Lee L. Huntsman

Determination of the stenotic aortic valve area in adults using Doppler echocardiography

The severity of aortic stenosis was evaluated by Doppler echocardiography in 48 adults (mean age 67 years) undergoing cardiac catheterization. Maximal Doppler systolic gradient correlated with peak to peak pressure gradient (r = 0.79, y = 0.63x + 25.2 mm Hg) and mean Doppler gradient correlated with mean pressure gradient (r = 0.77, y = 0.59x + 10.0 mm Hg) by manometry. The transvalvular pressure gradient is flow dependent, however, and associated left ventricular dysfunction was common in our patients (33%). Thus, of the 32 patients with an aortic valve area less than or equal to 1.0 cm2 at catheterization, 6 (19%) had a peak Doppler gradient less than 50 mm Hg. To take into account the influence of volume flow, aortic valve area was calculated as stroke volume, measured simultaneously by thermodilution, divided by the Doppler systolic velocity integral in the aortic jet. Aortic valve areas calculated by this method were compared with results at catheterization in the total group (r = 0.71). Significant aortic insufficiency was present in 71% of the population. In the subgroup without significant coexisting aortic insufficiency, closer agreement of valve area with catheterization was noted (n = 14, r = 0.91, y = 0.83x + 0.24 cm2). Transaortic stroke volume can be determined noninvasively by Doppler echocardiographic measures in the left ventricular outflow tract, just proximal to the stenotic valve. Aortic valve area can then be calculated as left ventricular outflow tract cross-sectional area times the systolic velocity integral of outflow tract flow, divided by the systolic velocity integral in the aortic jet.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcutaneous determination of aortic blood-flow velocities in man

A transcutaneous ultrasonic Doppler technique for measurement of aortic blood-flow velocities has been developed and compared to more established techniques in order to evaluate its potential usefulness. It is possible by this method to quantitate blood velocity in both the ascending aorta and the aortic arch with ease and reliability. Ultrasonic access to the aorta from the suprasternal notch proved adequate in more than 90 per cent of the normal subjects examined. If further clinical trials prove as encouraging, this technique may be of significant value for patient monitoring and cardiac diagnosis.

Cardiac Muscle Models An Overextension of Series Elasticity

Quick-stretch and quick-release experiments were performed on right ventricular cat papillary muscles to test the applicability of the Hill model to cardiac mechanics. Series elastic component (SEC) force-length curves were calculated from stretches and releases carried out at various times during the contractile cycle. At any SEC force, the SEC elastic modulus depended on the time during the contractile cycle at which it was measured. When measured at the same time and at the same SEC force, elastic moduli obtained by releases of less than 1% of muscle length differed from those obtained by corresponding stretches. Larger stretches, in fact, appeared to yield negative elastic moduli. Thus, a unique SEC modulus could not be identified at any level of SEC force. It is concluded that the concept of the SEC as a passive elasticity appears unsatisfactory and, as a consequence, that the quantitative validity of the Hill model for cardiac muscle is questionable. Moreover, since an anatomical counterpart of the SEC has not been identified, the Hill model also appears unsatisfactory from a structural point of view.

Ca2+ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle.

The influence of Ca2+ and sarcomere length on myocardial crossbridge kinetics was studied in ferret papillary muscle by measuring the rate of force redevelopment following a rapid length step that dropped the force to zero. Tetanic stimulation with 5 mumol/L ryanodine was used to obtain a steady-state contraction, and segment length was measured and controlled using a sense-coil technique that measures changes in the cross-sectional area of the central region of the muscle. The rate constant for the recovery of force (ktr) following a rapid length release was obtained by fitting the data with a single exponential function. Contrary to results from skinned skeletal fibers in which ktr increases almost 10-fold from low to maximal activation levels, ktr was found not to increase at higher activation levels in this study. Similarly, although force increased with segment length under all conditions, ktr never increased with length. Data presented here are consistent with a model of myocardial Ca2+ activation in which Ca2+ modulates the number of crossbridges interacting with the thin filament and are inconsistent with a model in which Ca2+ modulates the kinetics of transitions to force producing states within the actomyosin cycle. Differences in the activation dependence of the force redevelopment rate between cardiac and skeletal muscle suggest that there are fundamental differences in the mechanism of Ca2+ activation between these two muscle types.

