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A D McCulloch

Publications and source records attributed to A D McCulloch.

70 records · Page 4Linked to original sources
PubMed1993

Nonhomogeneous analysis of epicardial strain distributions during acute myocardial ischemia in the dog.

To study the nonuniform mechanical function that occurs in normal and ischemic ventricular myocardium, a new method has been developed and validated. An array of 25 lead markers (approximately 4 x 4 cm) was sewn onto the epicardium of the anterior free wall of the left ventricle in an open-chest, anesthetized canine preparation. Biplane cineradiography was used to track marker positions throughout the cardiac cycle before and during episodes of acute ischemia induced by occlusion of the left anterior descending coronary artery. To estimate two-dimensional nonhomogeneous deformations in the region at risk and its border zone with normally perfused tissue, surfaces defined by bicubic Hermite isoparametric finite element interpolation were fitted by least squares to the three-dimensional marker coordinates in successive cine frames. Global smoothing functions prevented ill-conditioning in areas of low marker density. Continuous distributions of systolic finite strains referred to the end-diastolic state were obtained under normal and ischemic conditions without the conventional assumption of homogeneous strain analysis. Substantial regional variations in epicardial strains were observed in both the normal and ischemic heart. The method was validated in regions of small to moderate strain variations by comparing the continuous distributions of strain components with piecewise-constant measurements made using marker triplets and homogeneous strain theory. The influence of marker density was examined by recomputing strains from surfaces fitted to subsets of the original array. Further validation of moderate to large strain variations was obtained by simulating a nonuniform distribution of stretch across a planar sheet and computing strains both analytically and using the current method. The new method allows for more comprehensive measurements of distributed ventricular function, providing a tool with which to quantify better the nonhomogeneous function associated with regional ischemia.

Animals↗
PubMed1993

Mechanics of active contraction in cardiac muscle: Part I--Constitutive relations for fiber stress that describe deactivation.

Constitutive relations for active fiber stress in cardiac muscle are proposed and parameters are found that allow these relations to fit experimental data from the literature, including the tension redeveloped following rapid deactivating length perturbations. Contraction is driven by a length-independent free calcium transient. The number of actin sites available to react with myosin is determined from the total number of actin sites (available and inhibited), free calcium and the length history-dependent association and dissociation rates of two Ca2+ ions and troponin as governed by a first-order, classical kinetics, differential equation. Finally, the relationship between active tension and the number of available actin sites is described by a general cross-bridge model. Bridges attach in a single configuration at a constant rate, the force within each cross-bridge varies linearly with position, and the rate constant of bridge detachment depends both on position and time after onset of contraction. In Part II, these constitutive relations for active stress are incorporated in a continuum mechanics model of the left ventricle that predicted end-systolic transmural strain distributions as observed experimentally.

Actins↗
PubMed1993

Mechanics of active contraction in cardiac muscle: Part II--Cylindrical models of the systolic left ventricle.

Models of contracting ventricular myocardium were used to study the effects of different assumptions concerning active tension development on the distributions of stress and strain in the equatorial region of the intact left ventricle during systole. Three models of cardiac muscle contraction were incorporated in a cylindrical model for passive left ventricular mechanics developed previously [Guccione et al. ASME Journal of Biomechanical Engineering, Vol. 113, pp. 42-55 (1991)]. Systolic sarcomere length and fiber stresses predicted by a general "deactivation" model of cardiac contraction [Guccione and McCulloch, ASME Journal of Biomechanical Engineering, Vol. 115, pp. 72-81 (1993)] were compared with those computed using two less complex models of active fiber stress: In a time-varying "elastance" model, isometric tension development was computed from a function of peak intracellular calcium concentration, time after contraction onset and sarcomere length; a "Hill" model was formulated by scaling this isometric tension using the force-velocity relation derived from the deactivation model. For the same calcium ion concentration, the sarcomeres in the deactivation model shortened approximately 0.1 microns less throughout the wall at end-systole than those in the other models. Thus, muscle fibers in the intact ventricle are subjected to rapid length changes that cause deactivation during the ejection phase of a normal cardiac cycle. The deactivation model predicted rather uniform transmural profiles of fiber stress and cross-fiber stress distributions that were almost identical to those of the radial component. These three components were indistinguishable from the principal stresses. Transmural strain distributions predicted at end-systole by the deactivation model agreed closely with experimental measurements from the anterior free wall of the canine left ventricle.

Animals↗
PubMed1993

Nonhomogeneous ventricular wall strain: analysis of errors and accuracy.

