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Biomedical subjects

Alan B Lumsden

Publications and source records attributed to Alan B Lumsden.

At least 37 records · Page 2Linked to original sources
PubMed2006

IMA clipping for a type ii endoleak: combined laparoscopic and endovascular approach.

We describe herein a combined laparoscopic and endovascular approach to treat a type II endoleak due to retrograde flow in the patent inferior mesenteric artery (IMA). A 61-year-old gentleman presented with enlarging aneurysm sac confirmed on computed tomography scan evaluation after elective endovascular repair of an infrarenal abdominal aortic aneurysm. A combined laparoscopic and endovascular approach was used. After distal IMA was identified and marked with a clip laparoscopically, on-table angiography showed a proximal left colic branch and persistent flow in the IMA. Therefore, further laparoscopic exploration was performed by dissection along the distal branch. The origin of IMA was then located and subsequently sealed with 2 surgical clips. The completion angiography confirmed the proper position of the surgical clips and absence of endoleak. Our case demonstrated useful role of endovascular techniques in identifying the origin of IMA during laparoscopic approach for treating type II endoleak.

Aortic Aneurysm, Abdominal↗
PubMed2006

Medical management of peripheral arterial disease: a therapeutic algorithm.

Over half of the people with peripheral arterial disease (PAD) may be asymptomatic. The most common symptom of mild-to-moderate PAD is intermittent claudication, present in about one third of symptomatic patients. Patients with intermittent claudication often have severely impaired functional status. Despite the high prevalence of the disease and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than are those being treated for coronary artery disease. The goals of treatment are to prevent progression of systemic atherosclerosis and its associated morbidity and mortality, to prevent limb loss, and to improve functional capacity for symptomatic patients. For claudicating patients, medical management includes symptomatic treatment with cilostazol or pentoxifylline. For all patients, it is equally important to pursue risk reduction through exercise programs and promotion of smoking cessation, as well as with the use of statins, antiplatelet therapies, antithrombotic strategies, angiotensin-converting-enzyme inhibitors, beta-blockers, and attention to homocysteine levels. Because not all patients are symptomatic, medical management of peripheral arterial disease may proceed along an algorithmic pathway that recognizes 3 types of patients: those requiring risk reduction only, symptomatic patients with minimal lifestyle limitation, and symptomatic patients with significant lifestyle impairment.

Adrenergic beta-Antagonists↗
PubMed2006

In situ reconstruction with cryopreserved arterial allografts for management of mycotic aneurysms or aortic prosthetic graft infections: a multi-institutional experience.

We designed this study to evaluate a multi-institutional experience regarding the efficacy of cryopreserved aortic allografts in the treatment of infected aortic prosthetic grafts or mycotic aneurysms. We reviewed clinical data of all patients from 4 institutions who underwent in situ aortic reconstruction with cryopreserved allografts for either infected aortic prosthetic graft or mycotic aneurysms from during a 6-year period. Relevant clinical variables and treatment outcomes were analyzed. A total of 42 patients (37 men; overall mean age 63 +/- 13 years, range 41-74 years) were identified during this study period. Treatment indications included 34 primary aortic graft infections (81%), 6 mycotic aneurysms (22%), and 2 aortoenteric erosions (5%). Transabdominal and thoracoabdominal approaches were used in 38 (90%) and 4 patients (10%), respectively. Staphylococcus aureus was the most commonly identified organism (n=27, 64%). Although there was no intraoperative death, the 30-day operative mortality was 17% (n=7). There were 21 (50%) nonfatal complications, including local wound infection (n=8), lower-extremity deep venous thrombosis (n=5), amputation (n=6), and renal failure requiring hemodialysis (n=2). The average length of hospital stay was 16.4 +/- 7 days. During a mean follow-up period of 12.5 months, reoperation for allograft revision was necessary in 1 patient due to graft thrombosis (6%). The overall treatment mortality rate was 21% (n=9). In situ aortic reconstruction with cryopreserved allografts is an acceptable treatment method in patients with infected aortic prosthetic graft or mycotic aneurysms. Our study showed that mid-term graft-related complications such as reinfection or aneurysmal degeneration were uncommon.

Adult↗
PubMed2006

Mouse models of neointimal hyperplasia: techniques and applications.

