses at the popliteal level (24% vs 11%; P <.01) and distal anastomoses at the infrapopliteal level (75% vs 65%; P <.05). RESULTS: Despite the higher prevalence of comorbid conditions and distal disease in patients with renal failure, their perioperative 30-day mortality rate remained low (4.9%) and was not significantly different from that in patients with functioning kidneys (2.9%; P = not significant). After a median follow-up of 11 months (range, 0-60 months), the 3-year autogenous conduit secondary graft patency in patients with renal failure was no different than in patients with functioning kidneys (67% +/- 9% vs 64% +/- 5%; P = not significant). Nonautogenous conduits in dialysis-dependent patients exhibited a significantly poorer outcome with only 27% +/- 12% remaining secondarily patent at 2 years. As expected, both limb salvage and patient survival were significantly less in patients with renal faiture, although both exceeded 50% at 3 years (limb salvage 59% +/- 8% vs 68% +/- 5%; P <.05; patient survival 60% +/- 8% vs 86% +/- 4%; P <.001). The often-quoted phenomenon of limb loss, despite a patent bypass graft, occurred infrequently in this study (n = 3 of 82 limbs). CONCLUSION: Infrainguinal revascularization can be performed in dialysis-dependent patients with acceptable perioperative and long-term results, especially in patients in whom adequate autologous conduit is available.

Patency and limb salvage after infrainguinal bypass with severely compromised ("blind") outflow.

HYPOTHESIS: Infrainguinal graft patency and limb salvage are adversely affected by severely compromised outflow. DESIGN: Retrospective review of all infrainguinal bypass procedures performed at a single institution during a 5-year period. SETTING: University teaching hospital. PATIENTS: Two hundred seventy-four patients underwent infrainguinal bypass for limb salvage (351 grafts in 307 limbs). INTERVENTIONS: All infrainguinal bypasses originated from a femoral artery. The distal anastomosis in 279 grafts was located in an artery with at least 1 patent outflow vessel with anatomically normal end-artery runoff (Society for Vascular Surgery/International Society for Cardiovascular Surgery ad hoc committee runoff score, 1-9). The distal anastomosis of 72 grafts was located in an artery with only collateral outflow ("blind bypass"; runoff score, 10). MAIN OUTCOME MEASURES: Perioperative morbidity and mortality, primary-assisted and secondary graft patency, limb salvage, and survival. RESULTS: All data are presented as mean +/- SEM. Patients undergoing blind bypass were older (age, 70 +/- 2 vs. 66 +/- 1 years; P <.05) and had a higher incidence of hypertension (90% vs 70%; P <.05) and end-stage renal disease (24% vs. 13%; P <.05). Comparing patients undergoing blind bypass to bypass with at least 1 patent outflow vessel, there were no differences in the use of nonautogenous conduits (50% vs 59%; P =.21) or postoperative warfarin (30% vs 32%; P =.69), or in perioperative mortality rates (2.7% vs 3.2%; P =.79). After a median follow-up of 13 months (range, 0-60 months), 2-year secondary graft patency for the entire group was 63% +/- 4%. The secondary patency rate of blind bypass grafts was no different from that of grafts with at least 1 patent outflow vessel (67% +/- 7% vs. 64% +/- 4%; P was not significant). However, the 2-year limb salvage rate in limbs with blind outflow was significantly worse than in limbs with at least 1 patent outflow vessel (67% +/- 7% vs. 76% +/- 3%; P =.04). CONCLUSION: Acceptable long-term patency rates can be achieved in infrainguinal bypass grafts with blind outflow, although blind outflow remains a marker for subsequent limb loss in the chronically ischemic leg.

Angioplasty does not affect subsequent operative renal artery revascularization.

