Cystathionine γ Lyase Sulfhydrates the RNA Binding Protein Human Antigen R to Preserve Endothelial Cell Function and Delay Atherogenesis.

BACKGROUND: Hydrogen sulfide (H2S), generated by cystathionine γ lyase (CSE), is an important endogenous regulator of vascular function. The aim of the present study was to investigate the control and consequences of CSE activity in endothelial cells under physiological and proatherogenic conditions. METHODS: Endothelial cell CSE knockout mice were generated, and lung endothelial cells were studied in vitro (gene expression, protein sulfhydration, and monocyte adhesion). Mice were crossed onto the apolipoprotein E-deficient background, and atherogenesis (partial carotid artery ligation) was monitored over 21 days. CSE expression, H2S bioavailability, and amino acid profiling were also performed with human material. RESULTS: The endothelial cell-specific deletion of CSE selectively increased the expression of CD62E and elevated monocyte adherence in the absence of an inflammatory stimulus. Mechanistically, CD62E mRNA was more stable in endothelial cells from CSE-deficient mice, an effect attributed to the attenuated sulfhydration and dimerization of the RNA-binding protein human antigen R. CSE expression was upregulated in mice after partial carotid artery ligation and in atheromas from human subjects. Despite the increase in CSE protein, circulating and intraplaque H2S levels were reduced, a phenomenon that could be attributed to the serine phosphorylation (on Ser377) and inhibition of the enzyme, most likely resulting from increased interleukin-1ß. Consistent with the loss of H2S, human antigen R sulfhydration was attenuated in atherosclerosis and resulted in the stabilization of human antigen R-target mRNAs, for example, CD62E and cathepsin S, both of which are linked to endothelial cell activation and atherosclerosis. The deletion of CSE from endothelial cells was associated with the accelerated development of endothelial dysfunction and atherosclerosis, effects that were reversed on treatment with a polysulfide donor. Finally, in mice and humans, plasma levels of the CSE substrate l-cystathionine negatively correlated with vascular reactivity and H2S levels, indicating its potential use as a biomarker for vascular disease. CONCLUSIONS: The constitutive S-sulfhydration of human antigen R (on Cys13) by CSE-derived H2S prevents its homodimerization and activity, which attenuates the expression of target proteins such as CD62E and cathepsin S. However, as a consequence of vascular inflammation, the beneficial actions of CSE-derived H2S are lost owing to the phosphorylation and inhibition of the enzyme.

Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta.

Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-ß1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-ß1 as an attractive target for manipulation in this context.

Proximal Aortic Neck Progression: Before and After Abdominal Aortic Aneurysm Treatment.

Several risk factors including short or highly angulated proximal aortic neck have been associated with long-term outcomes after endovascular or open abdominal aortic aneurysm (AAA) repair. However, research data have emerged recently concerning the behavior of proximal aortic neck, and several authors have tried to evaluate this behavior after endovascular or open repair. Additionally, computed tomography angiography (CTA) remains the golden standard for detecting and observing the morphology of an AAA, both before and after treatment. Moreover, the question of whether the proximal neck's progression independently affects postoperative morbidity and reintervention risks still remains. Therefore, this focused review aims to present all relevant data on the behavior of an AAAs neck, based on CTA imaging before and after repair, in order to produce useful conclusions for future clinical practice.

Morphologic changes and outcome following endovascular abdominal aortic aneurysm repair as a function of aneurysm size.

