Selective and marked decrease of complement receptor C5aR2 in human thoracic aortic aneurysms: a dysregulation with potential inflammatory effects.

Objective: The aetiology of thoracic aortic aneurysm (TAA) is largely unknown, but inflammation is likely to play a central role in the pathogenesis. In this present study, we aim to investigate the complement receptors in TAA. Methods: Aortic tissue and blood from 31 patients with non-syndromic TAA undergoing thoracic aortic repair surgery were collected. Aortic tissue and blood from 36 patients with atherosclerosis undergoing coronary artery bypass surgery or aortic valve replacement were collected and served as control material. The expression of the complement anaphylatoxin receptors C3aR1, C5aR1 and C5aR2 in aortic tissue were examined by quantitative RT-PCR and C5aR2 protein by immunohistochemistry. Colocalisation of C5aR2 to different cell types was analysed by immunofluorescence. Complement activation products C3bc and sC5b-9 were measured in plasma. Results: Compared with controls, TAA patients had substantial (73%) downregulated gene expression of C5aR2 as seen both at the mRNA (p=0.005) level and protein (p=0.03) level. In contrast, there were no differences in the expression of C3aR1 and C5aR1 between the two groups. Immunofluorescence examination showed that C5aR2 was colocalised to macrophages and T cells in the aortic media. There were no differences in the degree of systemic complement activation between the two groups. Conclusion: Our findings suggest downregulation of the C5aR2, regarded to act mainly anti-inflammatory, in electively operated TAA as compared with non-aneurysmatic aortas of patients with aortic stenosis and/or coronary artery disease. This may tip the balance towards a relative increase in the inflammatory responses induced by C5aR1 and thus enhance the inflammatory processes in TAA.

SNF472, a novel anti-crystallization agent, inhibits induced calcification in an in vitro model of human aortic valve calcification.

The purpose of the present study was to investigate whether SNF472, the hexasodium salt of myo-inositol hexaphosphate (IP6 or phytate): 1. Inhibits induced calcification in cultured aortic valve interstitial cells (VIC) as an in vitro model of aortic valve stenosis and 2. Whether inhibition is different in VIC obtained from healthy and calcified aortic valves. VIC from healthy (n = 5) and calcified (n = 7) human aortic valves were seeded in basic growth medium, osteogenic differentiation medium alone, or in osteogenic medium with SNF472 (3, 10, and 30 µM) and cultivated for 3 weeks. Calcification was quantified spectrophotometrically after Alizarin Red staining. In VIC from calcified valves, a complete inhibition of calcification was observed with SNF472 concentrations of 10 and 30 µM (p < .01), significantly stronger than in VIC from healthy valves. When SNF472 was added to VIC after 1 week in osteogenic medium, 30 and 100 µM SNF472 inhibited the progression of ongoing calcification by 81 and 100% (p < .01), respectively. The same concentrations of SNF472 given after 2 weeks reduced calcification by 35 and 40% respectively (not significant). SNF472 inhibited both the formation and the progression of calcification with the strongest effect in VIC from calcified valves.

Anterior mitral leaflet curvature in the beating ovine heart: a case study using videofluoroscopic markers and subdivision surfaces.

The implantation of annuloplasty rings is a common surgical treatment targeted to re-establish mitral valve competence in patients with mitral regurgitation. It is hypothesized that annuloplasty ring implantation influences leaflet curvature, which in turn may considerably impair repair durability. This research is driven by the vision to design repair devices that optimize leaflet curvature to reduce valvular stress. In pursuit of this goal, the objective of this manuscript is to quantify leaflet curvature in ovine models with and without annuloplasty ring using in vivo animal data from videofluoroscopic marker analysis. We represent the surface of the anterior mitral leaflet based on 23 radiopaque markers using subdivision surfaces techniques. Quartic box-spline functions are applied to determine leaflet curvature on overlapping subdivision patches. We illustrate the virtual reconstruction of the leaflet surface for both interpolating and approximating algorithms. Different scalar-valued metrics are introduced to quantify leaflet curvature in the beating heart using the approximating subdivision scheme. To explore the impact of annuloplasty ring implantation, we analyze ring-induced curvature changes at characteristic instances throughout the cardiac cycle. The presented results demonstrate that the fully automated subdivision surface procedure can successfully reconstruct a smooth representation of the anterior mitral valve from a limited number of markers at a high temporal resolution of approximately 60 frames per minute.

How accurate is visual assessment of synchronicity in myocardial motion? An In vitro study with computer-simulated regional delay in myocardial motion: clinical implications for rest and stress echocardiography studies.

Asynchronicity in echocardiographic images is normally assessed visually. No prior quantitative studies have determined the limitations of this approach. To quantify visual recognition of myocardial asynchronicity in echocardiographic images, computer-simulated delay phantom loops were generated from a 3.3 MHz digital image data from a normal left ventricular short-axis heart cycle acquired at 55 frames per second. Six expert observers visually assessed 30 abnormal and 3 normal loops with differing computer-induced delay patterns on 3 occasions and in this optimally simulated environment could recognize only single delays of 89 ms or more. This was improved to 71 ms or more by use of side-by-side (normal versus abnormal) comparative review. Thus visual assessment of clinically important regional delay in rest or stress echo images is limited.

Anatomic M-mode echocardiography: A new approach to assess regional myocardial function--A comparative in vivo and in vitro study of both fundamental and second harmonic imaging modes.

OBJECTIVE: To evaluate the accuracy of anatomic M-mode echocardiography (AMM). METHODS: Eight phantoms were rotated on a device at different insonation depths (IDs) in a water beaker. They were insonated with different transducer frequencies in fundamental imaging (FI) and second harmonic imaging (SHI), and the diameters were assessed with conventional M-mode echocardiography (CMM) and AMM with the applied angle correction (AC) after rotation. In addition, left ventricular wall dimensions were measured with CMM and AMM in FI and SHI in 10 volunteers. RESULTS: AC had the greatest effect on the measurement error in AMM followed by ID (AC: R2 = 0. 295, ID: R2 = 0.268; P <.0001). SHI improved the accuracy, and a difference no longer existed between CMM and AMM with an AC up to 60 degrees. In vivo the limit of agreement between AMM and CMM was -1.7 to +1.8 mm in SHI. CONCLUSION: Within its limitations (AC < 60 degrees; ID < 20 cm), AMM could be a robust tool in clinical practice.