BACKGROUND: Although increased application of percutaneous renal artery angioplasty and stenting has facilitated nonoperative renal revascularization, patient outcomes after failed angioplasty are not established. METHODS: Renal artery revascularization was performed in 31 patients (38 arteries) from 1993 to 1999. Twenty patients underwent primary surgical repair, and 11 patients underwent secondary reconstruction after angioplasty (n = 7) or angioplasty and stenting (n = 4). Before operation, all patients had severe hypertension (blood pressure 166+/-5.2/92 +/- 2.7 mm Hg) that required an average of 3.0 +/- 0.2 medications for control. In addition, 12 patients (primary 45% vs secondary 27%; P = NS) had evidence of renal insufficiency (creatinine > or =1.7 mg/dL). RESULTS: There was no difference between primary and secondary procedures in the length of hospital stay (12+/- 1.4 vs. 12+/-3.2 days; P = NS), major morbidity (10% vs. 18%; P = NS) or perioperative mortality (overall mortality 2 of 31; primary 5% vs secondary 9%; P = NS). The majority of patients demonstrated improvement or cure of hypertension (primary 94% vs secondary 90%; P = NS) and stable or decreased creatinine (primary 74% vs secondary 82%; P = not significant). Overall survival (mean follow-up 22+/-3.5 months) was 89%+/-5.7%. CONCLUSIONS: Although this surgical series does not address the true outcomes of renal artery angioplasty, the results suggest that renal artery angioplasty does not prejudice subsequent surgical outcomes in patients who are carefully followed after angioplasty.

Estimating the contemporary in-hospital costs of carotid endarterectomy.

Carotid endarterectomy (CEA) is the treatment of choice for symptomatic carotid stenosis and selective asymptomatic lesions. Alternative approaches have recently been championed under the guise of increased efficacy and decreased cost. The purpose of this study was to determine the results and in-hospital costs of CEA in a university hospital in the modern era. A retrospective chart review was undertaken for all patients undergoing CEA between January 1995 and December 1997. This corresponded to the implementation of a clinical path and extended efforts toward cost reduction. Patients undergoing combined CEA and cardiopulmonary bypass were excluded (n = 3). Cost was analyzed by the hospital Office of Program Planning using TSI (Transition Systems, Inc.) software. Direct costs are related to the utilization of clinical resources and are therefore manageable by clinicians (bed, room, supplies, nursing staff, OR staff, radiology, pharmacy, etc.). Total costs additionally include administration and overhead costs not directly chargeable to patient accounts. The results of this study showed that CEA can be safely performed with brief hospital stays and reasonable hospital costs. Results of alternative interventions for the treatment of carotid stenosis should be compared to these contemporary data.

Effective hemodynamic diameter: an intrinsic property of vein grafts with predictive value for patency.

INTRODUCTION: Conduit size and quality are major determinants of the long-term success of infrainguinal autologous vein grafting. However, accurate measurement of the internal diameter of vein grafts is difficult given their variable wall thickness and taper. The purpose of this study was to define the "effective" internal diameter of a vein graft according to its hemodynamic properties and to determine its significance for graft patency. METHODS: Sixty infrainguinal bypass grafts performed on 57 patients were evaluated intraoperatively. Proximal and distal graft pressure and blood flow (Q(meas)) were measured with fluid-filled catheter transduction and ultrasonic transit-time flowimetry, respectively, after unclamping. Waveforms were recorded digitally at 200 Hz under baseline conditions and after stimulation with 60 mg of papaverine. According to Fourier transformation of the measured pressure gradient (DeltaP), the Womersley solution for fluid flow in a straight rigid tube was used to calculate theoretical flow waveforms (Q(calc)) for a range of graft diameters. The theoretical waveforms were then compared with the measured flow waveforms and the best-fit diameter chosen as the "effective hemodynamic diameter" (EHD). Only grafts in which the correlation coefficient of Q(calc) versus Q(meas) was more than 0.90 were accepted (n = 47) to assure validity of the hemodynamic model. After a mean follow-up of 12.5 months (range, 0.1-43.9 months), patency was determined by the life table method. Hemodynamic and clinical variables were tabulated, and their effect on patency determined the use of univariate and multivariate Cox regression. RESULTS: Mean EHD was 4.1 +/- 0.1 mm with a range of 2.5 to 5.7 mm. Administration of papaverine caused profound changes in DeltaP (+78% +/- 17%) and Q(meas) (+71% +/- 12%) as expected, but had no effect on EHD (+0.05% +/- 0.1%). Univariate regression identified five variables associated with decreased secondary patency (P <.10): low EHD, conduit source other than the greater saphenous vein, high baseline DeltaP(mean), female sex, and redo operation. Of these, only low EHD was significant after multivariate analysis (P =.03). Patency of small diameter grafts (EHD < 3.6 mm; n = 11) was compared with patency of larger grafts (EHD > 3.6 mm; n = 36) to test a frequently espoused clinical guideline. Grafts with an EHD less than 3.6 mm exhibited significantly lower secondary patency compared with larger grafts (P =.0001). The positive and negative predictive values for an EHD less than 3.6 mm for secondary graft failure for grafts with at least 1 year follow-up were 86% and 88%, respectively. CONCLUSION: An EHD is a unique parameter that quantifies conduit size and has a significant impact on vein graft patency. An EHD less than 3.6 mm portends graft failure.