HYPOTHESIS: Small infrarenal abdominal aortic aneurysms have a more favorable clinical and morphologic outcome compared with medium and large abdominal aortic aneurysms following endovascular aneurysm repair(EVAR). DESIGN: A prospective clinical series of 206 patients undergoing elective EVAR between 1996 and 2001. SETTING: A tertiary care academic health center. PATIENTS: Patients were grouped according to aneurysm size: small (<50 mm), medium (50-60 mm), and large (>60 mm). INTERVENTIONS: Primary EVAR and secondary procedures to secure fixation of the stent graft and surgical conversions. MAIN OUTCOME MEASURES: Aneurysm diameter, endoleaks, and long-term morphologic changes were analyzed postoperatively with 3-dimensional reconstructions of computed tomographic angiograms. RESULTS: Groups were similar in age, comorbidities, and follow-up (mean +/- SD, 32.1 +/- 11.8 months). There were 30 small aneurysms, 92 medium aneurysms, and 84 large aneurysms, with a mean size of 45.1 +/- 3.7 mm, 53.8 +/- 3.1 mm, and 66.1 +/- 6.8 mm, respectively (P<.01). There was no significant difference in proximal neck or iliac artery diameter among the 3 groups. The proximal aortic neck length (28.1 +/- 11.6 mm [small]; 23.9 +/- 11.3 mm [medium]; and 22.1 +/- 11.6 mm [large]; P<.05) was significantly shorter in large aneurysms. Furthermore, there was a significant increase (6% [small]; 15% [medium]; and 21% [large]; P<.05) in angulated necks in large aneurysms. Following treatment, aneurysm diameter remained stable in most patients (83% [small]; 82% [medium]; and 83% [large]), with a mean decrease of 2.0 +/- 6.5 mm, 2.1 +/- 6.1 mm, and 3.7 +/- 7.7 mm in each group, respectively (P =.45). There was no difference in the incidence of endoleaks, aneurysm contraction, or aneurysm expansion based on preoperative aneurysm diameter. Secondary procedures were performed in 5 (20%) of 25, 9 (5.2%) of 170, and 5 (36%) of 11 aneurysms that contracted, remained stable, or expanded, respectively, following EVAR (P<.05). CONCLUSIONS: There is a 15% increase in neck angulation and a 27% decrease in neck length in large compared with small infrarenal abdominal aortic aneurysms, with no difference in outcome. Aneurysms that are stable following EVAR have a significantly lower incidence of requiring secondary procedures.

Duplex scanning after endovascular aneurysm repair: an alternative to computed tomography.

Late complications following endovascular aneurysm repair indicate the need for long-term surveillance. Clinical trials involving endoluminal stent grafts have typically used computed tomography angiography as the main imaging modality for surveillance. However, computed tomography angiography exposes the patient to higher levels of ionizing radiation, nephrotoxic agents, and increased cost compared to duplex ultrasound. Duplex ultrasound scanning has been widely used for surveillance of abdominal aortic aneurysms for many years. It is well established and the procedure of choice for noninvasive imaging of the aorta. It offers the advantages of easy access, decreased cost, no radiation exposure, and no nephrotoxicity. There is little controversy about duplex scanning for preoperative patient evaluation or surveillance of patients with small aneurysms. However, the use and reliability of duplex scanning in the evaluation and surveillance of patients following endovascular repair is controversial. This article will discuss the benefits, techniques, and limitation of duplex ultrasound in the long-term surveillance of endografts following endovascular abdominal aortic aneurysm repair.

Complete abdominal aortic aneurysm thrombosis and obstruction of both common iliac arteries with intrathrombotic pressures demonstrating a continuing risk of rupture: a case report and review of the literature.

INTRODUCTION: Although mural thrombus in an abdominal aortic aneurysm is frequent and its role has been studied extensively, complete thrombosis of an abdominal aneurysm is extremely rare and its natural history in relation to the risk of rupture is not known. The case of a patient with a completely thrombosed infrarenal aneurysm is presented along with a literature review. CASE PRESENTATION: We report the case of a 56-year-old Caucasian man with an infrarenal abdominal aortic aneurysm, presenting at our hospital due to critical ischemia of his right lower limb. Computed tomography and angiography demonstrated complete aneurysm thrombosis and obstruction of both common iliac arteries. CONCLUSION: During the operation, systolic and mean intrathrombotic pressures, measured in different levels, constituted 74.5-90.2% and 77.5-92.5% of systolic and mean intraluminal pressure and 73-88.4% and 76.5-91.3% of systemic pressure, respectively. Our findings show that there may be a continuing risk of rupture in cases of a thrombosed abdominal aortic aneurysm.

Spontaneous arterial recanalization with magnetic resonance angiography evidence: report of a case.

A 27-year-old man was admitted to our hospital for investigation of severe claudication in his right foot. Based on the findings of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), we diagnosed anatomic popliteal artery entrapment syndrome, which was causing a short popliteal artery occlusion. Moreover, a long posterior tibial artery occlusion and a peroneal artery lesion had developed as distal thromboembolic complications of the entrapment. Thus, we planned to perform in situ vein bypass graft for the popliteal occlusion and start thrombolytic treatment for the posterior tibial and peroneal lesions. While contemplating the operation, the patient showed a gradual clinical improvement over the next 2 months. A second MRA showed total arterial recanalization of the right posterior tibial and peroneal arteries, although the popliteal artery was still occluded. Spontaneous lower limb arterial recanalization is a rare phenomenon. To our knowledge, this is the first case of spontaneous arterial recanalization after a distal thromboembolic event caused by popliteal entrapment syndrome.

