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Fluid shear stress is intimately linked with the biological activities of vascular cells. A flexible microelectromechanical system (MEMS) sensor was developed to assess spatial- and temporal-varying components of intravascular shear stress (ISS) in the abdominal aorta of adult New Zealand white (NZW) rabbits. Real-time ISS ([ISS.sub.real-time]) was analyzed in comparison with computational fluid dynamics (CFD) simulations for wall shear stress (WSS). Three-dimensional abdominal arterial geometry and mesh were created using the GAMBIT software. Simulation of arterial flow profiles was established by FLUENT. The Navier-Stokes equations were solved for non-Newtonian blood flow. The coaxial-wire-based MEMS sensor was deployed into the abdominal arteries of rabbits via a femoral artery cutdown. Based on the CFD analysis, the entrance length of the sensor on the coaxial wire (0.4 mm in diameter) was less than 10 mm. Three-dimensional fluoroscope and contrast dye allowed for visualization of the positions of the sensor and ratios of vessel to coaxial wire diameters. Doppler ultrasound provided the velocity profiles for the CFD boundary conditions. If the coaxial wire were positioned at the center of vessel, the CFD analysis revealed a mean ISS value of 31.1 with a systolic peak at 102.8 dyn x [cm.sup.-2]. The mean WSS was computed to be 10.1 dyn x [cm.sup.-2] with a systolic peak at 33.2 dyn x [cm.sup.-2], and the introduction of coaxial wire increased the mean WSS by 5.4 dyn x [cm.sup.-2] and systolic peak by 18.0 dyn x [cm.sup.-2]. Experimentally, the mean ISS was 11.9 dyn x [cm.sup.-2] with a systolic peak at 47.0 dyn x [cm.sup.-2]. The waveform of experimental ISS was similar to that of CFD solution with a 30.2 % difference in mean and 8.9 % in peak systolic shear stress. Despite the difference between CD and experimental results, the flexible coaxial-wire-based MEMS sensors provided a possibility to assess real-time ISS in the abdominal aorta of NZW rabbits. Index Terms--Computational fluid dynamics (CFD), intravascular shear stress (ISS), microelectromechanical system (MEMS) sensors.

Hemodynamic forces, specifically fluid shear stress, play an important role in the focal nature of arterial plaque formation known as atherosclerosis. We hereby developed biocompatible and flexible intravascular microelectromechanical systems sensor to measure real-time shear stress in the aortas of New Zealand White (NZW) rabbits. Titanium (Ti) and platinum (Pt) were deposited on silicon wafers and patterned to form the sensing elements. The polymer, parylene C, provided insulation to the electrode leads and flexibility to the sensors. Based on heat transfer principle, the heat dissipation from the sensors to the blood flow altered the resistance of the sensing elements, from which shear stress was calibrated. The resistance of the sensing element was measured at approximately 1.0 k[OMEGA], and the temperature coefficient of resistance was at approximately 0.16%/[degrees]C. The individual sensors were packaged to the catheter for intravascular deployment in the aortas of NZW rabbits (n = 5). The sensor was capable of resolving spatial-and time-varying components of shear stress in the abdominal aorta. Computational fluid dynamic code based on non-Newtonian fluid properties showed comparable results within an acceptable range of experimental errors ([+ or -]9%) for the maximal and minimal values in shear stress during one cardiac cycle. Therefore, we demonstrated the capability of biocompatible sensors for real-time shear stress measurement in vivo with a potential to advance the understanding between the blood flow and vascular disease. [2007-0291] Index Terms--Microelectromechanical systems (MEMS) sensors, polymer, rabbit arterial circulation, shear stress.

Fluid shear stress modulates vascular production of endothelial superoxide anion ([[O.sub.2].sup.-]) and nitric oxide (NO). Whether the characteristics of shear stress influence the spatial variations in mitochondrial manganese superoxide dismutase (Mn-SOD) expression in vasculatures is not well defined. We constructed a three-dimensional computational fluid dynamics model simulating spatial variations in shear stress at the arterial bifurcation. In parallel, explants of arterial bifurcations were sectioned from the human left main coronary bifurcation and right coronary arteries for immunohistolocalization of Mn-SOD expression. We demonstrated that Mn-SOD staining was prominent in the pulsatile shear stress (PSS)-exposed and atheroprotective regions, but it was nearly absent in the oscillatory shear stress (OSS)-exposed regions and lateral wall of arterial bifurcation. In cultured bovine aortic endothelial cells, PSS at mean shear stress ([[tau].sub.ave]) of 23 dyn/[cm.sup.2] upregulated Mn-SOD mRNA expression at a higher level than did OSS at [[tau].sub.ave] = 0.02 dyn/[cm.sup.2] [+ or -] 3.0 dyn x [cm.sup.-2] x [s.sup.-1] and at 1 Hz (PSS by 11.3 [+ or -] 0.4-fold vs. OSS by 5.0 [+ or -] 0.5-fold vs. static condition; P < 0.05, n = 4). By liquid chromatography and tandem mass spectrometry, it was found that PSS decreased the extent of low-density lipoprotein (LDL) nitration, whereas OSS increased nitration (P < 0.05, n = 4). In the presence of LDL, treatment with Mn-SOD small interfering RNA increased intracellular nitrotyrosine level (P < 0.5, n = 4), a fingerprint for nitrotyrosine formation. Our findings indicate that shear stress in the atheroprone versus atheroprotective regions regulates spatial variations in mitochondrial Mn-SOD expression with an implication for modulating LDL nitration. superoxide dismutase; superoxide anion; nitric oxide; nitrotyrosine; low-density lipoprotein