Neointimal hyperplasia is a major cause of the failure in vascular reconstructive procedures such as angioplasty, vascular stenting, small caliber vascular graft, and vein graft. However, the underlying molecular mechanisms are not yet fully understood. The study of neointimal hyperplasia has relied heavily on the use of experimental animal models. Recent development in gene manipulation techniques in mice offers a unique opportunity to unravel the molecular basis of the neointimal response at the genetic level, which is critical to develop new strategies to prevent human neointimal hyperplasia. Several mouse models for studying neointimal hyperplasia have recently been established including blood-flow cessation, mechanical injury, and vein bypass graft. In an attempt to elaborate these models, this review highlights the characteristics, advantages, disadvantages, and applications of these mouse models in vascular disease. In addition, the difference between mouse models and human lesions is discussed. Thus, this review provides updated information and helps vascular surgeons and other vascular biologists in selecting appropriate mouse models for their research on neointimal hyperplasia.

Animals↗
PubMed2005

Nitrotyrosine and chlorotyrosine: clinical significance and biological functions in the vascular system.

The heme-containing enzyme myeloperoxidase (MPO) is both present and active in inflammatory conditions. This enzyme is potentiated by its formation of multiple inflammatory mediators. The two most common mediators are the modified tyrosines: nitrotyrosine and 3-chlorotyrosine. Along with other modified tyrosines, these molecules have been found to be elevated in atherosclerosis, lung disease, sepsis, vasculitis, and other inflammatory diseases. By treating some of these diseases, the levels of modified tyrosines have been shown to decrease. There have been a wide range of animal models designed to study the in vivo effects of these tyrosine molecules. In addition, there are also several reports in the literature of the in vitro actions of modified tyrosine molecules demonstrated by various cell-culture models. The purpose of this review is to evaluate the clinical significance and biological functions of these modified tyrosine molecules in atherosclerosis as well as a variety of other inflammatory conditions. It is timely information because of their association with diseases as well as lack of overview of their molecular actions. This review will focus on the formation, clinical significance, and animal and cell-culture models of these important molecules.

Animals↗
PubMed2005

Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease: mediators of endothelial dysfunction and atherosclerosis.

Lysophosphatidylcholine (LPC) is the major component of oxidized low density lipoprotein (oxLDL) and it has the ability to initiate or amplify several steps in atherogenesis due to its ability to impair endothelium-dependent vasorelaxation, enhance endothelial proliferation and permeability, stimulate adhesion and activation of lymphocytes, initiate chemotaxis of macrophages, impair migration and proliferation in vascular smooth muscle cells (SMCs), and modify platelet aggregation and coagulation pathways. For many of the LPC-induced effects, protein kinase C-dependent pathways have been implicated. In addition, modulation of ion current activity in the cell membrane, binding to a specific oxLDL receptor or to G-protein coupled receptors, as well as amplification of a highly oxidative state have all been postulated as likely mediating mechanisms. Secretory phopholipase A(2)-II (sPLA(2)-II) is one of the enzymes responsible for LPC production. sPLA(2)-II has been recently recognized as an independent risk factor for coronary artery disease. sPLA(2)-II favors the formation of bioactive lipids, stimulates SMC proliferation, activates macrophages enhancing lipid core formation and cytokine secretion, and binds to proteoglycans in the vessel wall matrix promoting lipid fusion and accumulation. The non-catalytic atherogenic effects of sPLA(2)-II are thought to be related to binding to an M-type receptor. Commonly used medications have been shown to decrease sPLA(2)-II activity generating a legitimate interest in the effects of the sPLA(2)-II pharmacologic antagonism. LPC and sPLA(2)-II are two very important mediators in atherosclerosis. Further research is warranted to clarify the cellular and molecular mechanisms that underlie their actions and to correlate in vitro data with clinical observations.

Animals↗
PubMed2005

Effects of 5 HIV protease inhibitors on vasomotor function and superoxide anion production in porcine coronary arteries.

