Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

Reducing aneurysm sac growth and secondary interventions following endovascular abdominal aortic aneurysm repair by preemptive coil embolization of the inferior mesenteric artery and lumbar arteries.

OBJECTIVE: Type II endoleak (EL-2) is the most common complication following endovascular aneurysm repair (EVAR), leading to continued sac growth and potential rupture. In this study, we examined the association between patency of the inferior mesenteric artery (IMA) and lumbar arteries (LAs) with respect to sac growth. The effect of preemptive embolization of the IMA and/or LAs on the need for secondary interventions for sac growth post-EVAR was also evaluated. METHODS: A retrospective cohort study was performed on consecutive patients who underwent EVAR for non-ruptured, infrarenal abdominal aortic aneurysms (AAAs) from January 2012 to December 2020. A select group of patients underwent preemptive embolization of the IMA and/or LA. Patients with any types I, III, or IV endoleaks were excluded. Patency of the IMA and LA on preoperative computed tomography angiogram (CTA) was evaluated on TeraRecon workstation. All secondary interventions to treat EL-2 were recorded. Sac growth was defined as centerline axial diameter increase of ≥5 mm on follow-up CTA. RESULTS: A total of 300 patients (mean age, 74 ± 8.5 years; 83.7% male) underwent EVAR. Ninety-nine patients had preemptive embolization of the IMA and/or LA. Mean follow-up of the cohort was 59.3 ± 30.5 months. Thirty-six patients (12%) demonstrated sac growth on follow-up; 12 of these (33.3%) had preemptive embolization. The median time until detection of sac growth was 28.8 months (interquartile range, 15.2-46.5 months), with a mean growth of 10.1 ± 6.4 mm. Sac growth was significantly associated with presence of EL-2: 27 of 36 (75%) with EL-2 vs 9 of 36 (25%) without EL-2 (P < .001). Patients with sac growth had a higher mean total number (2.6 ± 1.5) of patent lower LAs (L3, L4) compared with those without (2.0 ± 1.4; P = .03). Patency of L1, L2, and L3 LAs were not associated with sac growth. However, patency of at least one L4 LA was significantly associated with sac growth (14.8% vs 7.7%; P = .04). The highest incidence of sac growth (17.6%) was seen when both IMA and L4 LA were patent; significantly different from the lowest incidence (5.3%) when both were occluded preoperatively (P = .018). Preemptive coiling of the IMA and/or LA significantly reduced the need for post-EVAR secondary intervention for sac growth. Freedom from post-EVAR secondary intervention was achieved in 92 of 99 (92.9%) pre-EVAR coiled patients vs 163 of 201 (81.5%) patients who did not undergo pre-EVAR coiling (P = .009). CONCLUSIONS: Preemptive coil embolization of the IMA and LAs, especially L4 LA, reduces the need for secondary interventions for sac growth, potentially improving the long-term durability of EVAR.

The role of the inferior mesenteric artery in predicting secondary intervention for type II endoleak following endovascular aneurysm repair.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is associated with a greater risk of graft-related complications and need for secondary interventions compared with open repair. Type II endoleak (EL-2) is the most common complication. We examined the hypothesis that a functionally occluded inferior mesenteric artery (IMA) before EVAR was associated with fewer secondary interventions for EL-2. METHODS: All nonruptured abdominal aortic aneurysms (AAA) treated by EVAR using U.S. Food and Drug Administration-approved endografts from January 2005 to December 2017 were retrospectively reviewed, including computed tomography angiograms. Preoperative patency of the IMA and any secondary interventions performed after the index EVAR procedure were recorded. A functionally occluded IMA was defined as one that was (1) chronically occluded or severely stenosed on preoperative imaging or (2) coil embolized before EVAR. Secondary interventions for persistent EL-2 were indicated when AAA sac diameter increased by more than 5 mm. RESULTS: The study cohort comprised 490 patients (84 women) with a mean age of 74.8 ± 8.2 years. The mean preoperative AAA diameter was 5.6 ± 0.9 cm. One hundred twenty-nine patients (26.3%) died during follow-up. The mean follow-up of survivors was 38 months. Types (prevalence) of endoleak were I (2.4%), II (18.9%), III (0.7%), IV (0.5%), and V (0.2%). Patients with a functionally occluded IMA underwent significantly fewer secondary interventions for EL-2 compared with patients with a patent IMA (2.6% vs 7.1%; P = .020). All secondary interventions in the functionally occluded IMA group involved the lumbar arteries (LA). When the IMA was patent, secondary interventions were equally distributed between the LA and IMA. Logistic regression confirmed that a functionally patent IMA was associated with a greater number of secondary interventions for EL-2 (odds ratio, 3.0; 95% confidence interval, 1.2-7.5; P = .025). CONCLUSIONS: Patients with a functionally occluded IMA required significantly fewer secondary interventions for EL-2 after EVAR. In addition, the type of vessels intervened on were primarily LA. Among patients with a patent IMA, preoperative coil embolization may decrease secondary interventions and improve the long-term durability of EVAR.

