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Biomedical subjects

Lars Svensson

Publications and source records attributed to Lars Svensson.

9 recordsLinked to original sources

Transapical aortic valve implantation: an animal feasibility study.

BACKGROUND: Percutaneous aortic valve implantation has recently been performed in nonsurgical patients with severe aortic stenosis. Retrograde valve delivery has been problematic because of the size of the delivery system and concomitant peripheral vascular disease. We investigated a minimally invasive approach through the left ventricular apex for antegrade placement of a device-deliverable valve. METHODS: Transapical aortic valve implantation was performed using a 23-mm equine valve mounted on a stainless steel stent in 24 swine (weight range, 35 to 45 kg). A limited or full sternotomy approach was used to access the apex of the heart. The crimped valve was introduced through a sheath in the left ventricular apex. Fluoroscopy and echocardiography were used for guidance. Deployments were performed on the beating heart either with ventricular unloading using femoral extracorporeal circulation or rapid ventricular pacing. RESULTS: All valves were successfully delivered at the selected target site with acceptable visualization of the noncalcified aortic annulus. Valve migration occurred during eight deployments (two distal and six retrograde) secondary to persistent cardiac output, unfavorable annular anatomy, and dislodgement by the delivery catheter. Exact positioning of the nonmigrated valves at the aortic annulus was examined by necropsy of all animals at the end of the procedures. Paravalvular leak was noted in 14 of 18 (77.8%) valves remaining in situ. CONCLUSIONS: The transapical approach was used for the successful antegrade placement of a stented valve, obviating the technical problems associated with a large delivery system transiting the peripheral vascular system. Stent design contributing to paravalvular leak remains problematic.

Animals↗

Invited commentary.

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Aortic Dissection↗

Beyond the aortic bifurcation: branched endovascular grafts for thoracoabdominal and aortoiliac aneurysms.

OBJECTIVES: To evaluate the use of novel technology to treat complex aortic aneurysms involving branches that provide critical end-organ blood supply. METHODS: A prospective study was conducted in patients with thoracoabdominal, suprarenal, or common iliac aneurysms (TAA, SRA, or CIA) at high risk for open surgical repair. An endovascular graft using the Zenith platform was customized to fit patient anatomy (TAA or SRA) and combined with Jomed balloon-expandable stent-grafts. Prefabricated hypogastric branches were used with a Zenith abdominal aortic aneurysm (AAA) or Fluency self-expanding fenestrated device in conjunction with a self-expanding stent-graft. Analyses were conducted in accordance with the endovascular aneurysm reporting standards document. Follow-up studies occurred at discharge, 1, 6, and 12 months, and included computed tomography and duplex ultrasound scans, and flat plate radiography. RESULTS: Fifty patients were treated (9 TAA, 20 SRA, 21 CIA). The mean aneurysm size was 7.6 cm (TAA), 7.2 cm (SRA), and 6.1 cm AAA size associated with a mean CIA size of 3.8 cm. Bilateral CIA aneurysms were present in 86% (18/21) of patients with CIA aneurysms. Perioperative mortality was 2% (1/50) and resulted from a myocardial infarction after a planned conduit and iliac endarterectomy required for device access. Five late deaths occurred (2 TAA, 2 SRA, 1 CIA), three of which (2 TAA, 1 SRA) were aneurysm related. Failure to access internal iliac arteries occurred in three cases, and two late hypogastric branch thromboses occurred. No visceral branches were lost acutely or occluded during follow-up. Sac shrinkage (>5 mm) was noted in 65% of patients at 6 months and in all patients (10/10) by 12 months. There were no ruptures or conversions, but nine patients required secondary interventions. CONCLUSIONS: Branch vessel technology has made it technically feasible to preserve critical end-organ perfusion in the setting of CIA, SRA, and TAA aneurysms. The relatively low acute mortality rate and lack of short-term branch vessel loss are encouraging and merit further investigation. These advances have the potential to markedly diminish the complications associated with conventional management of complex aneurysms.

Angioplasty↗

Hybrid approaches to thoracic aortic aneurysms: the role of endovascular elephant trunk completion.

