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

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

A Role for the Cytoskeleton in Heart Looping

Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown. It is becoming clear from our experiments and those of others that left-right differences in cell proliferation in the second heart field (anterior heart field) drives the dextral direction. Evidence is accumulating that the cytoskeleton is at the center of laterality, and the bending and rotational forces associated with heart looping. If laterality pathways are modulated upstream, the cytoskeleton, including nonmuscle myosin II (NMHC-II), is altered downstream within the cardiomyocytes, leading to looping abnormalities. The cytoskeleton is associated with important mechanosensing and signaling pathways in cell biology and development. The initiation of blood flow during the looping period and the inherent stresses associated with increasing volumes of blood flowing into the heart may help to potentiate the process. In recent years, the steps involved in this central and complex process of heart development that is the basis of numerous congenital heart defects are being unraveled

A Role for the Cytoskeleton in Heart Looping

Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown. It is becoming clear from our experiments and those of others that left-right differences in cell proliferation in the second heart field (anterior heart field) drives the dextral direction. Evidence is accumulating that the cytoskeleton is at the center of laterality, and the bending and rotational forces associated with heart looping. If laterality pathways are modulated upstream, the cytoskeleton, including nonmuscle myosin II (NMHC-II), is altered downstream within the cardiomyocytes, leading to looping abnormalities. The cytoskeleton is associated with important mechanosensing and signaling pathways in cell biology and development. The initiation of blood flow during the looping period and the inherent stresses associated with increasing volumes of blood flowing into the heart may help to potentiate the process. In recent years, the steps involved in this central and complex process of heart development that is the basis of numerous congenital heart defects are being unraveled

Ultrasound enhancement of drug release across non-ionic surfactant membranes

A method of targeted drug delivery and imaging using nonionic surfactant vesicles (niosomes) in combination with ultrasound is presented. Niosomes have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. The niosomes may be administered to the subject via catheter. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique and used for encapsulation studies. Carboxyfluorescein dye (CF) was used as a drug model to demonstrate delivery. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound was monitored. It was found that ultrasound at specific frequencies can reversibly permeabilize the lipid membrane of niosomes to allow the controlled release of a compound without destroying the niosome structure

Ultrasound enhancement of drug release across non-ionic surfactant membranes

A method of targeted drug delivery and imaging using nonionic surfactant vesicles (niosomes) in combination with ultrasound. Niosomes have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique and used for encapsulation studies. Carboxyfluorescein dye (CF) was used as a drug model to demonstrate delivery. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound was monitored. Dye concentration in niosome samples decreased while the population and size distribution of the niosome remained largely unchanged. Ultrasound is demonstrated to enhance the rate of dye diffusion across the niosome membrane non-destructively