HIV protease inhibitors (PIs) have been implicated to cause cardiovascular complications. Previous studies demonstrated that the PI ritonavir (RTV) caused endothelial dysfunction in porcine arteries. This study investigated and compared the effects of 5 commonly used PIs on vasomotor function, endothelial nitric oxide synthase (eNOS) expression, and oxidative stress in porcine coronary arteries. Vessel rings were incubated with 15 microM of RTV, amprenavir (APV), saquinavir (SQV), indinavir (IDV), or nelfinavir (NFV) for 24 hours. Vasomotor function was studied using a myograph system. The contractility of the rings was significantly reduced for RTV and SQV. In response to bradykinin at 10(-5) M, the endothelium-dependent relaxation was significantly reduced for RTV, APV, and SQV. The eNOS mRNA levels were significantly reduced for RTV, APV, and SQV. Furthermore, the superoxide anion (O(2)(-)) levels of the vessels were significantly increased for RTV and APV. It was found that nitric oxide production was decreased, whereas the level of nitrotyrosine proteins was increased in RTV-treated vessels. Furthermore, antioxidant seleno-L-methionine (SeMet) reversed RTV-induced O(2)(-) production and vasomotor dysfunction. Thus, the HIV PIs RTV, APV, and SQV at 15 microM have more potent in vitro effects on vasomotor dysfunction, eNOS downregulation, and O(2)(-) production than IDV and NFV. The antioxidant SeMet can block these adverse effects of RTV. The results suggest that antioxidant therapy may have applications for controlling PI-associated cardiovascular complications.

Animals↗
PubMed2005

Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease.

Adipose tissue has recently emerged as an active endocrine organ that secretes a variety of metabolically important substances, collectively called adipocytokines or adipokines. In this review we summarize the effects of the adipokines leptin, adiponectin, and resistin on the vasculature and their potential role for pathogenesis of vascular disease. Leptin is associated with arterial wall thickness, decreased vessel distensibility, and elevated C reactive protein (CRP) levels. Leptin possesses procoagulant and antifibrinolytic properties, and it promotes thrombus and atheroma formation, probably through the leptin receptors by promoting vascular inflammation, proliferation, and calcification, and by increasing oxidative stress. Research for development of pharmacologic antagonism for the leptin receptor is currently under way. Adiponectin inhibits the expression of the adhesion molecules ICAM-1, VCAM-1, and P selectin. Therefore, it interferes with monocyte adherence to endothelial cells and their subsequent migration to the subendothelial space, one of the initial events in the development of atherosclerosis. Adiponectin also inhibits the transformation of macrophages to foam cells in vitro and decreases their phagocytic activity. Resistin, discovered in 2001, represents the newest of the adipokines and was named for its ability to promote insulin resistance. Resistin increases the expression of the adhesion molecules VCAM-1 and ICAM-1, up-regulates the monocyte chemoattractant chemokine-1, and promotes endothelial cell activation via ET-1 release. Although many aspects of its function need further clarification, it appears that resistin will add significantly to our knowledge of the pathophysiology of vascular disease and the metabolic syndrome.

Adiponectin↗
PubMed2005

Comparison of 15 different stents in superficial femoral arteries by high resolution MRI ex vivo and in vivo.

PURPOSE: To evaluate the MRI compatibility of 15 different commercially available, new generation, U.S. Food and Drug Administration (FDA)-approved stents suitable for deployment in superficial femoral arteries (SFAs), and to identify the ones that permit MRI to visualize the wall and lumen of stented arteries with sufficient spatial and contrast resolution to quantify restenosis after stent placement. MATERIALS AND METHODS: A total of 13 nitinol stents and two stainless-steel stents were placed in excised cadaveric SFAs and imaged by MRI at 1.5 T ex vivo. The images were evaluated qualitatively for the presence of artifacts and for the effects of the stent on image contrast, and quantitatively for the effect on signal-to-noise ratio (SNR) of the lumen of the artery inside the stent compared to the SNR of the fluid outside the artery. A nitinol stent was placed in the SFA of a 60-year-old man and imaged at 1.5 T in vivo. RESULTS: Both the vessel wall and the lumen could be visualized in cadaveric SFAs containing either the Absolute nitinol stent, the Dynalink nitinol stent, or the aSpire nitinol-covered stent. Their inside stent/outside stent SNR was 0.7, 0.8, and 0.8, respectively. The other 10 nitinol stents tested obscured the lumen but did not cause major image shape artifacts. Both stainless-steel stents tested, the WallGraft and WallStent, completely obscured the lumen and caused significant distortion of the image shapes. When the Dynalink stent was inserted into a highly stenosed SFA in vivo, the image showed a dark expanded eccentric lumen, circumscribed by a medium intensity band containing the stent. CONCLUSION: MRI can be used to visualize both the lumen and wall of SFAs containing selected nitinol stents ex vivo and in vivo. These results suggest that MRI can be used to monitor restenosis in stents placed in the femoral arterial bed.

