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.

Hypercholesterolemia superimposed by experimental hypertension induces differential distribution of collagen and elastin.

We studied the mural distribution of collagen types I and III and tropoelastin in enhanced experimental atherogenesis induced in rabbits by hyperlipidemia superimposed by hypertension. Animals were fed a high-cholesterol diet for 5 weeks and also subjected to midthoracic aortic coarctation for 4 weeks. Serum cholesterol levels were increased and blood pressure was elevated proximal to the coarctation. Foam cell lesions developed in the aorta proximal to the coarctation. In situ hybridization and immunohistochemistry showed that gene expression of collagen types I and III and tropoelastin was upregulated, with a differential distribution across the arterial wall. New collagen type I was mainly distributed in the intima, the outer media, and the adventitia. New collagen type III was spread more uniformly across the wall, including the adventitia, whereas tropoelastin was mainly localized in intimal foam cell lesions. Morphometric data showed an increase in wall thickness. These results suggest that collagen types I and III play a role in remodeling of the aortic wall in response to hypertension. The remarkable involvement of the adventitia in this response indicates that the adventitia is an important component of the arterial wall. Tropoelastin is closely associated with foam cell lesion formation, suggesting a role for this component in atherogenesis as well.

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.

Apolipoprotein (a) fragments in relation to human carotid plaque instability.

PURPOSE: An elevated plasma level of lipoprotein (a) is an independent risk factor for atherothrombotic cardiovascular disease by yet undefined mechanisms. We have previously reported that matrix metalloproteinases cleave apolipoprotein (a) into 2 main fragments, F1 and F2, the latter (the C-terminal domain) exhibiting in vitro a high-affinity binding to extracellular matrix components, including fibrin(ogen). We therefore tested the hypothesis that the lipoprotein (a) matrix metalloproteinase-derived F2 is localized in potentially or morphologically unstable human carotid plaque at regions of increased matrix metalloproteinase activity. METHODS: Carotid plaques removed after endarterectomy (n = 18) were evaluated for structural features indicative of instability (thin fibrous cap, inflammation, and proximity of the necrotic core to the lumen); each plaque was classified as unstable (n = 10) or stable (n = 8). Western blot analysis was performed to quantitate apolipoprotein (a) and its fragments F1 and F2 in plaque extracts. Immunohistochemical staining was used to localize apolipoprotein (a) and its fragments within the atherosclerotic plaque. In situ zymography was used to determine regions of gelatinase (matrix metalloproteinase 2 and matrix metalloproteinase 9) activity. RESULTS: Western blot analyses demonstrated a 2.5-fold higher density of F2 in unstable plaques than in stable plaques (3.07 +/- 1.9 vs 1.18 +/- 0.8; P <.05). In morphologically unstable plaques, there was preferential distribution of F2 within regions of fibrous cap inflammation and/or foam cell accumulation and within abluminal necrotic cores. In morphologically stable plaques, however, localization was predominantly found in the medial smooth muscle cells. Regions of enhanced matrix metalloproteinase 2 and matrix metalloproteinase 9 activity co-localized with the transmural distribution of F2 within the plaque. CONCLUSIONS: These findings suggest that F2 in regions of increased matrix metalloproteinase activity is a potential mechanism for superimposed thrombotic events in morphologically unstable human carotid plaques. The relationship between plasma lipoprotein (a) levels and accumulation of F2 and the potential correlation of F2 to human plaque disruption and thrombosis warrant further study.

Differential transmural distribution of gene expression for collagen types I and III proximal to aortic coarctation in the rabbit.

To assess the effects on the biosynthesis of collagen types I and III associated with an acute increase in blood pressure, we established a mid-thoracic aortic coarctation in the rabbit and studied gene expression and protein accumulation of these collagen types proximal to the stenosis 1, 3 and 7 days and 2, 4 and 8 weeks after coarctation. The mRNA level of type I collagen pro-alpha2(I) was maximal at 3 days and returned to normal at 4 weeks. mRNA of pro-alpha2(I) was localized mainly in the outer media, adventitia and intima. Accumulation of type I collagen and its precursors was increased by 3 days, peaked at 4 weeks, and decreased toward normal by 8 weeks, corresponding to the distribution of pro-alpha2(I) mRNA. Gene expression for pro-alpha1(III) was similar to that of pro-alpha2(I) but was distributed throughout the media. We conclude that the mechanical stresses associated with an acutely induced alteration in pressure initiate rapid gene expression for collagen types I and III in the aortic wall. The response for collagen type I, predominantly in the outer media and adventitia, suggests that these regions play an immediate role in the resistance to excessive dilatation of the aorta. The diffuse response for collagen type III in the media suggests participation in a more extensive remodeling response associated with the reinforcement and reorganization of the musculo-elastic fascicles.

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.

Increased flow and shear stress enhance in vivo transforming growth factor-beta1 after experimental arterial injury.