Abdominal aortic aneurysm with aorta-left renal vein fistula with left varicocele.

Abdominal aortic aneurysm with spontaneous aorto-left renal vein fistula is a rare but well-described clinical entity usually with abdominal pain, hematuria, and a nonfunctioning left kidney. This report describes a 44-year-old man with left-sided groin pain and varicocele who was treated with conservative measures only. The diagnosis was eventually made when he returned with microscopic hematuria, elevated serum creatinine level, and nonfunction of the left kidney; computed tomography scan demonstrated a 6-cm abdominal aortic aneurysm, a retroaortic left renal vein, and an enlargement of the left kidney. This patient represents the youngest to be reported with aorto-left renal vein fistula and the second case with a left-sided varicocele.

Therapeutic plasma exchange for the acute management of the catastrophic antiphospholipid syndrome: beta(2)-glycoprotein I antibodies as a marker of response to therapy.

We describe two patients with the catastrophic antiphospholipid syndrome associated with elevation of beta(2)-glycoprotein I antibodies and fulminant thrombotic diatheses. Both patients were treated with therapeutic plasma exchange (TPE), which resulted in a marked decrease in antibody titer accompanied by an improved clinical outcome in one patient (IgG antibody). In the second patient, the outcome was poor despite TPE (IgA antibody). There were no significant complications of TPE in either case. Because of the fulminant nature of the catastrophic antiphospholipid syndrome, we conclude that a trial of TPE is warranted for the acute management. Further studies are needed to clarify which patients may benefit from this treatment.

Improving perioperative management of carotid endarterectomy.

Multiple components of the perioperative course of patients who undergo carotid endarterectomy must be tightly controlled in order to maintain an acceptably low complication rate. These factors include appropriate patient selection, routine assessment of cardiac risk factors, precise control of blood pressure intraoperatively and postoperatively, meticulous surgical technique and reliable monitoring for intraoperative cerebral ischemia. This discussion focuses on the vascular practice patterns at the University of Chicago and emphasizes intraoperative management and the safe utilization of intraluminal shunts.

Assessing outcomes, costs, and benefits of emerging technology for minimally invasive saphenous vein in situ distal arterial bypasses.

BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion has recently been approved for use. Despite the attractiveness of this approach (2 short incisions), benefits such as lower morbidity and shorter hospitalizations remain undocumented. To justify wide acceptance, minimally invasive surgical techniques must match conventional procedures in durability and cost while enhancing patient comfort. Often such comparisons are difficult during the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes of the MIAB procedures with a concurrent group of patients undergoing conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING: University medical center. PATIENT: The first 20 consecutive MIAB procedures in 19 patients performed between August 1, 1995, and July 31, 1997, were compared with 19 contemporaneous consecutive conventional in situ bypass procedures performed at the same institution. MAIN OUTCOME MEASURES: Operative time, postoperative length of stay, hospital costs, complications, primary assisted and secondary patency, limb salvage, and survival. RESULTS: The patient groups were comparable with respect to age, sex, incidence of smoking, coronary artery disease, hypertension, diabetes, renal failure, cerebrovascular disease, indication, and distal anastomosis level. The median operative time was significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and intraoperative completion arteriography more frequently showed retained arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median postoperative length of stay and total cost were 6.5 days and $18,000 for the MIAB group and 8 days and $27,800 for the conventional group (P > or = .05). There were no significant differences in major complications (10% in the MIAB group vs 11% in the conventional group), wound complications (10% vs 11%, respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%, respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively), limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing the MIAB procedure avoided lengthy vein exposure incisions without sacrificing short-term results. There was a trend toward decreased hospital stay and cost, which may be further realized as the clinical experience broadens. Although longer follow-up and larger cohorts will always be required to define durability, immediate access to outcomes and costs on small numbers of patients facilitates the early assessment of emerging technology.

Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis.