Role of type II endoleak in sac regression after endovascular repair of infrarenal abdominal aortic aneurysms.

OBJECTIVE: Endovascular repair (EVAR) of infrarenal aortic aneurysms (AAA) is increasingly used in patients with suitable aortic morphology conforming to device-specific instructions for use. Despite improvements in graft design, type II endoleak (EL-2) from the inferior mesenteric artery (EL-IMA) or the lumbar artery (EL-LA) remains the Achilles' heel of EVAR. The objective of this study was to evaluate the natural history of the AAA sac after EVAR. We hypothesized that persistent EL-2 would be associated with inferior AAA sac volume regression. METHODS: A retrospective analysis was performed on all nonruptured AAA treated by elective EVAR using Food and Drug Administration-approved endografts from January 2005 to December 2008 in our facility. Review of medical records and preoperative and follow-up computed tomography angiograms at 1, 6, and 12 months was performed. Patients with type I, III, and IV endoleaks were excluded, as were those lost to all follow-up. AAA size and volume were analyzed using TeraRecon software (Aquarius Intuition, Foster City, Calif). Change in AAA sac volume was compared in patients with and without EL-2, and with an occluded vs patent IMA. RESULTS: The study cohort comprised 191 patients (161 men, 30 women) with a mean age of 74 years. The mean preoperative AAA diameter was 5.5 cm (range, 4-11 cm), and mean volume was 137.45 cm(3). EL-2 was present in 24% at completion of EVAR and in 9% at a mean follow-up of 6 months (range 4-8 months). Completion angiography at 1 month showed 63% of EL-2 had resolved. Those with EL-2 present at 1 month had statistically inferior sac regression compared with those who did not (23% reduction vs 2% increase at 1 year; P = .002). Preoperatively, the IMA was occluded by coils or was chronically occluded in 82 patients vs 109 patients who had a patent IMA. At the 6-month follow-up, patients with an occluded IMA had an EL-2 rate of 2.4% vs 14.7% in those with a patent IMA (P = .005 by t-test). Sac volume regression was 21.8% in those with an occluded IMA vs 13.2% in those with a patent IMA (P = .004 by t-test). Regression in AAA sac volume was highly significant in patients with occluded IMA, at 30% vs 16% at 1 year (P = .0018 by two-sided t-test). CONCLUSIONS: The presence of persistent EL-2 after EVAR results in inferior AAA sac regression. A preoperatively patent IMA is associated with increased rates of EL-2 and inferior AAA sac regression. Consideration should be given to preoperative occlusion of a patent IMA before EVAR.

Coil embolization of an acutely expanding spontaneous splenic artery dissection.

Symptomatic dilation of a spontaneous splenic artery dissection is a very rare and potentially catastrophic nonatherosclerotic vascular disease. Splenic artery rupture has not been reported after acute diffuse dilation, but it has been reported with celiac artery dissections. We believe treatment is mandatory if pain persists despite blood pressure control. The presentation and endovascular treatment of a spontaneous celiac trunk dissection with continued expansion of the splenic artery branch are discussed.

Safety of autologous drainage blood reinfusion following total knee arthroplasty prepared with hydrogen peroxide.

In a clinical in vivo study, wound blood collected from an autologous reinfusion drain of patients undergoing elective total knee arthroplasty was examined to investigate if hydrogen peroxide bone surface preparation had an adverse effect on blood destined to be reinfused. The post-operative drain blood of thirty-eight patients was collected after pre-implantation bone preparation being performed either with or without the use of hydrogen peroxide. Filtered drain blood samples were analyzed and mean results for treatment / control groups respectfully were: haemoglobin (g/L) 98.6/100.9, p=0.7221; haemoglobin change from baseline (g/L) -39.1/-32.9, p=0.2117; MCV (fL) 94.6/93.1, p=0.2897; MCV change from baseline (fL) 2.0/2.5, p=0.6417; potassium (mmol/L) 4.5/4.6, p=0.8212; free haemoglobin (g/L) 1.2/1.3, p=0.4387; methaemoglobin (%) 0.2/0.2, p=0.8112; presence of echinocytes (%) 14/18, p=1.0000. These were all within safe limits for reinfusion. Under the study conditions, application of hydrogen peroxide followed by thorough lavage of the knee joint did not appear to result in any untoward degradation of the extravasated blood that might preclude its use for postoperative autologous drainage blood reinfusion.