BACKGROUND: Thoracic aortic aneurysm affecting the arch and proximal descending thoracic aorta requires 2-stage repairs that include proximal elephant trunk graft placement and completion of thoracic or thoracoabdominal repair. The application of endovascular grafting to complete the proximal procedure avoids a thoracotomy and may improve the morbidity and mortality of the patient population at risk. METHODS AND RESULTS: A retrospective review of 399 thoracic endovascular grafts at our institution between 2000 and 2004 identified 22 patients who required elephant trunk and endovascular completion. Three patients underwent mesenteric bypass in addition to their proximal repairs. Mean follow-up was 10 months (range 1 to 42 months); there were no ruptures, and all patients returned for follow-up. Technical success was achieved in all patients. The 1-, 12-, and 24-month mortality rates (by Kaplan-Meier analysis) were 4.5%, 15.8%, and 15.8%, respectively. Caudal migration of the endograft occurred in 1 patient, and all but 2 aneurysms decreased or remained stable in size. The 2 patients with growth included a type III endoleak (which resolved after treatment) and pressurization through an expanded PTFE stentgraft. Three cases of transient paraparesis occurred (all in patients requiring mesenteric bypass or abdominal aortic aneurysm repair), and there were no paraplegias or strokes. CONCLUSIONS: Endovascular completion of elephant trunks is feasible and can be accomplished with minimal mortality. Meticulous imaging follow-up is required to detect persistent aneurysm pressurization and to verify the integrity of the repair. Improvements in implant design and delivery systems will further simplify the second-stage portion of these complex aneurysm repairs.

Aorta, Thoracic↗

Relapsing polychondritis, induced in mice with matrilin 1, is an antibody- and complement-dependent disease.

Relapsing polychondritis is an autoimmune disease that affects cartilage in the ear, nose, and respiratory tract. A pathogenic immune response has been proposed and antibodies to several cartilage proteins are detected in sera from these patients. To investigate the role of the humoral immune response in relapsing polychondritis, we used the matrilin-1-induced relapsing polychondritis model. Mice deficient of B cells (muMT) and mice congenic at the complement factor 5, were immunized with matrilin-1, a cartilage-specific protein mainly detected in the tracheal cartilage. To investigate the binding properties and tissue selection of matrilin-1-specific antibodies we produced matrilin-1-specific B-cell hybridomas. Although 83% of the micro MT heterozygous mice developed respiratory distress and erosive chondritis in the respiratory tract, none of the B-cell-deficient mice were susceptible to disease. In addition, we show that complement factor 5 is important for the induction of matrilin-1-induced relapsing polychondritis. Monoclonal matrilin-1-specific antibodies injected into neonatal mice bound specifically to cartilage of the respiratory tract and adult B-cell-deficient mice injected with the same antibodies developed erosive chondritis in the respiratory tract. We conclude that relapsing polychondritis can be mediated by a pathway involving tissue-specific antibodies and complement activation.

Animals↗

A new CT method for measuring cup orientation after total hip arthroplasty: a study of 10 patients.

BACKGROUND: It is difficult to assess the orientation of the acetabular component on routine radiographs. We present a method for determining the spatial orientation of the acetabular component after total hip arthroplasty (THA) using computed tomography. PATIENTS AND METHODS: Two CT-scans, 10 min apart, were obtained from each of 10 patients after THA. Using locally developed software, two independent examiners measured the orientation of the acetabular component in relation to the pelvis. The measurements were repeated after one week. To be independent of the patient position during scanning, the method involved two steps. Firstly, a 3D volumetric image of the pelvis was brought into a standard pelvic orientation, then the orientation of the acetabular component was measured. The orientation of the acetabular component was expressed as operative anteversion and inclination relative to an internal pelvic reference coordinate system. To evaluate precision, we compared measurements across pairs of CT volumes between observers and trials. RESULTS: Mean absolute interobserver angle error was 2.3 degrees for anteversion (range 0-6.6 degrees), and 1.1 degrees for inclination (range 0-4.6 degrees). For interobserver measurements, the precision, defined as one standard deviation, was 2.9 degrees for anteversion, and 1.5 degrees for inclination. A Student's t-test showed that the overall differences between the examiners, trials, and cases were not significant. Data were normally distributed and were not dependent on examiner or trial. INTERPRETATION: We conclude that the implant angles of the acetabular component in relation to the pelvis could be detected repeatedly using CT, independently of patient positioning.