UNLOADED SHORTENING OF SKINNED MUSCLE FIBERS FROM RABBIT ACTIVATED WITH AND WITHOUT CA2

Unloaded shortening velocity (VUS) was determined by the slack method and measured at both maximal and submaximal levels of activation in glycerinated fibers from rabbit psoas muscle. Graded activation was achieved by two methods. First, [Ca2+] was varied in fibers with endogenous skeletal troponin C (sTnC) and after replacement of endogenous TnC with either purified cardiac troponin C (cTnC) or sTnC. Alternatively, fibers were either partially or fully reconstituted with a modified form of cTnC (aTnC) that enables force generation and shortening in the absence of Ca2+. Uniformity of the distribution of reconstituted TnC across the fiber radius was evaluated using fluorescently labeled sTnC and laser scanning fluorescence confocal microscopy. Fiber shortening was nonlinear under all conditions tested and was characterized by an early rapid phase (VE) followed by a slower late phase (VL). In fibers with endogenous sTnC, both VE and VL varied with [Ca2+], but VE was less affected than VL. Similar results were obtained after extraction of TnC and reconstitution with either sTnC or cTnC, except for a small increase in the apparent activation dependence of VE. Partial activation with aTnC was obtained by fully extracting endogenous sTnC followed by reconstitution with a mixture of aTnC and cTnC (aTnC:cTnC molar ratio 1:8.5). At pCa 9.2, VE and VL were similar to those obtained in fibers reconstituted with sTnC or cTnC at equivalent force levels. In these fibers, which contained aTnC and cTnC, VE and VL increased with isometric force when [Ca2+] was increased from pCa 9.2 to 4.0. Fibers that contained a mixture of a TnC and cTnC were then extracted a second time to selectively remove cTnC. In fibers containing aTnC only, VE and VL were proportional to the resulting submaximal isometric force compared with maximum Ca(2+)-activated control. With aTnC alone, force, VE, and VL were not affected by changes in [Ca2+]. The similarity of activation dependence of VUS whether fibers were activated in a Ca(2+)-sensitive or -insensitive manners implies that VUS is determined by the average level of thin filament activation and that, with sTnC or cTnC, VUS is affected by Ca2+ binding to TnC only.

Models of calcium activation account for differences between skeletal and cardiac force redevelopment kinetics

To explain observed differences in the activation dependence of force redevelopment kinetics between cardiac and skeletal muscle, two numerical models of contractile regulation by Ca2+ were investigated. Ca2+ binding and force production were each modelled as two-state processes with forward and reverse rate constants taken from the literature. The first model incorporates four possible thin-filament states. In the second model Ca2+ is assumed not to dissociate from a thin-filament unit in the force-generating state, resulting in three states. The four-state model can account for the activation dependence of the rate constant of tension redevelopment (ktr) seen in skeletal muscle, without requiring that Ca2+ directly modulates the kinetics of any step in the cross-bridge cycle. Using identical kinetic parameters, the three-state model shows no activation dependence of ktr, consistent with our results in cardiac muscle. Following a step increase in [Ca2+], the rate of rise in tension (as described by the rate constant kCa) varies with the final [Ca2+] for both models, consistent with experimental results from skeletal and cardiac muscle. These numerical models demonstrate that experimental measurements thought to reveal changes in kinetic parameters may simply reflect coupling between the two kinetic processes of Ca2+ binding and force generation. Furthermore, the models present possible differences in the Ca2+ activation scheme between cardiac and skeletal muscle which can account for the contrasting activation dependencies of force redevelopment kinetics