PURPOSE: The structural features that underlie carotid plaque disruption and symptoms are largely unknown. We have previously shown that the chemical composition and structural complexity of critical carotid stenoses are related to plaque size regardless of symptoms. To further determine whether the spatial distribution of individual plaque components in relation to the lumen corresponds to symptomatic outcome, we evaluated 99 carotid endarterectomy plaques. METHODS: Indications for operation were symptomatic disease in 59 instances (including hemispheric transient ischemic attack in 29, stroke in 19, and amaurosis fugax in 11) and angiographic asymptomatic stenosis > 75% in 40. Plaques removed after remote symptoms beyond 6 months were excluded. Histologic sections from the most stenotic region of the plaque were examined using computer-assisted morphometric analysis. The percent area of plaque cross-section occupied by necrotic lipid core with or without associated plaque hematoma, by calcification, as well as the distance from the lumen or fibrous cap of each of these features, were determined. The presence of foam cells, macrophages, and inflammatory cell collections within, on, or just beneath the fibrous cap was taken as an additional indication of plaque neoformation. RESULTS: The mean percent angiographic stenosis was 82% +/- 11% and 79% +/- 13% for the asymptomatic and symptomatic groups, respectively (p > 0.05). The necrotic core was twice as close to the lumen in symptomatic plaques when compared with asymptomatic plaques (0.27 +/- 0.3 mm vs 0.5 +/- 0.5 mm; p < 0.01). The percent area of necrotic core or calcification was similar for both groups (22% vs 26% and 7% vs 6%, respectively). There was no significant relationship to symptom production of either the distance of calcification from the lumen or of the percent area occupied by the lipid necrotic core or calcification. The number of macrophages infiltrating the region of the fibrous cap was three times greater in the symptomatic plaques compared with the asymptomatic plaques (1114 +/- 1104 vs 385 +/- 622, respectively, p < 0.009). Regions of fibrous cap disruption or ulceration were more commonly observed in the symptomatic plaques than in the asymptomatic plaques (32% vs 20%). None of the demographic or clinical atherosclerosis risk factors distinguished between symptomatic and asymptomatic plaques. CONCLUSIONS: These findings indicate that proximity of plaque necrotic core to the lumen and cellular indicators of plaque neoformation or inflammatory reaction about the fibrous cap are associated with clinical ischemic events. The morphologic complexity of carotid stenoses does not appear to determine symptomatic outcome but rather the topography of individual plaque components in relation to the fibrous cap and the lumen. Imaging techniques that precisely resolve the position of the necrotic core and evidence of inflammatory reactions within carotid plaques should help identify high-risk stenoses before disruption and symptomatic carotid disease.

Current results of surgical therapy for chronic mesenteric ischemia.

BACKGROUND: Although recognition of chronic mesenteric ischemia has increased in recent years, this disorder has continued to present diagnostic and therapeutic challenges. OBJECTIVE: To examine the modern results of surgical revascularization for chronic mesenteric ischemia. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: The management of 24 consecutive patients (mean +/- SEM age, 58 +/- 3 years; 5 men, 19 women) who were undergoing surgical treatment of chronic mesenteric ischemia between 1986 and 1996 was reviewed. INTERVENTION: Surgical mesenteric revascularization. MAIN OUTCOME MEASURES: Postoperative course, long-term graft patency rate, and long-term symptom-free survival rate. RESULTS: The most frequent presenting symptoms were postprandial abdominal pain (18 patients [75%]) and weight loss (14 patients [58%]). Less specific complaints included nausea and vomiting (8 patients [33%]), diarrhea (7 patients [29%]), and constipation (4 patients [17%]). Atherosclerotic risk factors were common, including tobacco use (20 patients [83%]), coronary artery disease (10 patients [42%]), and hypertension (10 patients [42%]). The cause was identified as atherosclerosis in 21 patients, median arcuate ligament compression in 2 patients who were monozygotic twins, and Takayasu arteritis in 1 patient. Lesions were localized to all 3 major visceral vessels (celiac artery, superior mesenteric artery [SMA], and inferior mesenteric artery) in 8 patients, celiac artery and SMA in 13, SMA alone in 2, and SMA and inferior mesenteric artery in 1. Seventeen patients underwent antegrade reconstructions from the supraceliac aorta to the SMA and/or celiac artery; 7 patients underwent revascularization by use of a retrograde bypass that originated from the infrarenal aorta or a prosthetic graft. There were no perioperative deaths although 1 patient died in the hospital 6 weeks after early graft failure and sepsis (overall in-hospital mortality, 4%). Follow-up ranged from 3 months to 10 years (median, 2.4 years). The mean +/- SEM 5-year primary graft patency rate, as objectively documented by use of contrast angiography or duplex scanning in 19 of 24 patients, was 78% +/- 11%. Primary failure was documented in 3 patients (at 3 weeks, 5 months, and 7 months). Two patients required a thrombectomy; 1 of these patients subsequently died of an intestinal infarction. The mean +/- SEM 5-year survival rate by use of life-table analysis was 71% +/- 11%. No patient with a patent graft experienced a symptomatic recurrence. CONCLUSIONS: Chronic mesenteric ischemia is usually a manifestation of advanced systemic atherosclerosis. Symptoms almost always reflect midgut ischemia in the distribution of the SMA. An antegrade bypass from the supraceliac aorta can be performed with acceptable operative morbidity and is currently the preferred reconstructive technique. Surgical revascularization affords long-term symptom-free survival in a majority of patients with chronic mesenteric ischemia.