Subclavian vein thrombosis caused by an unusual congenital clavicular anomaly in an atypical anatomic position.

The optimal surgical management of subclavian vein effort thrombosis remains a dilemma because outcomes after different treatment strategies are only on the basis of small retrospective series. SVT treatment should be on the basis of the cause of thrombosis. Primary effort thrombosis or Paget-Schroetter syndrome frequently necessitates a surgical approach. The type of surgery has to be individualized after careful diagnostic evaluation. We report a congenital clavicular exostosis that had not been identified with chest radiograph and computed tomographic scan that caused SVT in a young woman. This unusual cause of Paget-Schroetter syndrome was treated with a unique approach.

Treatment of axillosubclavian vein thrombosis: a novel technique for rapid removal of clot using low-dose thrombolysis.

PURPOSE: To report successful combined percutaneous mechanical thrombectomy and pharmacological lysis for axillosubclavian vein thrombosis, with rapid clot removal at a single setting using low-dose thrombolysis. CASE REPORTS: Two consecutive patients presented with arm swelling; the diagnosis of axillosubclavian vein thrombosis was confirmed with duplex ultrasound. Both patients were treated percutaneously with the Solera mechanical thrombectomy device, after which 5 mg of tissue plasminogen activator were delivered within approximately 10 minutes via the Trellis infusion catheter to remove any residual thrombus. Completion venography and serial duplex ultrasound scans in follow-up demonstrated widely patent axillosubclavian veins with no residual thrombus in both cases. CONCLUSIONS: Standard treatment of axillosubclavian vein thrombosis may require 12 to 36 hours, with multiple trips to the angiography suite. The novel technique combining mechanical thrombectomy and pharmacological lysis can be performed safely and successfully at a single setting with a small dose of the lytic drug.

How many patients with infrarenal aneurysms are candidates for endovascular repair? The Northern California experience.

PURPOSE: To determine how many patients with abdominal aortic aneurysms (AAA) meet the anatomical selection criteria for AneuRx stent-graft repair in community hospitals of Northern California. METHODS: The records were reviewed of 220 AAA patients (171 men, 49 women) who were considered for endovascular repair by the treating vascular surgeon at 28 community hospitals in Northern California between January and October 2001. Contrast computed tomographic angiography (CTA) and selective arteriography were performed at each institution and reviewed by a centralized, independent image-reading center. Selection criteria determined by the manufacturer and published in the indications for use were applied to each set of imaging studies. The number of patients who met inclusion criteria were recorded, as were the anatomical characteristics of each aneurysm. RESULTS: The mean aneurysm size in the 220 patients was 55.3 +/- 0.7 mm. Among these patients, 122 (55%) were judged to be candidates for endovascular repair and 98 (45%) were considered ineligible. The primary anatomical reason for ineligibility was a short infrarenal neck in 43 (44%) patients, followed by a large proximal neck diameter (25, 25%), iliac aneurysms (10, 10%), extremely tortuous or calcified neck (7, 7%), iliac occlusion (6, 6%), and small distal aortic bifurcation and accessory renal arteries (5, 5%). Four (4%) patients were classified as non-candidates due to poor quality imaging. There was no difference in aneurysm diameter (54.0 +/- 0.8 versus 57.1 +/- 1.2 mm, p=NS) or age (72.2 +/- 1.2 versus 74.6 +/- 2.2 years, p=NS) between candidates and non-candidates. However, proportionally more men (60%) than women (39%) were eligible for endovascular repair with the AneuRx stent-graft (p<0.05). All 122 patients who were considered candidates for endovascular repair were treated, with successful stent-graft placement achieved in 121 (99%). CONCLUSIONS: Fifty-five percent of patients considered for endovascular AAA repair in community hospitals in Northern California met the anatomical selection criteria for the AneuRx stent-graft. Men appeared to be twice as likely to meet the eligibility requirements as women. Unfavorable infrarenal neck anatomy was the primary exclusion criterion for endovascular repair in this community setting.

Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease.

OBJECTIVE: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. METHODS: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V(0)), after addition of substrates (malate and glutamate; (V(SUB)), after addition of adenosine diphosphate (ADP) (V(ADP)), and finally, after adenine nucleotide translocase inhibition with atractyloside (V(AT)). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V(ADP)/ V(AT)). RESULTS: Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 +/- 0.06 vs 0.55 +/- 0.12; P =.09), but V(sub) was significantly lower in patients with PAD compared with control subjects (0.43 +/- 0.07 vs 0.89 +/- 0.20; P <.05), as was V(ADP) (0.69 +/- 0.13 vs 1.24 +/- 0.20; P <.05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 +/- 0.07 vs 0.45 +/- P =.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 +/- 0.10 vs 2.90 +/- 0.20; P <.001). CONCLUSION: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.