Influence of Ca2+ on force redevelopment kinetics in skinned rat myocardium

The influence of Ca2+ on isometric force kinetics was studied in skinned rat ventricular trabeculae by measuring the kinetics of force redevelopment after a transient decrease in force. Two protocols were employed to rapidly detach cycling myosin cross-bridges: a large-amplitude muscle length ramp followed by a restretch back to the original length or a 4% segment length step. During the recovery of force, the length of the central region of the muscle was controlled by using a segment marker technique and software feedback control. Tension redevelopment was fit by a rising exponential governed by the rate constant ktr for the ramp/restretch protocol and kstep for the step protocol. ktr and kstep averaged 7.06 s-1 and 15.7 s-1, respectively, at 15 degrees C; neither ktr nor kstep increased with the level of Ca2+ activation. Similar results were found at submaximum Ca2+ levels when sarcomere length control by laser diffraction was used. The lack of activation dependence of ktr contrasts with results from fast skeletal fibers, in which ktr varies 10-fold from low to high activation levels, and suggests that Ca2+ does not modulate the kinetics of cross-bridge attachment or detachment in mammalian cardiac muscle.

On the contribution of volume currents to the total magnetic field resulting from the heart excitation process: a simulation study

Data from a simulation study of volume current contribution to the total magnetic field produced in the heart excitation process is presented. Contributions from different tissue types are analyzed and effects of torso size are studied. A high resolution finite element model of an adult male torso composed of 19 tissue types is used. It has detailed description of tissue geometries and therefore is well suited for analyzing the contribution of the primary and secondary currents to the magnetic field. The computed results show major contribution of volume currents from blood, myocardium, and lungs and less significant contribution from liver, muscle, and other tissues. The contribution to the volume currents from the blood in the ventricles was highest. These simulations suggest that contribution to the total magnetic field due to volume currents flowing in tissues other than blood could be accounted for by simply multiplying the total field values by a constant. Values of these multipliers would be based on the tissue type and time in the excitation cycle. Effects of torso size on the computed magnetic fields are also evaluated. Our data shows that a torso extending approximately 3 cm above and below the heart produces field patterns similar to a larger torso model extending from top of guts to the bottom of neck. Thus a shorter torso model would be sufficient for cardiac magnetic field analysis. These results are of interest for future modeling of magnetocardiograms and solving the inverse problem.

MCG simulations with a realistic heart-torso model

Magnetocardiograms (MCGs) simulated high-resolution heart-torso model of an adult subject were compared with measured MCGs acquired from the same individual. An exact match of the measured and simulated MCGs was not found due to the uncertainties in tissue conductivities and cardiac source positions. However, general features of the measured MCGs were reasonably represented by the simulated data for most, but not all of the channels. This suggests that the model accounts for the most important mechanisms underlying the genesis of MCGs and may be useful for cardiac magnetic field modeling under normal and diseased states. MCGs were simulated with a realistic finite-element heart-torso model constructed from segmented magnetic resonance images with 19 different tissue types identified. A finite-element model was developed from the segmented images. The model consists of 2.51 million brick-shaped elements and 2.58 million nodes, and has a voxel resolution of 1.56/spl times/1.56/spl times/3 mm. Current distributions inside the torso and the magnetic fields and MCGs at the gradiometer coil locations were computed. MCGs were measured with a Philips twin Dewar first-order gradiometer SQUID-system consisting of 31 channels in one tank and 19 channels in the other.

Calcium-independent activation of skeletal muscle fibers by a modified form of cardiac troponin C.

A conformational change accompanying Ca2+ binding to troponin C (TnC) constitutes the initial event in contractile regulation of vertebrate striated muscle. We replaced endogenous TnC in single skinned fibers from rabbit psoas muscle with a modified form of cardiac TnC (cTnC) which, unlike native cTnC, probably contains an intramolecular disulfide bond. We found that such activating TnC (aTnC) enables force generation and shortening in the absence of calcium. With aTnC, both force and shortening velocity were the same at pCa 9.2 and pCa 4.0. aTnc could not be extracted under conditions which resulted in extraction of endogenous TnC. Thus, aTnC provides a stable model for structural studies of a calcium binding protein in the active conformation as well as a useful tool for physiological studies on the primary and secondary effects of Ca2+ on the molecular kinetics of muscle contraction.