Abstract: Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherosclerosis. Shear stress induces vascular oxidative stress via the activation of membrane‐bound NADPH oxidases present in vascular smooth muscle cells, fibroblasts, and phagocytic mononuclear cells. Shear stress acting on the endothelial cells at arterial bifurcations or branching points regulates both NADPH oxidase and nitric oxide (NO) synthase activities. The former is considered a major source of oxygen‐centered radicals (i.e., superoxide anion []) that give rise to oxidative stress; the latter is a source of nitrogen‐centered radicals (i.e., nitric oxide [NO]) that give rise to nitrative/nitrosative stress. In addition to conventional biochemical analyses, the emerging microelectromechanical systems (MEMS) provide spatial and temporal resolutions to investigate the mechanisms whereby the characteristics of shear stress regulate the biological activities of endothelial cells at the complicated arterial geometry. In parallel, the development of MEMS liquid chromatography (LC) provides a new venue to measure circulating oxidized low‐density lipoprotein (ox‐LDL) particles as a lab‐on‐a chip platform. Nanowire‐based field effect transistors further pave the way for a high throughput approach to analyze the LDL redox state. Integration of MEMS with oxidative biology is synergistic in assessing vascular oxidative stress. The MEMS LC provides an emerging lab‐on‐a‐chip platform for ox‐LDL analysis. In this context, this chapter has integrated expertise from the fields of vascular biology and oxidative biology to address the dynamics of inflammatory responses. [Copyright &y& Elsevier]

Objective: Clinical studies have demonstrated excellent hemodynamic performance of rapid deployment aortic valves; however, few studies have directly compared the performance of these valves with conventional bioprosthetic valves. Thus, the hemodynamic function of the EDWARDS INTUITY valve (rapid deployment valve) was compared with the Edwards Magna Ease valve in vitro (Edwards Lifesciences Corp, Irvine, CA USA)., Methods: Elastomeric material was used to create an aortic root model that included a left ventricular outflow tract and aortic annulus. The model was based on reconstructions from 3-dimensional multislice computed tomography images in patients with aortic stenosis; the aortic root was scaled to a 21-mm effective annulus diameter. EDWARDS INTUITY valves (21-mm diameter) were deployed by stent frame expansion within the aortic root; Edwards Magna Ease valves (21-mm diameter) were sutured to the annulus. The left ventricular outflow tract area index (left ventricular outflow tract area/baseline area) and ellipticity or noncircularity as indexed by Dmax/Dmin were measured under a video microscope after valve placement. Hemodynamic data were collected under pulsatile flow with saline (70 beats per minute, 5 L/min, 100 mm Hg aortic pressure)., Results: Compared with the Edwards Magna Ease valve (n = 4), the EDWARDS INTUITY valve (n = 4) had a greater effective orifice area (1.56 ± 0.01 vs 1.85 ± 0.06 cm, P < 0.001) and a lower transvalvular pressure gradient (23.4 ± 0.51 vs 16.8 ± 1.3 mm Hg, P < 0.001). Multiple regression analysis showed that 93% of the variation in the effective orifice area and transvalvular pressure gradient was due to variation in the left ventricular outflow tract area index and ellipticity index., Conclusions: A clinically relevant aortic root model was developed to evaluate aortic valve performance. The superior performance of the EDWARDS INTUITY valve seemed to be related to both a greater inflow area and a more circular left ventricular outflow tract.

Fluid shear stress is intimately involved in vascular oxidative stress and atherosclerosis. Oxidative stress induces molecular signaling that regulates the development of vascular calcification. The explants of New Zealand White (NZW) rabbit aortas were used to assess vascular oxidative stress in non-obstructive, albeit inflammatory, lesions. The development of Micro-Electro-Mechanical Systems (MEMS) shear stress and oxidative stress sensors has provided a means to study atherogenic hemodynamics and vascular oxidative stress. Computational fluid dynamics and Doppler ultrasound were utilized in combination with the immunohistochemistry staining to show that the flow disturbance as assessed by the micro-scale sensors in non-obstructive plaques was associated with oxidative stress relevant for initiation of the arterial plaque. Our findings represent a concerted effort to assess the relationship between oxidative stress and the mechanically unstable plaque in the presence of vascular calcification.

Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherosclerosis. Shear stress induces vascular oxidative stress via the activation of membrane-bound NADPH oxidases present in vascular smooth muscle cells, fibroblasts, and phagocytic mononuclear cells. Shear stress acting on the endothelial cells at arterial bifurcations or branching points regulates both NADPH oxidase and nitric oxide (NO) synthase activities. The former is considered a major source of oxygen-centered radicals (i.e., superoxide anion [O2(.-)]) that give rise to oxidative stress; the latter is a source of nitrogen-centered radicals (i.e., nitric oxide [NO]) that give rise to nitrative/nitrosative stress. In addition to conventional biochemical analyses, the emerging microelectromechanical systems (MEMS) provide spatial and temporal resolutions to investigate the mechanisms whereby the characteristics of shear stress regulate the biological activities of endothelial cells at the complicated arterial geometry. In parallel, the development of MEMS liquid chromatography (LC) provides a new venue to measure circulating oxidized low-density lipoprotein (ox-LDL) particles as a lab-on-a chip platform. Nanowire-based field effect transistors further pave the way for a high throughput approach to analyze the LDL redox state. Integration of MEMS with oxidative biology is synergistic in assessing vascular oxidative stress. The MEMS LC provides an emerging lab-on-a-chip platform for ox-LDL analysis. In this context, this chapter has integrated expertise from the fields of vascular biology and oxidative biology to address the dynamics of inflammatory responses.