Adult↗

Collagen type II-specific monoclonal antibody-induced arthritis in mice: description of the disease and the influence of age, sex, and genes.

Transfer of collagen type II (CII)-specific monoclonal antibodies induces an acute form of arthritis (collagen type II antibody-induced arthritis, CAIA) in naïve mice. Arthritis was induced using a pair of monoclonal antibodies M2139 and CIIC1, binding to J1 and C1(I) epitopes of CII, respectively. Thereafter, lipopolysaccharide injection was used to increase the incidence and severity of the disease. This model was used to investigate the effect of genes, age, and sex as well as effector cells in the end-stage effector phase of arthritis pathogenesis. Injection of a single monoclonal antibody induced arthritis only after lipopolysaccharide stimulation. CAIA showed differences in disease penetration among the susceptible strains indicating the importance of non-major histocompatibility complex genes on the antibody effector pathway. B-cell-deficient mice were susceptible to CAIA and in some genetic backgrounds B-cell deficiency leads to enhanced arthritis. Histology of the affected paws revealed massive infiltrations of neutrophils along with bone and cartilage erosion, pannus formation, and fibrin deposition. Depletion of neutrophils significantly reduced the incidence and severity of the disease. CAIA susceptibility increased with age. Males were more susceptible than females and estrogen treatment decreased the development of arthritis. We conclude that CAIA is an acute arthritis triggered by antibody binding and neutrophils bypassing immune activation but with many characteristics in common with collagen-induced arthritis.

Age Factors↗

IL-4-deficient mice develop less acute but more chronic relapsing collagen-induced arthritis.

Rheumatoid arthritis as well as collagen-induced arthritis (CIA) is thought to involve T cell autoimmunity of the Th1 type and the Th2 cytokine IL-4 has been proposed to play a suppressive role. To exclude a possible skewing role of the mycobacteria used in the complete Freund's adjuvant (CFA) we induced CIA with type II collagen (CII) in incomplete Freund's adjuvant (IFA). Our results show that IL-4 deficiency leads to a lesser susceptibility to arthritis and lower B and T cell responses if induced with CII/IFA but not if induced with CII/CFA. In addition, IL-4-deficient mice were less susceptible to arthritis induced with monoclonal anti-CII antibodies. However, mice immunized with CII/IFA later developed a chronic relapsing disease, which was promoted by IL-4 deficiency. We conclude that IL-4 plays different roles depending on the type of adjuvant used and the phase (acute or chronic) of the clinical disease.

Acute Disease↗

A comparative analysis of B cell-mediated myelin oligodendrocyte glycoprotein-experimental autoimmune encephalomyelitis pathogenesis in B cell-deficient mice reveals an effect on demyelination.

We have investigated the role of B cells in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) using B cell-deficient mice muMT) and mice bearing the X-linked immunodeficiency (xid). The mice were immunized with MOG(1-125 )in complete Freund's adjuvant but without use of pertussis toxin. B cell-deficient muMT mice on different genetic backgrounds (C57BL/10 and DBA/1 strains) developed EAE, although with a reduced clinical severity. Histological analyses revealed decreased demyelination in the central nervous system while the influx of inflammatory cells was similar or only slightly reduced as compared to B cell-sufficient control mice. Xid mice on the DBA/1 background also developed disease with a reduced disease severity. The anti-MOG antibody response in the xid mice was decreased, while the T cell response to MOG was unaffected. We thus demonstrate that B cells are not critical for the development of MOG-induced EAE but contribute to the severity. The contribution of B cells to pathogenesis appears to be mainly through demyelination rather than through inflammation.

Animals↗