Incorporation of myofilament activation mechanics into a lumped model of the human heart.

The success and usefulness of lumped cardiovascular models are directly dependent on the physiological fidelity of their formulation. In most existing lumped formulations for the heart, the compliance of the chamber is modeled based on its electrical analog, the capacitor. This has traditionally resulted in the use of a pre-described time-varying stiffness modulus for simulating the cardiac contractions. Unfortunately, such a time-varying stiffness does not include any physiological contractile machinery and thus no dependency on fiber sarcomere length and intracellular calcium concentrations, key mechanisms responsible for proper cardiac function. In this paper a lumped cardiovascular model is presented that is based on the incorporation of detailed myofilament activation for simulating the ventricular calcium binding and cross-bridging mechanism. Upon validation against experimental data, it is shown that the new myofilament activation-based model considerably increases the physiological validity and internal consistency of the cardiovascular simulations in comparison to the traditional variable compliance-based models. It is also shown, through specific case studies, that the present model can serve as a quick response tool for testing various hypotheses concerning the impact of the calcium binding and crossbridge kinetics on the overall performance of the cardiovascular system.

Enhanced ventricular untwisting during exercise: a mechanistic manifestation of elastic recoil described by Doppler tissue imaging.

BACKGROUND: The cascade of events by which early diastolic left ventricular (LV) filling increases with exercise is not fully elucidated. Doppler tissue imaging (DTI) can detect myocardial motion, including torsion, whereas color M-mode Doppler (CMM) can quantify LV intraventricular pressure gradients (IVPGs). METHODS AND RESULTS: Twenty healthy volunteers underwent echocardiographic examination with DTI at rest and during submaximal supine bicycle exercise. We assessed LV long-/short-axis function, torsion, volume, inflow dynamics, and early diastolic IVPG derived from CMM data. LV torsion and untwisting velocity increased with exercise (torsion, 11+/-4 degrees to 24+/-8 degrees ; untwisting velocity, -2.0+/-0.7 to -5.6+/-2.3 rad/s) that was associated with an increase in IVPG (1.4+/-0.5 to 3.7+/-1.2 mm Hg). Untwisting in normal subjects occurred during isovolumic relaxation and early filling, significantly before long-axis lengthening or radial expansion. The clinical feasibility of this method was tested in 7 patients with hypertrophic cardiomyopathy (HCM); torsion was higher at rest but did not increase with exercise (16+/-4 degrees to 14+/-6 degrees), whereas untwisting was delayed and unenhanced (-1.6+/-0.8 to -2.3+/-1.2 rad/s). In concert, IVPG was similar at rest (1.2+/-0.3 mm Hg), but the exercise response was blunted (1.6+/-0.8 mm Hg). In normal subjects and HCM patients, there was a similar linear relation between IVPG and untwisting rate, with an overall correlation coefficient of r=0.75 (P<0.0001). CONCLUSIONS: LV untwisting appears to be linked temporally with early diastolic base-to-apex pressure gradients, enhanced by exercise, which may assist efficient LV filling, an effect that appears blunted in HCM. Thus, LV torsion and subsequent rapid untwisting appear to be manifestations of elastic recoil, critically linking systolic contraction to diastolic filling.

Maturational and adaptive modulation of left ventricular torsional biomechanics: Doppler tissue imaging observation from infancy to adulthood.

BACKGROUND: Left ventricular (LV) torsional deformation, based in part on the helical myocardial fiber architecture, is an important component of LV systolic and diastolic performance. However, there is no comprehensive study describing its normal development during childhood and adult life. METHODS AND RESULTS: Forty-five normal subjects (25 children and 20 adults; aged 9 days to 49 years; divided into 5 groups: infants, children, adolescents, and young and middle-age adults) underwent assessment of LV torsion and untwisting rate by Doppler tissue imaging. LV torsion increased with age, primarily owing to augmentation in basal clockwise rotation during childhood and apical counterclockwise rotation during adulthood. Although LV torsion and untwisting overall showed age-related increases, when normalized by LV length, they showed higher values in infancy and middle age. The proportion of untwisting during isovolumic relaxation was lowest in infancy, increased during childhood, and leveled off thereafter, whereas peak untwisting performance (peak untwisting velocity normalized by peak LV torsion) showed a decrease during adulthood. CONCLUSIONS: We have shown the maturational process of LV torsion in normal subjects. Net LV torsion increases gradually from infancy to adulthood, but the determinants of this were different in the 2 age groups. The smaller LV isovolumic untwisting recoil during infancy and its decline in adulthood may suggest mechanisms for alterations in diastolic function.

Fluid-structural dynamics of ground-based and microgravity caloric tests.