Evaluation of thrombolysis using tissue plasminogen activator in lower extremity deep venous thrombosis with concomitant femoral-popliteal venous segment involvement.

OBJECTIVE: Current guidelines recommend thrombolytic therapy for iliofemoral deep venous thrombosis (DVT). Anticoagulation is the standard treatment for femoral-popliteal and tibial-level DVT. The objective of this study was to evaluate the efficacy of catheter-directed thrombolysis (CDT) using tissue plasminogen activator vs standard anticoagulation alone in patients with lower extremity DVT involving the femoral-popliteal segment. METHODS: A retrospective review was performed of patients referred to the vascular surgery service with lower extremity DVT from 2006 to 2015. Patients who had DVT involving the femoral-popliteal segment were identified, including some patients who had concomitant involvement of iliofemoral and tibial veins. Patients with pure iliofemoral and tibial vein DVT were excluded from this analysis. Review of medical records, follow-up ultrasound studies, hypercoagulable panel, and venography were performed. Comparison of outcomes between patients who received thrombolytic therapy using tissue plasminogen activator and patients who received standard anticoagulation alone was performed. The primary outcomes measured were restoration of patency of the femoral-popliteal segment at 3 months, incidence of post-thrombotic syndrome (PTS), and valvular dysfunction. Secondary outcomes were incidence of bleeding, in-hospital mortality, and pulmonary embolism. RESULTS: The study cohort was composed of 191 patients (CDT, n = 89; anticoagulation alone, n = 102) who met inclusion criteria. Most patients with thrombus involving the femoral-popliteal segment also had proximal venous segment involvement, with 93% of the patient cohort having proximal iliofemoral DVT. Patients who did not receive CDT were older (mean age of 64 years vs 51 years; P < .001) and had more associated comorbidities, such as diabetes, immobility, and cancer. A significant number of patients who received CDT had a positive family history for DVT (21.3% vs 8.8%; P = .023), and it was more likely to be their first episode of DVT (73.0% vs 55.9%; P = .016). Patients who received CDT were more likely to have restoration of patency (74.7% vs 11.1%; P < .001) and lower incidence of PTS (21.3% vs 73.4%; P < .001) and valvular dysfunction (23.0% vs 66.7%; P < .001) compared with patients who were treated with anticoagulation alone. Incidence of bleeding was significantly more for patients treated with anticoagulation alone (14.7% vs 5.6%; P = .018) compared with patients who received CDT. On multivariate analysis, age was the predominant risk factor for bleeding. There was no significant difference in mortality and pulmonary embolism. CONCLUSIONS: In patients with acute proximal DVT and concomitant femoral-popliteal venous segment involvement, CDT resulted in superior patency at 3 months and less PTS and valvular reflux. This was achieved without increase in bleeding complications compared with anticoagulation alone. Age was the major factor predictive of bleeding in either group. The results of this study may not be applicable to patients with pure femoral-popliteal venous segment DVT because only 3% of patients had this finding.

Mycotic aneurysm of the superior mesenteric artery: a delayed complication from a neglected septic embolus-a case report.

Mycotic aneurysm formation in a visceral artery carries a significant risk of mortality and morbidity. The authors present a case of a symptomatic superior mesenteric artery aneurysm secondary to a septic embolus in a patient who had undergone aortic valve replacement. The patient initially presented with evidence of acute intestinal ischemia from a presumed embolic source. Although an extensive bowel resection was performed, an adequate search for the embolus was not carried out. Prompt diagnosis and removal of suspected septic emboli must be performed to avoid the formation of delayed mycotic aneurysms.

Splenic rupture from metastatic granulosa cell tumor 29 years after curative resection: case report and review of the literature.

Granulosa cell tumors account for 2 to 3 per cent of all ovarian neoplasms. This case report describes a patient with splenic rupture from a bulky metastatic deposit 29 years after her initial surgery. A review of the literature regarding the patterns and timing of recurrence is also discussed.

Transaortic endarterectomy for primary mesenteric revascularization.