Validation of a new and specific intraoperative measurement of vein graft resistance.

PURPOSE: Clinical studies have revealed that the most important predictor of successful bypass grafting is the origin and quality of the bypass conduit. Attempts at intraoperative evaluation of the hemodynamic properties of the conduit, including assessment of blood flow (Q), pressure gradients (delta P), and resistance (R), have not been useful. This is because each of these parameters measures the characteristics of the graft plus the outflow bed. To date, no specific measurement of the resistive properties of the conduit only is available. The purpose of this investigation was to evaluate longitudinal impedance (ZL) as a measure of conduit-specific resistance and to evaluate its potential in predicting the outcome of infrainguinal vascular reconstructions. METHODS: ZL was measured during surgery in 73 infrainguinal autologous vein reconstructions performed in 68 patients in two separate institutions over a 21-month period. Vein graft ultrasonic transit time Q and delta P (from proximal to distal anastomosis) were measured at baseline and after maximal peripheral vasodilatation with an intraarterial injection of papaverine 30 mg. Waveforms were recorded for 10 seconds at 200 Hz using a digital acquisition system. R was calculated as proximal mean pressure divided by mean blood flow (Q). After Fourier transformation, ZL was calculated as delta P/Q at each harmonic and total ZL (integral of ZL) was defined as the integral of moduli from 0 to 4 Hz. RESULTS: All hemodynamic variables were significantly affected by papaverine vasodilatation (delta P, 3.9 +/- 0.5 vs 6.3 +/- 0.8 mm Hg; Q, 78.2 +/- 7.0 vs 126 +/- 11 ml/min; R, 134 +/- 17 vs 72.7 +/- 6.2 x 10(3) dyne.sec.cm-5; p < 0.0001), except integral of ZL, which remained constant (31.1 +/- 2.8 vs 30.8 +/- 2.8 x 10(3) dyne.cm-5; p = NS). After follow-up of 1 week to 17 months (median, 5 months), the 1-year primary, primary-assisted, and secondary patency rates were 72% +/- 7%, 77% +/- 6%, and 81% +/- 6%, respectively. Using Cox analysis, primary patency was significantly associated with decreased integral of ZL (p = 0.0001), but not with baseline or papaverine-stimulated delta P, Q, delta P/Q, or R integral of ZL > 47 x 10(3) dyne.cm-5 predicted primary failure with 90% positive and negative predictive value. CONCLUSIONS: Intraoperative measurement of integral of ZL in infrainguinal vein grafts is independent of outflow conditions (that is, does not change with papaverine), and hence describes the resistive properties of the conduit only. In addition, these preliminary data suggest that integral of ZL is predictive of short-term primary patency. integral of ZL is the first available hemodynamic measurement that is conduit-specific and may therefore be a better predictor of graft patency than currently available methods.

Acute mesenteric ischemia.

The morbidity and mortality of acute mesenteric ischemia have remained high over the past 30 years despite heightened sensitivity to the diagnosis. Because the duration of the ischemic episode is the most significant determinant of outcome, an aggressive diagnostic and treatment protocol must be maintained. Although this stance may precipitate a number of negative angiographic studies, such an approach is the only opportunity for salvage in these critically ill patients.

