970–6 In Vivo Studies of Aortic Stenosis: Role of Inertial and Viscous Forces in Doppler/Catheter Discrepancies

In previous studies in vitro we have used a Reynolds number approach to analyze second order effects on pressure recovery distal to stenosis. It was shown that two fundamentally different effects, viscous losses and turbulent dissipation, can control the basic overestimation due to pressure recovery at both ends of the Reynolds number scale. Having quantified this effect in vitro, this study attempted to reconcile Doppler and catheter gradients across aortic stenosis in vivo.MethodsIn 4 sheep with surgically created aortic stenosis, 30 hemodynamic states were studied (4–11 per sheep) using Millar transducers in the LV and Aorta (peak PG ranged 3–150mmHg). A Vingmed 775 interfaced to a computer was used to measure CVV velocities simultaneously with catheter recordings.ResultsInstantaneous Doppler peak gradient correlated with catheter instantaneous gradient throughout the range of baseline and stenotic conditions (r=0.973, SEE=8.7mmHg). but Doppler overestimated cath gradient (up to 70%) for all stenotic valve conditions by an average of 17%. Plotting overestimation versus Reynolds number revealed a second order profile of the shape derived in vitro. Correction of Doppler gradients using this parabolic factor reduced average overestimation from 17% to 1.5%.ConclusionsOverestimation due to pressure recovery is basic to aortic stenosis, but this overestimation can be partially canceled by two apparently unrelated effects: viscous effects and turbulent dissipation. The former is deleted from the simplified Bernoulli equation, but more importantly, the latter is not characterized by any form of the Bernoulli equation. A Reynolds number based approach characterizes the relative importance of these effects and could lead to reconciliation of Doppler and catheter gradients in the clinical setting

774-5 Effect of Cardiac Translation on Measurement of Left Ventricular Wall Velocities: Implications for Doppler Imaging of Myocardium

Doppler imaging of the myocardium is a new application which has the potential to record myocardial velocities. These recorded velocities, however, include cardiac motion independent of ventricular contraction. A measured myocardial velocity, therefore, represents the net vector of contraction, translation, and rotation. To determine the effects of cardiac translation on myocardial velocities, 2-dimensional (2D) and M-mode echocardiographic recordings were obtained in 10 normal subjects. The average anteroseptal (AS) and posterior wall (PW) velocities were measured by 2D echo directed M-mode in the centerline of the parasternal short-axis view. Translation was measured from 2D echo cine-loop display as the displacement of the epicardial junction of the right ventricular free wall and interventricular septum during systole. The average translational velocity is reported as the component of the displacement vector parallel to the M-mode beam (+=toward transducer). The AS and PW velocities (cm/sec) displayed in the table represent net measured velocities, which include the translational vector.ResultsASPWTranslationMean±SD3.2±0.54.5±1.1+1.3±0.6Range2.4 to 4.03.4 to 6.9-l.4 to+2.4In 8/10 subjects the velocity vector was positive. The mean percent error in the M-mode derived velocities due to translation was 41% for the AS wall and 31% for the PW.Conclusions1) As measured by 2D echocardiography, the magnitude of the translational vector is significant when compared to the M-mode derived myocardial velocities. 2) The relative error demonstrated in the measured velocities may be further modified when applied in two dimensions, due to the angle of incidence of the Doppler beam. 3) New techniques for measuring myocardial velocities, such as Doppler imaging of the myocardium, should incorporate algorithms which correct for the translational vector

Abnormalities of the Left Ventricular Outflow Tract Associated With Discrete Subaortic Stenosis in Children: An Echocardiographic Study

AbstractObjectives. The purpose of this study was to examine the echocardiographic abnormalities of the left ventricular outflow tract associated with subaortic stenosis in children.Background. Considerable evidence suggests that subaortic stenosis is an acquired and progressive lesion, but the etiology remains unknown. We have proposed a four-stage etiologic process for the development of subaortic stenosis. This report addresses the first stage by defining the morphologic abnormalities of the left ventricular outflow tract present in patients who develop subaortic stenosis.Methods. Two study groups were evaluated—33 patients with isolated subaortic stenosis and 12 patients with perimembranous ventricular septal defect and subaortic stenosis—and were compared with a size- and lesion-matched control group. Subjects ranged in age from 0.05 to 23 years, and body surface area ranged from 0.17 to 2.3 m2. Two independent observers measured aortoseptal angle, aortic annulus diameter and mitral-aortic separation from previously recorded echocardiographic studies.Results. The aortoseptal angle was steeper in patients with isolated subaortic stenosis than in control subjects (p < 0.001). This pattern was also true for patients with ventricular septal defect and subaortic stenosis compared with control subjects (p < 0.001). Neither age nor body surface area was correlated with aortoseptal angle. A trend toward smaller aortic annulus diameter indexed to patient size was seen between patients and control subjects but failed to achieve statistical significance (p = 0.08). There was an excellent interrater correlation in aortoseptal angle and aortic annulus measurement. The mitral-aortic separation measurement was unreliable. Our results, specifically relating steep aortoseptal angle to subaortic stenosis, confirm the results of other investigators.Conclusions. This study demonstrates that subaortic stenosis is associated with a steepened aortoseptal angle, as defined by two-dimensional echocardiography, and this association holds in patients with and without a ventricular septal defect. A steepened aortoseptal angle may be a risk factor for the development of subaortic stenosis.(J Am Coll Cardiol 1997;30:255–9

Clinical application of three-dimensional echocardiographic laser stereolithography: Effect of leaflet funnel geometry on the coefficient of orifice contraction, pressure loss and the Gorlin formula in aortic stenosis

International audienc

Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids

Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer® (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), α1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions

1020-4 Proximal Isovelocity Surface Area Method Applied to Non-Planar Surfaces: Implications of In Vitro Studies for Clinical Regurgitation and Stenosis

The color Doppler proximal isavelocity surface area (PISA) method accurately estimates volume flow rate (Q) across a planar surface in vitro. This method has been applied clinically to estimating valvular regurgitant flow using a hemispherical formula requiring measurement of a single axial radius. However, since cardiac valves may approximate convex shape, the most accurate PISA formula for calculating Q across a valve should be different from that for a planar model. We evaluated variations of PISA formula in a planar model and two convex-shaped models.MethodsThree circular orifice diameters (Ø=5.2, 8, 12mm) on hemispherical bails (diameter, D=38 and 58mm) and one planar model were studied in a constant flow system (Fig. 1). The radii (A and B) of PISA were measured in axial and transverse views. Flow velocity and actual Q across orifices were varied from 0.3–7.7m/s and 0.9–8.6 l/min, respectively.Results1) B/A ratios were dependent on actual Q and orifice sizes. 2) B/A ratios were significantly larger for convex models than for a planar model at actual Q below 5 l/min (p&lt;0.001) (Fig.2 shows data for orifice Ø=8 mm at aliasing velocity between 15 and 30 cm/s). 3) In a convex model (D=38 mm), B/A ratios for orifices Ø=5.2,8,12mm at actual Q=1.5 l/min were 1.35±0.07, 1.62±0.07 and 1.85±0.08, respectively (p&lt;0.001). The D=58mm convex model demonstrated similar results.ConclusionThe shape of PISA for a convex surface is less hemispherical than for a planar surface. Decreased axial radius is partially compensated for by increased transverse radius. Since precise orifice geometry is often unknown clinically, measurement of both PISA axial and transverse radii is important to minimize under-estimation of regurgitant or stenotic flo