The optimal approach to revascularization for chronic mesenteric ischemia has not been firmly established during the past three decades. The present study was undertaken to evaluate the safety and results of primary mesenteric revascularization for chronic mesenteric ischemia by transaortic endarterectomy. A descriptive retrospective analysis of 14 patients who underwent trap-door transaortic endarterectomy for primary mesenteric revascularization was performed. Clinical presentations of the patients included abdominal pain (n=13) and weight loss (n=7). All patients underwent preoperative aortography and subsequent elective reconstruction. Demographic features, perioperative, and long-term outcomes were analyzed. The study population consisted of 12 females and two males with a mean age of 67 years. The mean operative duration was 3 hours with an ischemic time of 33 minutes. The initial success rate of mesenteric revascularization was 93%. One early graft failure was salvaged with urgent embolectomy without bowel resection. There was no hospital mortality, but the overall postoperative morbidity rate was 50% (n=7). Thirteen patients (93%) were discharged within 2 weeks. Late recurrent ischemia and intestinal infarction developed in one patient, requiring emergency bowel resection. Sustained relief of symptoms was achieved in 13 of 14 patients (93%). The overall survival rates were 85% +/-10.0% and 77% +/-11.7% at 1 and 3 years, respectively. Transaortic endarterectomy is a safe and effective technique for elective primary mesenteric revascularization for patients with chronic mesenteric ischemia. This approach allows simultaneous revascularization of multiple visceral arteries and achieves durable relief of symptoms.

Renal venous diversion: an unusual treatment for renal vein thrombosis.

Renal venous thrombosis most commonly occurs in the setting of nephrotic syndrome, hypercoagulability, or dehydration. This can usually be treated with systemic anticoagulation, and the diversion is via natural draining tributaries, eg, adrenal, lumbar, or gonadal veins. Occasionally, renal venous thrombosis results from extension of a thrombotic process, such as a large renal cell carcinoma with tumor thrombus extension into the infrahepatic inferior vena cava resulting in thrombosis of the inferior vena cava and contralateral renal vein. Herein, we report a case of left renal vein thrombosis relieved by diversion through the inferior mesenteric vein.

Comparative analysis of autogenous infrainguinal bypass grafts in African Americans and Caucasians: the association of race with graft function and limb salvage.

OBJECTIVE: African Americans (AAs) are at risk for developing diabetes mellitus and atherosclerosis. Whether race influences the results of infrainguinal arterial reconstruction is unclear. The purpose of this study was to compare the results of autogenous infrainguinal bypasses in AAs and Caucasians to determine the association of race with graft function and limb salvage. METHODS: This was a retrospective, comparative cohort study of AA and Caucasian patients who had undergone autogenous infrainguinal bypass surgery. Only single-limb bypasses in each patient cohort were considered in this analysis. In patients who had undergone bilateral lower limb bypasses, the first limb bypass was chosen as the index bypass procedure. RESULTS: From January 1985 to December 2003, 1459 autogenous infrainguinal bypasses were performed in 1459 patients for lower limb ischemia. Within this group, 89 AA patients/vein grafts formed the study cohort. The control group comprised 1370 Caucasian patients/vein grafts. Compared with the Caucasian cohort, AA patients were significantly younger (median age, 65 vs 70 years, respectively; P = .001) and predominantly female (57% vs 41%, respectively; P = .002). AA patients also had a higher prevalence of diabetes mellitus, hypertension, cerebrovascular disease, congestive heart failure, and dialysis-dependent renal failure. More AA than Caucasian patients presented with gangrene (34% vs 16%, respectively; P = .001), and more underwent bypass surgery for limb salvage indications (91% vs 81%, respectively; P = .01). The venous conduit used was predominantly the greater saphenous vein (AA, 83%; Caucasian, 85%), and the site of distal anastomosis was at the tibial/pedal level in 67% of AA and 61% of Caucasian patients. Overall morbidity (AA, 28%; Caucasian, 23%) and 30-day mortality (AA, 3%; Caucasian, 3%) were similar. Thirty-day graft failure was significantly greater in AAs than Caucasians (12% vs 5%, respectively; P = .003). The overall 5-year primary graft patency (+/-SE) was significantly worse in AA patients (AA, 52% +/- 6%; Caucasian, 67% +/- 2%; P = .009). The 5-year limb salvage rate (+/-SE) was also significantly worse in AA patients (AA, 81% +/- 5%; Caucasian, 90% +/- 1%; P = .04). With the Cox proportional hazard model, significant risk factors associated with primary graft failure were AA race, age younger than 65 years, female sex, secondary reconstructions, tibial bypasses, and critical limb ischemia. Significant risk factors associated with limb loss were age younger than 65 years, female sex, absence of coronary disease, presence of critical limb ischemia, and secondary reconstructions. CONCLUSIONS: Autogenous infrainguinal bypass surgery in AAs is associated with poorer primary graft patency and limb salvage rates compared with those of Caucasians. This may partially account for the higher rate of limb loss in AA patients with peripheral arterial occlusive disease.

Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common disease with as yet unclear cause. Increased matrix metalloproteinase (MMP) levels in the plasma and aorta are a consistent finding in AAA. Although the role of MMPs in AAA has largely been attributed to degradation of the extracellular matrix proteins, the effects of MMPs on the mechanisms of aortic contraction are unclear. The purpose of this study was to test the hypothesis that MMPs promote aortic dilation by inhibiting the Ca2+ mobilization mechanisms of smooth muscle contraction. METHODS: Isometric contraction and 45Ca2+ influx were measured in aortic strips isolated from male Sprague-Dawley rats treated or not treated with MMP-2 and MMP-9. RESULTS: In normal Krebs solution (2.5 mmol/L Ca2+ ) phenylephrine (10-5 mol/L) caused contraction of the aortic strips, which was significantly inhibited (P < .05) by MMP-2 (maximum, 48.9% +/- 5.0%) and to a greater extent by MMP-9 (maximum, 69.8% +/- 6.2%). The MMP-induced inhibition of phenylephrine contraction depended on concentration and time. The inhibitory effects of MMPs on phenylephrine contraction were reversible. In Ca2+ -free (2 mmol/L ethylene glycol bis[beta-aminoethyl ether]-N,N,N',N'-tetraacetic acid) Krebs solution phenylephrine caused a small contraction that was not inhibited by MMP-2 or MMP-9, which suggests that MMPs do not inhibit Ca2+ release from the intracellular stores. Membrane depolarization with 96 mmol/L of potassium chloride, which stimulates Ca2+ entry from the extracellular space, caused a time-dependent and reversible contraction, which was inhibited by MMP-2 and MMP-9. Histologic studies of MMP-treated tissues stained with hematoxylin-eosin or Verhoeff stain for elastin confirmed the absence of degradation of the extracellular matrix. MMP-2 and MMP-9 also caused significant inhibition of 45Ca2+ influx induced by phenylephrine and potassium chloride. CONCLUSIONS: These data suggest that MMP-2 and MMP-9 promote aortic dilation by inhibiting the Ca2+ entry mechanism of vascular smooth muscle contraction. CLINICAL RELEVANCE: Abdominal aortic aneurysm (AAA) is a slow and progressive disease. The late stages of AAA are characterized by degenerative changes in the extracellular matrix and smooth muscle components of the aortic wall. The present study describes novel inhibitory effects of matrix metalloproteinase (MMP) on the Ca2+ entry mechanisms of aortic smooth muscle contraction, even in the absence of extracellular matrix degradation. The MMP-induced inhibition of aortic contraction may further explain the role of increased MMP activity particularly during the early development of AAA. Chronic exposure to MMPs may lead to protracted inhibition of aortic contraction, progressive aortic dilation, and aneurysm formation. MMP-9 is a more potent inhibitor of aortic contraction than MMP-2, consistent with a more dominant role in AAA. Restoration and preservation of smooth muscle contractile function by specific inhibitors of MMPs may represent a new strategy in preventing the progression of small AAA.

Elastase promotes aortic dilation by inhibiting Ca2+ influx into vascular smooth muscle.

Abdominal aortic aneurysm (AAA) is a common vascular disease with, as of yet, unclear mechanism. Increased elastase activity and elastin degradation in the aorta are consistent findings in human AAA. Also, elastase perfusion of the aorta promotes aortic dilation in animal models of AAA. Although elastase-induced degradation of extracellular matrix proteins and the ensuing inflammation of the aortic wall have been implicated as possible causes of the aortic dilation in AAA, little is known regarding the effects of elastase on the mechanisms of aortic smooth muscle contraction. The purpose of this study was to test the hypothesis that elastase promotes aortic dilation by inhibiting the Ca2+ mobilization mechanisms of smooth muscle contraction. Isometric contraction and 45Ca2+ influx were measured in aortic strips isolated from male Sprague-Dawley rats non-treated or treated with elastase. Initial experiments suggested that elastase alone caused matrix degradation. To avoid potential degradation of the extracellular matrix proteins by elastase, the same experiments were repeated in the presence of saturating concentrations of elastin (10 mg/ml). In normal Krebs (2.5 mM Ca2+), phenylephrine (Phe, 10(-5) M) caused contraction of the aortic strips that was significantly inhibited by elastase. The elastase-induced inhibition of Phe contraction was concentration- and time-dependent. At 5 U/ml elastase, the inhibition of Phe contraction was rapid in onset (2.4 +/- 0.3 minutes) and complete in 32 +/- 4 minutes. The inhibitory effects of elastase on Phe contraction were partially reversible. In Ca2+-free (2 mM EGTA) Krebs, Phe caused a small contraction that was not inhibited by elastase, suggesting that elastase does not inhibit Ca2+ release from the intracellular stores. Membrane depolarization by 96 mM KCl, which stimulates Ca2+ entry from the extracellular space, caused a contraction that was inhibited by elastase in a time-dependent and reversible fashion. The reversible inhibitory effects of elastase, particularly in the presence of saturating concentrations of elastin, suggest that they are not due to dissolution of the extracellular matrix or permanent damage to the smooth muscle contractile proteins. Elastase also caused significant inhibition of Phe- and KCl-induced 45Ca2+ influx. These data suggest that elastase promotes aortic relaxation by inhibiting the Ca2+ entry mechanism of vascular smooth muscle contraction, and thus further explain the role of increased elastase activity during the early development of AAA.