Alloys↗
PubMed2005

Roles of hemodynamic forces in vascular cell differentiation.

The pulsatile nature of blood flow is a key stimulus for the modulation of vascular cell differentiation. Within the vascular media, physiologic stress is manifested as cyclic strain, while in the lumen, cells are subjected to shear stress. These two respective biomechanical forces influence the phenotype and degree of differentiation or proliferation of smooth muscle cells and endothelial cells within the human vasculature. Elucidation of the effect of these mechanical forces on cellular differentiation has led to a surge of research into this area because of the implications for both the treatment of atherosclerotic disease and the future of vascular tissue engineering. The use of mechanical force to directly control vascular cell differentiation may be utilized as an invaluable engineering tool in the future. However, an understanding of the role of hemodynamics in vascular cell differentiation and proliferation is critical before application can be realized. Thus, this review will provide a current perspective on the latest research and controversy behind the role of hemodynamic forces for vascular cell differentiation and phenotype modulation. Furthermore, this review will illustrate the application of hemodynamic force for vascular tissue engineering and explicate future directions for research.

Animals↗
PubMed2005

A comparison of carotid artery stenting with neuroprotection versus carotid endarterectomy under local anesthesia.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke in patients with high-grade carotid artery stenosis. Despite the known impact of type of anesthesia on outcome after CEA, none of the current studies comparing CEA with CAS addresses the effect of anesthetic choice on perioperative events. In this study, we compare our results of distally protected CAS versus CEA under local anesthesia. METHODS: Clinical data of 345 patients who underwent 372 procedures for carotid artery occlusive disease over a 36-month were retrospectively collected for this analysis. Distal embolic protection was used in CAS procedures. All procedures, both CEA (n = 221, 59%) and CAS (N = 152, 41%), were performed under local anesthesia. The primary outcome measure was aggregate 30-day major ipsilateral stroke and/or death. Follow-up serial Duplex ultrasound examinations were performed. RESULTS: Both patient cohorts were similar in terms of demographic and risk factors, with the exception of a higher incidence of coronary artery disease in the CAS group (59% versus 30%, P <.05). The 30-day stroke and death rates were 3.2% (CAS) and 3.7% (CEA) (P = not significant). Cranial nerve injury only occurred in the CEA patients (2.3%). Perioperative hemodynamic instability was more common among patients in the CAS group (11.9% versus 4.1%, P <.05). CONCLUSIONS: Percutaneous carotid stenting with neuroprotection provides comparable clinical success to CEA performed under local anesthetic. Further studies are warranted to validate the long-term efficacy of CAS and to elucidate patient selection criteria for endovascular carotid revascularization.

Aged↗
PubMed2005

Carotid artery stenting with neuroprotection: assessing the learning curve and treatment outcome.

PURPOSE: Carotid artery stenting (CAS) has emerged as an acceptable treatment alternative in high-risk patients with carotid stenosis. The purpose of this study was to assess the effect of the learning curve on treatment complications and the clinical outcomes of CAS. METHODS: Clinical variables and treatment outcomes of 200 consecutive CAS procedures in 182 patients (mean age 72 years) with carotid stenosis > or = 70% during a 40-month period were analyzed. Four sequential groups (groups I, II, III, and IV) of 50 consecutive interventions were compared with regard to technical success, periprocedural complications, and treatment outcomes. RESULTS: Treatment indications and relevant risk factors were similar among the 4 groups. The overall technical success and combined 30-day stroke and death rates were 98% and 2.5%, respectively. An increase in the technical success rate was noted in the latter 3 groups compared with group I (P < .05). Total procedural time and contrast volume were significantly higher in group I compared with the latter 3 groups (P < .05). The intraoperative anticoagulation regimen was changed from intravenous heparin combination to bivalirudin after the first 54 patients, which resulted in decreased bleeding complications in groups III and IV (P = 0.03) compared with the first group. The 30-day stroke and death rate in groups I and II were 8% and 2%, respectively, and was decreased significantly in groups III and IV (0% and 0%, respectively, P < .05). A Cox regression model identified procedural volume (P = .03) as a predictor of decreased complication rate. CONCLUSIONS: CAS with neuroprotection can provide excellent treatment outcomes. Our experience demonstrates a procedure-associated learning curve as evidenced by decreased procedure-related complications, fluoroscopic time, and contrast volume occurring with increased physician experience. Procedural success was also enhanced partly by endovascular device refinement and an improved anticoagulation regimen. Successful CAS outcomes can be achieved once physicians overcome the initial procedure-related learning curve.