We have previously demonstrated that high-flow (HF) conditions inhibit experimental intimal hyperplasia. We hypothesized that such flow conditions may alter transforming growth factor-beta1 (TGF-beta1) after mural injury. The right common carotid artery (CCA) was balloon-injured in 54 New Zealand White male rabbits. Flow was thereafter preserved (normal flow [NF]), reduced by partial outflow occlusion (low flow [LF]), or increased by ligation of the left CCA (HF). Four sham-operated animals served as uninjured controls. Mean blood flow and pressure in the right CCA were measured before and after flow modulation and before euthanasia (3, 7, and 14 days). TGF-beta1 mRNA and protein levels in the right CCA were determined by Northern and ELISA analyses at each time point. At 7 and 14 days, intimal hyperplasia was quantified, and the transmural localization of TGF-beta1 was determined by immunohistochemical analysis. Mean flow was reduced from 22+/-1 to 10+/-3 mL/min in the LF group and increased to 34+/-2 mL/min in the HF group (P<0.001). Blood pressure was not different among the flow groups for all time points. Wall shear stress was markedly decreased in the LF group to 14+/-4 dyne/cm(2) and increased in the HF group to 63+/-6 dyne/cm(2) at 7 days compared with values in uninjured controls (39+/-2 dyne/cm(2), P<0.001) and the NF group (44+/-7 dyne/cm(2), P<0.001). At 14 days, wall shear stress was similar among the flow groups. The intima-to-media ratio was 5- and 2-fold greater in the LF group than in the HF and NF groups at 14 days. mRNA levels for TGF-beta1 and its active ligand were increased in the HF group by at least 2- and 3-fold, respectively, at 3 and 7 days compared with levels in uninjured controls and the LF group (P<0.05) but were not different among the flow groups at 14 days. TGF-beta1 preferentially localized in the abluminal vascular smooth muscle cells of the HF arterial segments. Flow- and shear-mediated release of TGF-beta1 may therefore play a role in abrogating the proliferative and migratory response of vascular smooth muscle cells in the early stages after mural injury.

Gene therapy enhances the antiproliferative effect of radiation in intimal hyperplasia.

BACKGROUND: Although ionizing radiation (IR) has been demonstrated to attenuate vessel wall restenosis and intimal hyperplasia (IH), dose-related mural injury and atrophy are possible deleterious side effects. We tested the hypothesis that a radiosensitizing strategy may improve IR-induced inhibition of in vivo vascular smooth muscle cells (VSMCs) without influencing apoptotic cell death. METHODS: In 28 New Zealand White rabbits, the right common carotid artery (CCA) was injured and subjected to low-flow conditions to promote IH. The CCA was transfected with an adenoviral vector incorporating the cytosine deaminase (CD) gene (1 x 10(9) PFU/ml). 5-Fluorocytosine (5-FC), a prodrug that is converted to the radiosensitizing agent 5-fluorouracil (5-FU) by CD, was thereafter administered intravenously. The CCA was exposed to 5 Gy IR at 24 h. Intimal/medial (I/M) area and thickness ratios were determined in the harvested CCAs at 14 days. VSMC proliferative and apoptotic indices were assessed with immunohistochemistry. RESULTS: A 50% reduction in I/M area was found in rabbits treated with IR and IR + CD/5-FC (0.19 +/- 0.03 and 0.18 +/- 0.02) when compared with untreated controls (UC) (0.37 +/- 0.06) (P = 0.005). This finding was substantiated by attenuation of I/M thickness in the IR groups [0.47 +/- 0.13 (IR), 0.41 +/- 0.11 (IR + CD/5-FC), 0.61 +/- 0.17 (UC)] (P = 0.007). The number of proliferating VSMCs was notably smaller when IR was combined with CD/5-FC (4.17 +/- 1.16 vs 2.97 +/- 1.09 log transformed cells/mm(2), P < 0.07). Apoptosis was similar in all groups. CONCLUSIONS: Both IR alone and IR combined with a radiosensitizing agent are effective in attenuating experimental IH. However, combination therapy is synergistic and achieves greater inhibition of VSMC proliferation and may involve selective killing of radioresistant S-phase VSMCs. IR + CD/5-FC represents a novel therapeutic strategy that offers potential for long-term control of IH.

Biomechanical factors as regulators of biological responses to vascular grafts.

Biomechanical forces have been implicated in the induction and progression of intimal hyperplastic thickening in vein, prosthetic, and endovascular bypass grafts. Graft implantation imposes significant alterations is shear and tensile forces. Such physical forces play an important role in modulating those cellular and molecular events that underlie regulation of vascular healing and adaptation. Characterization of such hemodynamic variables that induce perpetual medial vascular smooth muscle cell proliferation and migration will help in identification of those grafts at risk for occlusion and limited long-term patency and in design of therapeutic strategies that attenuate progressive intimal hyperplasia.

Irradiation for the treatment of intimal hyperplasia.