Intrasac flow velocities predict sealing of type II endoleaks after endovascular abdominal aortic aneurysm repair.

PURPOSE: The purpose of this study was to determine whether intrasac spectral Doppler flow velocities can predict whether or not a type II endoleak will spontaneously seal and to relate intrasac flow to preoperative branch vessel anatomy. METHODS: Between October 1996 and June 2002, 265 patients with abdominal aortic aneurysms underwent endovascular repair. Patients with less than 24 months of follow-up and type I endoleaks were excluded. Type II endoleaks were confirmed with duplex scan and computed tomographic angiography. Two groups were identified: 14 patients with sealed endoleaks (<6 months) without intervention and 16 patients with persistent endoleaks greater than 6 months and without resolution. Spectral Doppler flow velocities were recorded from endoleaks within the aneurysm sac. RESULTS: The two groups were similar in age, demographics, and aneurysm morphology. The mean follow-up times were 29.9 +/- 7.9 months for sealed endoleaks and 30.2 +/- 8.6 months for persistent endoleaks (P = not significant). Spectral Doppler velocities were significantly lower in patients with sealed endoleaks compared with persistent endoleaks (75.5 +/- 78.8 cm/s versus 138.2 +/- 36.2 cm/s; P <.01). Patients with sealed endoleaks and low (<100 cm/s) intrasac Doppler velocities had significantly fewer patent inferior mesenteric arteries (43% versus 81%; P <.01), a smaller inferior mesenteric artery (5.6 +/- 1.8 mm versus 7.2 +/- 1.3 mm; P <.01), and fewer paired lumbar arteries (1.3 +/- 0.8 versus 2.4 +/- 0.6; P <.0001) compared with those with persistent endoleaks and high (>100 cm/s) intrasac flow velocities. Three patients with sealed endoleaks had Doppler velocities of 200 cm/s or greater. However, the diameter of the inferior mesenteric artery in these patients was 4 mm or less with no visualized lumbar arteries before surgery. Aneurysm diameter(-4.6 +/- 5.6 mm) and volume (-0.9 +/- 45.2 mL) decreased in patients with sealed endoleaks. Aneurysm diameter (1.8 +/- 4.9 mm) and volume (18.5 +/- 33.9 mL) increased slightly in patients with persistent endoleaks (P <.05). No ruptures or conversions occurred in any patient. Secondary interventions to treat type II endoleaks were unsuccessful in six of 16 patients (38%) with persistent endoleaks. CONCLUSION: Intrasac Doppler velocities can be used to predict whether a type II endoleak will spontaneously seal. High-velocity type II endoleaks are related to preoperative large branch vessel diameter and number and are resistant to endovascular treatment.

Duplex ultrasound criteria for defining the severity of carotid stenosis.

Duplex ultrasound scan (DUS) criteria for grading >50% carotid artery stenosis is typically divided into broad categories such as 50-79% stenosis, 80-99% stenosis, and occlusion. The purpose of this study is to validate DUS criteria for stratifying 50 to 100% carotid stenosis into 10% intervals using digital substraction cerebral angiography (DSCA) as the standard of comparison. Between 1996 and 2001, 163 patients were evaluated with duplex ultrasound and angiography. A total of 326 carotid arteries were studied using DUS in an accredited ICAVL vascular laboratory. Threshold velocity criteria for determining the degree of carotid stenosis was defined according to seven categories: <50%, 50-59%, 60-69%, 70-79%, 80-89%, 90-99%, and occlusion. Treatment decisions were based on the angiographic findings. In cases where the degree of stenosis as defined by duplex velocity criteria did not correlate with angiographically defined stenosis, each record was reviewed to determine whether the angiographic findings altered the surgeon's treatment decision. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for DUS-defined degree of stenosis as compared to angiographically defined stenosis were determined. There was a high correlation (R = 0.96) between duplex scan and angiography in 93% (302/326) of the cases. Clinical management was altered in only 3% (10/326) of the cases because of the results of angiography. The DUS velocity criteria to grade the severity of carotid disease in 10% intervals is reliable and accurate. Clinical management of patients with carotid stenosis can be based solely on carotid DUS in 97% of patients considered for treatment of carotid artery disease.