The role of a putative microfibrillar protein (80 kDa) in abdominal aortic aneurysm disease.

BACKGROUND: We previously have reported the partial amino acid sequence of a putative aortic autoantigen in patients with abdominal aortic aneurysm (AAA) disease that has homologies with an elastin-associated microfibrillar protein found in aorta of pigs. This study was conducted to further define the role that microfibrillar proteins may play as autoantigens in AAA disease. MATERIALS AND METHODS: An extraction procedure was performed on AAA tissue using high concentrations of guanidinium hydrochloride (GuHCl) under reducing conditions. The microfibrillar extract was then probed with immunoglobulin (Ig) G isolated with Protein A from phosphate-buffered saline (PBS) extracts of 10 AAA specimens and 6 atherosclerotic, nonaneurysmal aortas. Immunoblotting was also performed with serum IgG from 9 AAA patients and 9 normal control patients. Immunohistochemistry using goat anti-human IgG (Fc-specific) on AAA tissue and AAA wall IgG on normal aorta were also performed. RESULTS: Eight of 10 AAA wall IgG reacted with an 80-kDa protein from the aortic microfibrillar extract, compared to 0 out of 6 atherosclerotic wall IgG (P = 0.0035, Fischer's Exact Test). Staining of the 80-kDa band appeared to increase with progressive additions of GuHCl, up to extract SKGCGC. Immunoblotting using serum IgG from 9 AAA patients and 9 normal control patients on the aneurysm microfibrillar extracts revealed no reactive bands. Immunohistochemistry using IgG from AAA wall showed the localization of the antibodies to the adventitial connective tissue matrix, mainly collagen fibers. CONCLUSIONS: These observations suggest that a collagen-associated protein, extractable by a microfibrillar extraction procedure from aortic aneurysm tissue, may be among the targets of an autoimmune response in AAA disease.

Elastase-induced suppression of endothelin-mediated Ca2+ entry mechanisms of vascular contraction.

Abdominal aortic aneurysm (AAA) is associated with increased endothelin (ET-1), both systemically and locally in the aorta. Also, elastase activity is increased in human AAA, and elastase perfusion of the aorta induces aneurysm formation in animal models of AAA. However, whether elastase directly affects the ET-1-induced mechanisms of aortic smooth muscle contraction is unclear. Isometric contraction and 45Ca2+ influx were measured in aortic strips isolated from male Sprague-Dawley rats and treated with elastase (5 U/mL). To avoid degradation of the extracellular matrix proteins by elastase, experiments were performed in the presence of elastin (10 mg/mL). In normal Krebs solution (2.5 mmol/L Ca2+), ET-1 (10(-7) mol/L) caused contraction of aortic strips that was inhibited by elastase (5 U/mL). The elastase-induced inhibition of ET-1 contraction was slow in onset (4.6+/-0.4 minutes), time-dependent, complete in 34+/-3 minutes, and reversible. In Ca2+-free Krebs solution, caffeine (25 mmol/L) caused a small contraction that was not inhibited by elastase, suggesting that elastase does not inhibit Ca2+ release from the intracellular stores. Membrane depolarization by 96 mmol/L KCl, which stimulates Ca2+ entry from the extracellular space, caused a contraction that was inhibited by elastase in a concentration-dependent, time-dependent, and reversible fashion. The reversible inhibitory effects of elastase, particularly in the presence of elastin, suggest that they are not due to dissolution of the extracellular matrix or smooth muscle contractile proteins. Elastase also inhibited ET-1 and KCl-induced 45Ca2+ influx. Thus, elastase directly inhibits ET-1-induced Ca2+ entry mechanisms of vascular smooth muscle contraction, which may explain the role of elastase and ET-1 during the development of AAA.