Nonhomogeneous distributions of strains are simulated and utilized to determine two potential errors in the measurement of cardiac strains. First, the error associated with the use of single-plane imaging of myocardial markers is examined. We found that this error ranges from small to large values depending on the assumed variation in stretch. If variations in stretch are not accompanied by substantial regional changes in ventricular radius, the associated error tends to be quite small. However, if the nonuniform stretch field is a result of substantial variations in local curvature from their reference values, large errors in stretch and strain occur. For canine hearts with circumferential radii of 2 to 4 cm, these errors in stretch may be as great as 30 percent or more. Moreover, gradients in stretch may be over- or underestimated by as much as 100 percent. In the second part of this analysis, the influence of random measurement errors in the coordinate positions of markers on strains computed from them is studied. Arrays of markers covering about 16 cm2 of ventricular epicardium are assumed and nonuniform stretches imposed. The reference and deformed positions of the markers are perturbed with Gaussian noise with a standard deviation of 0.1 mm, and then strains are computed using either homogeneous strain theory or a nonhomogeneous finite element method. For the strain distributions prescribed, it is found that the finite element method reduces the error resulting from noise by about 50 percent over most of the region. Accurate measurements of cardiac strain distributions are needed for correlation with and validation of realistic three-dimensional stress analyses of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of residual stress on transmural sarcomere length distributions in rat left ventricle.

It has been previously shown that the myocardium in the walls of the unloaded passive left ventricle (LV) is not stress free. To assess the functional significance of residual stress in the ventricular wall, we compared the transmural distributions of sarcomere length (SL) in specimens of rat LV myocardium fixed in the unloaded (residually stressed) and stress-free states. When a cross-sectional ring cut from the equatorial region of the freshly arrested rat hearts was cut radially to relieve residual stress, it sprang open into an arc with a mean opening angle of 45 +/- 15 degrees (SD) (n = 8). During immersion fixation in glutaraldehyde, the opening angle increased 9.3 +/- 7.1 degrees (SD) overall. SLs were measured at 16 equally spaced transmural locations from the free wall in the stress-free tissue sections and were compared with control measurements from adjacent cross-sectional rings in which residual stress had not been relieved. Average SL for the stress-free tissue (n = 11) was 1.84 +/- 0.05 (SD) microns and for the unloaded tissue was 1.83 +/- 0.06 (SD) microns. However, analysis of covariance on the pooled data showed that the transmural distributions were significantly different (P < 0.0001). Whereas SL was uniform across the wall in the stress-free state with a mean gradient of -0.014 +/- 0.044 (SD) microns/total wall thickness, there was a significant decrease (P = 0.001) in SL from epicardium to endocardium in the intact unloaded tissue [slope = -0.114 +/- 0.054 (SD) microns/total wall thickness].(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Mechanical effects of coronary perfusion in the passive canine left ventricle.

Mechanical effects of coronary perfusion on passive left ventricular filling were studied in seven isolated potassium-arrested dog hearts subjected to static pressure loading. With the use of a biplane video method, midanterior epicardial deformations were measured before, during, and after perfusion of the coronary circulation with a cardioplegic solution. During perfusion, there was a highly significant reduction (P less than 0.001) in ventricular compliance; the mean cavity volume change decreased by 50% at a filling pressure of 12 mmHg. The loss of compliance was reversible and increased with coronary artery pressure. The magnitudes of the principal epicardial extensions, determined by homogeneous strain analysis, also decreased significantly (P less than 0.001) by an average of 30-40% at ventricular pressures of 4-12 mmHg. But there was no change in the pattern of epicardial deformations. These findings, and similar significant falls in epicardial in-plane rotation (P less than 0.05) and angular translation (P less than 0.001), suggest that the main mechanical effect of the coronary circulation is homogeneous and uniform and is, therefore, probably associated with the microcirculation. We propose that this effect may be modeled by treating the myocardium as a porous elastic medium swollen with an incompressible fluid rather than by an increase in ventricular wall thickness due to filling of the coronary vessels.

Animals↗
PubMed1991

Non-homogeneous analysis of three-dimensional transmural finite deformation in canine ventricular myocardium.