Intimal hyperplasia represents a serious complication limiting the long-term benefits of vascular interventions such as balloon angioplasty and stent placement. Although pharmacological interventions have attempted to curtail restenosis, they have not been shown to be effective to date. Radiotherapy is one alternative that has shown promise as an inhibitor of intimal hyperplasia in several animal models. Irradiation causes cell death by producing irreparable damage to DNA. This is believed to be the mechanism of inhibition of VSMC proliferation. Delivery of irradiation can be either intraluminal via an angiographically directed catheter or extraluminal using an external radiation source such as an x-ray device. Intraluminal irradiation has generally utilized either gamma or beta-emitting sources. Both have been effective in producing a dose response, although some studies advocate the use of beta-type irradiation as a safer, more efficient means of delivery. Extraluminal irradiation also has been an effective inhibitor of intimal hyperplasia. Studies suggest that this form of irradiation provides a more even-dose distribution to vessel walls than an intravascular delivery system. The use of radiotherapy has more recently been extended to clinical trials, and initial studies have shown promising results. The success of irradiation must be balanced with its potential complications including radiation-induced arteritis, coronary artery stenosis, and secondary development of malignancy. Although these have been associated with irradiation, the dose used in these cases was often considerably higher than those used in the treatment of intimal hyperplasia. Finally, with the advent of gene therapy, irradiation may provide an additional means of supplementing this new type of therapy through radiation-inducible gene therapy.

Flow regulation of 72-kD collagenase IV (MMP-2) after experimental arterial injury.

BACKGROUND: MMP-2 plays a key role in basement membrane degradation and in the migration of proliferating smooth muscle cells after vascular injury. Because low flow and shear stress have been related to the localization and progression of intimal hyperplasia, we hypothesized that flow conditions modulate in vivo MMP-2 transcription and activity in a model of injury-induced intimal thickening. METHODS AND RESULTS: The right common carotid artery (CCA) was balloon-injured in 21 New Zealand White male rabbits. Flow was thereafter preserved (normal flow, n=7), reduced by partial outflow occlusion (low flow, n=7), or increased by ligation of the left CCA (high flow, n=7). In 15 other animals (controls without injury), flow was reduced (n=5), increased (n=5), or preserved (n=5). Mean blood flow and pressure in the right CCA were measured before and after flow modulation (day 0) and before the rabbits were killed (day 7). Northern analysis, gelatin-gel zymography, and fluorometric assays were performed on day 7 to determine MMP-2 mRNA levels and activity in relation to flow and intimal thickening. Mean flow was reduced from 21+/-1 to 7+/-1 mL/min (P<0.05) by outflow occlusion and increased to 31+/-2 mL/min (P<0.05) by ligation of the contralateral CCA. Blood pressure was not different between the flow groups. Hemodynamic parameters were similar for days 0 and 7 after flow modulation. In the injured right CCA, there was a 186% increase in MMP-2 mRNA with normal flow (P<0.05), a 366% increase with low flow (P<0.005), and only a 38% increase with high flow (P>0.05) compared with the uninjured CCA with normal flow. In the uninjured CCA, MMP-2 mRNA levels were increased by only 39% and 26% in the low- and high-flow groups, respectively, compared with normal-flow controls. The zymographic signal and quantitative fluorescent activity of gelatinase were markedly increased in both injured and uninjured CCAs subjected to low flow. Intimal thickening was observed after 1 week only in CCA segments with low flow and injury. CONCLUSIONS: Hemodynamic forces such as low flow upregulate injury-induced MMP-2 mRNA and appear to be more important in regulating MMP-2 activity than injury alone. This may facilitate migration of the smooth muscle cells and subsequent development of intimal thickening.

Low flow enhances platelet activation after acute experimental arterial injury.

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and migration to the subintima or intimal hyperplasia (IH) occur after arterial injury and are thought to be induced by mitogenic factors released from activated platelets. Because low flow (LF) and shear have been attributed to the localization and progression of IH, we postulated that hemodynamic factors may regulate the degree of platelet activation, as measured by plasma thromboxane B2 (TXB2) and platelet-derived growth factor-AB (PDGF-AB) release at regions of experimental arterial injury. METHODS: The right common carotid artery (CCA) was subjected to balloon injury in 18 New Zealand White male rabbits. Flow in the injured CCA was reduced by out-flow ligation (LF group, n = 6) or increased by ligation of the left CCA (high flow [HF] group, n = 6). In six other animals, flow was preserved (normal flow [NF] group). Mean blood flow and pressure in the right CCA were measured thereafter at 10 and 30 minutes. Plasma TXB2 and PDGF-AB levels were determined with the enzyme-linked immunosorbent assay method in each animal with blood samples taken systematically before injury (baseline) and in the distal CCA at similar time points. RESULTS: At 10 minutes, mean blood flow was reduced from 20 +/- 2 ml/min in the NF group to 7 +/- 1 ml/min in the LF group animals (p < 0.01) and increased to 32 +/- 2 ml/min in the HF group animals (p < 0.05). Mean arterial blood pressure did not differ among the groups. Hemodynamic parameters were similar at 10 and 30 minutes. TXB2 levels were more than fourfold greater in the LF group than in the HF and NF groups at both time points (p < 0.05). In addition, there was a twofold increase in plasma PDGF-AB level at 10 minutes in the LF group compared with baseline levels (p < 0.05). CONCLUSION: Platelet activation at regions of acute vascular injury was determined to be flow dependent. Upregulated platelet activity in low flow conditions may be due to increased platelet exposure time to subendothelial collagen and is greatly attenuated if normal or increased flow is present.

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.