Microgravity caloric tests aboard the 1983 SpaceLab1 mission produced nystagmus results with an intensity comparable to those elicited during post- and pre- flight tests, thus contradicting the basic premise of Barany's convection hypothesis for caloric stimulation. In this work, we present a dynamic fluid structural analysis of the caloric stimulation of the lateral semicircular canal based on two simultaneous driving forces for the endolymphatic flow: natural convection driven by the temperature-dependent density variation in the bulk fluid and expansive convection caused by direct volumetric displacement of the endolymph during the thermal irrigation. Direct numerical simulations indicate that on earth, the natural convection mechanism is dominant. But in the microgravity environment of orbiting spacecraft, where buoyancy effects are mitigated, expansive convection becomes the sole mechanism for producing cupular displacement. A series of transient 1 g and microgravity case studies are presented to delineate the differences between the dynamics of the 1 g and microgravity endolymphatic flows. The impact of these different flow dynamics on the endolymph-cupula fluid-structural interactions is also analyzed based on the time evolutions of cupular displacement and velocity and the transcupular pressure differences.

Echocardiographic assessment of regional ventricular function after device-based change of left ventricular shape.

We assessed the effects of implantation of Myosplint (Myocor, Maple Grove, Minn), a device that changes left ventricular (LV) cross-sectional shape from circular to bilobar, on regional LV function. A total of 10 open-chest dogs with tachycardia-induced cardiomyopathy were studied before and after Myosplint implantation. LV cross-sectional epicardial echocardiography at the papillary muscle level was performed along with acquisition of hemodynamic data. LV normalized thickening, fractional thickening, end-diastolic thickness, and end-diastolic curvatures were calculated for 10 LV segments. Myosplint implantation did not affect LV hemodynamics, but decreased average end-diastolic curvature (P <.0001) and increased its segmental heterogeneity (P <.0001). There was no change in average fractional thickening, whereas normalized thickening increased (P =.05). In contrast, segmental heterogeneity of both normalized and fractional thickening increased (P =.02 and P =.01, respectively). Structural modeling confirmed that Myosplint implantation increases regional stress heterogeneity and curvature heterogeneity. LV cross-sectional shape markedly affects regional LV performance.

Influence of structural geometry on the severity of bicuspid aortic stenosis.

Doppler-derived gradients may overestimate total pressure loss in degenerative and prosthetic aortic valve stenosis (AS) due to unaccounted pressure recovery distal to the orifice. However, in congenitally bicuspid valves, jet eccentricity may result in a higher anatomic-to-effective orifice contraction ratio, resulting in an increased pressure loss at the valve and a reduced pressure recovery distal to the orifice leading to greater functional severity. The objective of our study was to determine the impact of local geometry on the total versus Doppler-derived pressure loss and therefore the assessed severity of the stenosis in bicuspid valves. On the basis of clinically obtained measurements, two- and three-dimensional computer simulations were created with various local geometries by altering the diameters of the left ventricular outflow tract (LVOT; 1.8-3.0 cm), orifice diameter (OD; 0.8-1.6 cm), and aortic root diameter (AR; 3.0-5.4 cm). Jet eccentricity was altered in the models from 0 to 25 degrees. Simulations were performed under steady-flow conditions. Axisymmetric simulations indicate that the overall differences in pressure recovery were minor for variations in LVOT diameter (<3%). However, both OD and AR had a significant impact on pressure recovery (6-20%), with greatest recovery being the larger OD and the smaller recovery being the AR. In addition, three-dimensional data illustrate a greater pressure loss for eccentric jets with the same orifice area, thus increasing functional severity. In conclusion, jet eccentricity results in greater pressure loss in bicuspid valve AS due to reduced effective orifice area. Functional severity may also be enhanced by larger aortic roots, commonly occurring in these patients, leading to reduced pressure recovery. Thus, for the same anatomic orifice area, functional severity is greater in bicuspid than in degenerative tricuspid AS.

Effect of gravity on the caloric stimulation of the inner ear.

Robert Barany won the 1914 Nobel Prize in medicine for his convection hypothesis for caloric stimulation. Microgravity caloric tests aboard the 1983 SpaceLab 1 mission produced nystagmus results that contradicted the basic premise of Barany's convection theory. In this paper, we present a fluid structural analysis of the caloric stimulation of the lateral semicircular canal. Direct numerical simulations indicate that on earth, natural convection is the dominant mechanism for endolymphatic flow. However, in the microgravity environment of orbiting spacecraft, where buoyancy effects are mitigated, an expansive convection becomes the sole mechanism for producing endolymph motion and cupular displacement. Transient 1 g and microgravity case studies are presented to delineate the different dynamic behaviors of the 1 g and microgravity endolymphatic flows. The associated fluid-structural interactions are also analyzed based on the time evolution of cupular displacements.

A new automated method for the quantification of mitral regurgitant volume and dynamic regurgitant orifice area based on a normalized centerline velocity distribution using color M-mode and continuous wave Doppler imaging.

Previous echocardiographic techniques for quantifying valvular regurgitation (PISA) are limited by factors including uncertainties in orifice location and hemispheric convergence assumption. Using computational fluid dynamics simulations, we developed a new model for the estimation of orifice diameter and regurgitant volume without the aforementioned assumptions of the PISA technique. Using experimental data obtained from the in vitro flow model we successfully validated our new model. The model output (y) and reference (x) values were in close agreement (y = 0.95x + 0.38, r = 0.96, error = 1.68 +/- 7.54% for the orifice diameter and y = 1.18x - 4.72, r = 0.93, error = 6.48 +/- 16.81% for the regurgitant volume).