Connexin43 gene expression in the rabbit arterial wall: effects of hypercholesterolemia, balloon injury and their combination.

The specialized functions of endothelium require intercellular communication between endothelial cells within the monolayer, and between endothelium and other cells present in the vessel wall. This is accomplished by a combination of paracrine soluble mediators and direct gap-junctional intercellular communication (GJIC) mediated by a family of connexin proteins. A prominent connexin expressed by vascular cells in vivo and in vitro is connexin 43 (Cx43). We have investigated the in vivo gene regulation of Cx43 in the context of vascular pathology, as a result of mechanical injury, hypercholesterolemia or both. The aortoiliac bifurcation in the rabbit was examined following three types of insult: (1) diet-induced hypercholesterolemia resulting in macrophage-rich fatty streak lesions, (2) mechanical, stretch-denudation injury resulting in intimal smooth muscle cell (SMC) proliferation and (3) mechanical injury superimposed on hypercholesterolemia resulting in a complex vascular lesion having characteristics of both interventions. The normal rabbit iliac artery expressed approximately equal levels of Cx43 mRNA in the medial SMC layers and in the endothelium. In hypercholesterolemia-induced atherosclerosis, Cx43 expression was most prominent in macrophage foam cells even though normocholesterolemic precursor monocytes did not express Cx43 mRNA. Antibodies directed specifically to Cx43 protein confirmed the expression of macrophage gap junction protein in these cells. Medial SMC in hypercholesterolemia exhibited less Cx43 than their normal counterparts in control animals. Mechanical injury in the absence of hypercholesterolemia resulted in intimal thickening in which Cx43 expression in the intimal SMC was equivalent to that in the subjacent medial SMC, both being approximately equivalent to normal uninjured rabbit medial SMC expression. Cell-specific expression of Cx43 in combined mechanical injury/hypercholesterolemia was similar to that observed in hypercholesterolemia alone: Cx43 upregulation in macrophages, while medial SMC were downregulated. Normo- and hypercholesterolemic alveolar macrophages of the lung and Kupffer cells of the liver did not exhibit induction of Cx43 mRNA, nor did macrophages isolated from peritoneal or bronchial lavage fluid of the same animals. This work extends our previous finding of Cx43 upregulation in human atherectomy tissue and demonstrates that atherosclerotic lesions in situ, in a controlled animal model of atherosclerosis, exhibit cell-specific changes in Cx43 gene expression. Changes in medial SMC migration, proliferation and phenotype, as well as enhanced interactions between adherent/infiltrating monocytes and endothelium may be related to modified GJIC pathways in the vessel wall.

Mechanisms of neurologic deficits and mortality with carotid endarterectomy.

OBJECTIVE: To evaluate the incidence and etiology of perioperative complications of carotid endarterectomy. DESIGN: Retrospective review of carotid endarterectomies performed over 13 years. Risk factors, indications, results of electroencephalographic (EEG) monitoring, and outcomes were evaluated. SETTING: University medical center. PATIENTS: Three hundred sixty-seven consecutive primary carotid endarterectomies were performed on 336 patients. Indications for operation included transient ischemic attack (48.5%), asymptomatic stenosis (24%), stroke (17%), nonlateralizing ischemia (9.5%), and stroke-in-evolution (1%). MAIN OUTCOME MEASURES: Postoperative neurologic deficits (permanent and transient) and deaths were correlated with preoperative symptoms, probable mechanism of the neurologic event, intraoperative EEG changes, and the use of intraoperative shunts. RESULTS: Four new permanent neurologic deficits (1.1%) and one transient postoperative deficit were noted. Of the five deficits, three were related to undiagnosed intraoperative cerebral ischemia and two were related to perioperative emboli. Three perioperative deaths (0.8%) occurred: two of myocardial infarction and one of an intracerebral hemorrhage from a ruptured arteriovenous malformation. Intraoperative EEG tracings for the most recent consecutive 175 procedures were analyzed. Shunts were used in 45 patients (26%), 38 of whom demonstrated significant EEG changes with carotid clamping. CONCLUSIONS: Carotid endarterectomy can be performed with a low risk of stroke (1.1%) and death (0.8%). Stroke was due to cerebral ischemia or embolization. With meticulous surgical technique, death is due to myocardial ischemia and not neurologic events.