Aged↗
PubMed2005

Curcumin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine coronary arteries.

BACKGROUND: HIV protease inhibitor ritonavir (RTV) is associated with many cardiovascular complications and causes vascular dysfunction through oxidative stress. In the present study, we determined the effects of RTV and curcumin (a pigment derived from turmeric) on porcine coronary arteries. STUDY DESIGN: Artery rings were incubated with 15 microM concentration of RTV and curcumin (5 or 10 microM) for 24 hours. Vasomotor function was studied with a myograph tension system. Endothelial nitric oxide synthase (eNOS) mRNA and protein levels were studied using real-time polymerase chain reaction, Western blot, and immunohistochemistry. Nitric oxide was measured using Griess assay. Superoxide anion levels were determined by lucigenin enhanced chemiluminescence. RESULTS: RTV considerably reduced vessel contraction by 71%, endothelium-dependent relaxation by 59%, and endothelium-independent relaxation by 52%, as compared with controls. Curcumin effectively blocked RTV-induced vasomotor dysfunction. RTV-treated arteries showed substantial reductions of eNOS mRNA by 77%, eNOS protein by 72%, and nitric oxide release by 37% as compared with controls. The RTV plus curcumin-treated vessels showed substantial increases of eNOS and nitric oxide levels as compared with the RTV-treated vessels. Finally, there was a 47% increase of superoxide anion production in the RTV-treated vessels as compared with controls. Again, curcumin effectively reversed this effect of RTV. CONCLUSIONS: HIV protease inhibitor RTV impairs vasomotor functions, reduces eNOS expression and nitric oxide release, and increases oxidative stress in porcine coronary arteries. Curcumin effectively blocks these detrimental effects of RTV.

Animals↗
PubMed2005

Effects of cyclophilin A on cell proliferation and gene expressions in human vascular smooth muscle cells and endothelial cells.

BACKGROUND: Cyclophilin A (CypA) is a cytosolic protein which involves many biological functions including immune modulation, cell growth, tumorigenesis, and vascular disease. The objective of this study was to determine the effect of CypA on cell proliferation and several gene expressions in human endothelial cells and vascular smooth muscle cells. METHODS: Human coronary artery endothelial cells (HCAEC), human lung microvascular endothelial cells (HMVEC-L), and human aorta smooth muscle cells (HAoSMC) were used in this study. Cells were treated with 10 nM CypA for 24 h. The cell proliferation was determined by [3H]thymidine incorporation. The mRNA levels of 13 genes including CD147 (receptor for CypA), PDGF-BB, endothelin-1 (ET-1), vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, VEGFR-3, neuropilin-1 (NRP-1), NRP-2, eNOS, iNOS, nNOS, ICAM-1, and PECAM-1 were semiquantitatively determined by real time RT-PCR as standardized with a house keeping gene beta-actin. RESULTS: CypA significantly increased cell proliferation of HAoSMC and HMVEC-L by 31% and 45%, respectively, as compared to controls, but had no effect on HCAEC. Blocking CD147 did not affect the mitogenic action of CypA. In addition, CypA also significantly increased the mRNA expression of CD147 by 43% and VEGFR-2 by 65% in HAoSMCs (P < 0.05, t test). HAoSMCs expressed much higher CD147 and neuropilin-1 (NRP-1) mRNA than HMVECs-L and HCAECs (P < 0.017, ANOVA). Furthermore, CypA increased ET-1 mRNA by 22% and VEGFR-1 mRNA by 23% in HMVECs-L, but had limited effects on HCAECs. HMVECs-L had much higher expressions of PDGF-BB, ET-1, VEGFR-2, VEGFR-1, VEGFR-3, and NRP-2 than HAoSMCs and HCAECs (P < 0.017, ANOVA). By contrast, HCAECs had much higher ICAM-1 mRNA levels than HMVECs-L and HAoSMCs (P < 0.017, ANOVA). CONCLUSIONS: These data demonstrate that CypA has a mitogenic effect on HAoSMCs and HMVECs-L, but not HCAECs. CD147 may not mediate the action of CypA. In addition, CypA substantially alters the mRNA levels of several key genes in human vascular cells, indicating potential multifunctional roles of CypA in vascular system. Furthermore, this study provides several new aspects of gene expressions in vascular cells.

Aorta↗