Infrainguinal vein bypass graft revision: factors affecting long-term outcome.

OBJECTIVES: We sought to determine the long-term results of revision procedures performed for repair of stenotic lesions in infrainguinal vein bypass grafts. METHODS: A retrospective review of 188 vein grafts, from a total series of 1260 bypasses, undergoing revision of stenotic lesions between January 1, 1987, and December 31, 2002, at Brigham & Women's Hospital was undertaken. Lesions were identified by recurrence of symptoms, change in examination findings, or with routine duplex ultrasound graft surveillance. Demographic and medical risk factors, and surgical variables were analyzed with respect to patency outcomes after the initial graft revision, with descriptive statistics, logistic regression, and life table analysis. Primary and secondary patency rates were determined from the time of graft revision. RESULTS: Patients included 108 men (57%) and 80 women (42%) who underwent revision at a mean age of 67.8 years. One hundred thirty grafts required only a single revision, whereas 58 required subsequent additional revisions. Revision procedures included 99 vein patches (52.7%), 23 jump grafts (12.2%), 23 interposition grafts (12.2%), 8 transpositions to new outflow vessels (4.3%), and 35 balloon angioplasty procedures (18.6%). During a mean follow-up of 1535 days, 5-year primary patency rate was 49.3% +/- 4.5% (SE) and 5-year secondary patency rate was 80.3% +/- 3.6%. There was no difference in patency rate for different revision procedures, type of vein graft, indication for the original procedure, or for patients with diabetes mellitus or renal disease. The overall limb salvage rate was 83.2% +/- 3.5% 5 years after graft revision. With COX proportional hazard analysis of time to failure of the revision procedure, the outflow level of the original bypass and the time of revision proved to be an important predictor of durability of the graft revision. Revision of popliteal bypass grafts resulted in a 60% 5-year primary patency rate, whereas revision of tibial grafts resulted in a 42% 5-year primary patency rate (P = .004; hazard ratio [HR], 2.06). Five-year secondary patency rates were 90% and 76%, respectively (P = .009; HR = 3.43). The timing of the graft revision proved an additional predictor. Grafts revised within 6 months of the index operation had lower primary patency than those with later revisions (42.9% vs 80.7%, respectively; HR = 1.754; P = .0152). CONCLUSIONS: Vein graft revisions offer durable patency and limb salvage rates after repair of stenotic infrainguinal bypass grafts. Vigilant ongoing surveillance is essential, because 30.9% of revised grafts will develop additional lesions that will require repair. Tibial level bypass grafts that require early repeat intervention to treat graft stenosis are at particular risk for development of subsequent lesions.

Bypass in the absence of ipsilateral greater saphenous vein: safety and superiority of the contralateral greater saphenous vein.

PURPOSE: The purposes of this study were to evaluate the long-term results of different autogenous conduits used for infrainguinal bypass when ipsilateral greater saphenous vein (IGSV) is absent or inadequate and to determine the impact on the contralateral lower extremity. METHODS: The study was performed as a retrospective evaluation of a prospective vascular registry together with review of patient records and telephone follow-up. RESULTS: From January 1990 to June 2000, 226 autogenous infrainguinal reconstructions were performed in 203 patients without adequate IGSV. The patients consisted of 128 men and 98 women, with a mean age of 69 years. Prevalent risk factors included diabetes (51%) and prior coronary bypass (46%). Limb salvage was the predominant indication (93%), and 59% of the procedures were secondary reconstructions. All bypasses were completed with autogenous vein, which included contralateral greater saphenous vein (CGSV; 31%), single-segment lesser saphenous vein (5%), single-segment arm vein (19%), and autogenous composite vein (45%). Bypasses were performed to the tibial and pedal arteries in 84% of the cases. The 30-day mortality and graft occlusion rates were 1% and 9%, respectively. The overall postoperative morbidity rate was 24%, with a 7% rate of major complications. Follow-up was complete in 95% of patients over a mean period of 24 months (range, 0.1 to 106 months). The 5-year primary patency rates were significantly better for CGSV compared with autogenous composite vein grafts (61% +/- 7% versus 39% +/- 6%; P <.009). The 5-year secondary patency (60% to 73%) and limb salvage (78% to 81%) rates did not differ significantly between the three groups. Follow-up of the contralateral lower limb revealed that nine of 226 limbs (4%) were amputated at a mean of 36 months after the ipsilateral bypass. The overall 5-year contralateral limb preservation rate was 90% +/- 3%. Contralateral vein harvest and the presence of diabetes did not affect the need for bypass or amputation of the contralateral limb. CONCLUSION: For most patients with inadequate IGSV, the CGSV is the alternative conduit of choice because of its length, superior performance, ease of harvest, and minimal risk to the donor limb.

Outcome in patients at high risk after open surgical repair of abdominal aortic aneurysm.

OBJECTIVE: Outcomes after surgical repair of abdominal aortic aneurysm (AAA) in patients at high risk remain poorly defined. We investigated the short-term and long-term results of open repair of infrarenal AAA in a high-risk and comparison low-risk patient population. METHODS: Conventional open surgical repair of nonruptured infrarenal AAA was performed in 572 consecutive patients from 1990 to 2000. Patients were considered at high risk if they had one or more of the following criteria: age 80 years or more, creatinine level 3.0 mg/dL or higher, severe pulmonary insufficiency, severe cardiac dysfunction, or hepatic failure. A retrospective review was carried out to determine relative risks, perioperative morbidity and mortality, and long-term survival. A P value of less than.05 was considered statistically significant. RESULTS: One hundred twenty-eight of the study patients (22%) were at high risk and 444 were at low risk. Patients at high risk were older (77 versus 69 years; P <.001), were more likely female (26% versus 16%; P <.009), and had larger (mean, 5.9 versus 5.6 cm; P <.024), more symptomatic (20% versus 13%; P <.001) aneurysms. The 30-day operative mortality rate for the high-risk group was 4.7%, compared with 0.0% (P <.001) in the low-risk group. Overall and major morbidity rates were 29% and 14% in the high-risk cohort versus 17% (P <.003) and 5% in the low-risk cohort, respectively. The 5-year survival rate was 46% (standard deviation, 5.2%) in the high-risk group versus 74% (standard deviation, 2.6%) in the low-risk group (P <.001). On multivariate analysis, age 80 years or more (P <.046), creatinine level 3.0 mg/dL or higher (P <.022), prior stroke (P <.012), and pulmonary dysfunction were significant predictors of poor operative outcome (30-day mortality and major morbidity), and female gender (P <.035), cardiac dysfunction (P <.004), creatinine level 3.0 mg/dL or higher (P <.0001), prior stroke (P <.005), and pulmonary dysfunction (P <.0001) negatively impacted long-term survival rates. CONCLUSION: This study shows that open repair of infrarenal AAA in patients at high risk can be performed with relative safety and with results that offer a benchmark with which endovascular repair can be compared. Poor long-term survival in this population, however, highlights the importance of patient selection and raises the question of whether repair of many patients at high risk is warranted.

Initial experience with minimally invasive in situ bypass procedure with blind valvulotomy.

OBJECTIVE: The in situ vein (ISV) bypass is uniquely suited to technical modifications designed to reduce the wound morbidity of infrainguinal revascularization. A technique of "blind" valvulotomy and selective vein branch ligation was used, and a preliminary study was performed to assess safety and efficacy. METHODS: From November 1998 to July 2001, all patients for infrainguinal bypass procedures underwent evaluation for inclusion in the study. Thirty-five patients underwent ISV bypass procedures with an expandable, self-centering valvulotome (ESV). Intraoperative selection of veins suitable for the study was assisted with venography and duplex scanning. The ISV bypass procedures were performed with initial groin and distal incisions, with smaller incisions to ligate significant arteriovenous fistulae (AVF). Duplex graft scanning was performed at routine intervals after surgery. RESULTS: Thirty-seven ISV grafts were performed from the common femoral artery to the popliteal (n = 14), tibial (n = 20), and dorsalis pedis (n = 3) arteries. In 35 cases (95%), a full-length incision was avoided. With ESV, all valves in 34 cases (92%) were effectively lysed. Proximal extension of the distal incision was performed in four cases (10.8%). The mean number of incisions per case was 3.1 +/- 1.7. One graft failed within 30 days (2.7%), with successful revision. During the early follow-up period (9.9 +/- 7.3 months; range, 1 to 33 months), 44% of residual AVF closed spontaneously (15 of 34 AVF; 16 patients) and two anastomotic stenoses and two symptomatic AVF were corrected surgically. Four late graft occlusions occurred, with a 1-year cumulative primary patency rate of 77% and a secondary patency rate of 92%. CONCLUSION: Blind valvulotomy with ESV facilitates safe and effective minimally invasive ISV bypass. Resultant graft patency rates appear comparable with results with open techniques. This preliminary experience warrants further study to refine patient selection criteria and operative technique and to better clarify the natural history of residual AVF.