A new method has been developed for analyzing transmural distributions of finite deformation in canine ventricular myocardium without the need to assume that the strain in a finite volume of the wall is homogeneous. The three-dimensional nodal geometric parameters of bilinear-cubic or bilinear-quadratic finite elements are fitted by least squares to the measured coordinates of 12-18 radiopaque markers implanted in the left ventricular free wall. For six dog hearts, root-mean-squared errors in the fitted in-plane coordinates ranged from 0.079-0.556 mm in the end-diastolic reference state and 0.142-0.622 mm at end-systole. The corresponding error ranges in the radial coordinate were 0.042-0.264 mm at end-diastole and 0.106-0.279 mm at end-systole. Smoothly continuous transmural profiles of wall strain computed as the element deformed during the cardiac cycle from end-diastole to end-systole showed good agreement with the discrete results of conventional homogeneous analysis. Using the kinematics of a thick-walled incompressible cylinder, overall absolute errors due to the non-homogeneity of myocardial deformation were found to be reduced in the new analysis by 30-35% for typical experimental parameters. Overall relative errors were also reduced (from 23 to 20%). Since measurement errors in the reconstructed marker coordinates were spatially smoothed by the fitting procedure, noise in the computed deformations was also substantially attenuated, and transmural gradients of three-dimensional strain components could be obtained with improved accuracy. Hence physiological factors affected by transmural stress and strain distributions, such as myocardial blood flow, ischemia and hypertrophy, may be better understood.

Animals↗
PubMed1991

Passive material properties of intact ventricular myocardium determined from a cylindrical model.

The equatorial region of the canine left ventricle was modeled as a thick-walled cylinder consisting of an incompressible hyperelastic material with homogeneous exponential properties. The anisotropic properties of the passive myocardium were assumed to be locally transversely isotropic with respect to a fiber axis whose orientation varied linearly across the wall. Simultaneous inflation, extension, and torsion were applied to the cylinder to produce epicardial strains that were measured previously in the potassium-arrested dog heart. Residual stress in the unloaded state was included by considering the stress-free configuration to be a warped cylindrical arc. In the special case of isotropic material properties, torsion and residual stress both significantly reduced the high circumferential stress peaks predicted at the endocardium by previous models. However, a resultant axial force and moment were necessary to cause the observed epicardial deformations. Therefore, the anisotropic material parameters were found that minimized these resultants and allowed the prescribed displacements to occur subject to the known ventricular pressure loads. The global minimum solution of this parameter optimization problem indicated that the stiffness of passive myocardium (defined for a 20 percent equibiaxial extension) would be 2.4 to 6.6 times greater in the fiber direction than in the transverse plane for a broad range of assumed fiber angle distributions and residual stresses. This agrees with the results of biaxial tissue testing. The predicted transmural distributions of fiber stress were relatively flat with slight peaks in the subepicardium, and the fiber strain profiles agreed closely with experimentally observed sarcomere length distributions. The results indicate that torsion, residual stress and material anisotropy associated with the fiber architecture all can act to reduce endocardial stress gradients in the passive left ventricle.

Animals↗
PubMed1991

Transmural distribution of three-dimensional strain in the isolated arrested canine left ventricle.

Three-dimensional myocardial strains in seven isolated, potassium-arrested dog hearts were measured by biplane radiography of 3 transmural columns of 4-6 radiopaque beads implanted in the midanterior left ventricular free wall. Transmural distributions of strain during inflation of a left ventricular balloon to 20-30 mmHg were computed with respect to the zero pressure state. Magnitudes of the 3 principal strains increased in proportion to ventricular volume (0.0088, 0.0037, and -0.0059 ml-1). At a left ventricular pressure of 8 +/- 4 mmHg, mean circumferential (E11) and longitudinal strains (E22) were similar, increasing from epicardium (0.058 +/- 0.055 and 0.036 +/- 0.024) to subendocardium (0.139 +/- 0.102 and 0.120 +/- 0.084) as did the transmural (wall thinning) strain E33 (-0.053 +/- 0.071 to -0.128 +/- 0.083). Negative in-plane shear E12 was small (-0.008 to -0.052), consistent with a left-handed torsion of the left ventricular wall. Mean transverse shear strains E13 and E23 were small (-0.029 to 0.007) but showed considerable variability between hearts. Fiber strain had no significant transmural variation (P = 0.57). The principal axis of greatest strain was close to the fiber orientation on the epicardium (-15 degrees) but closer to the cross-fiber direction near the endocardium (-40 degrees). Therefore, the end-diastolic fiber lengths are maximized on the epicardium and minimized on the endocardium.

Animals↗
PubMed1989

Regional left ventricular epicardial deformation in the passive dog heart.

Epicardial wall motion was measured on the left ventricular free wall in six isolated potassium-arrested dog hearts using a biplane video technique. Significant regional variations in epicardial deformations were recorded during static ventricular filling. Epicardial stretches varied linearly with cavity volume, sometimes exceeding 20% at physiological left ventricular end-diastolic pressures. The maximum component of epicardial stretch and the derived wall thinning increased substantially from the base to the apex on both the anterior and the posterior free walls of the left ventricle. In five hearts, the direction of greatest epicardial stretch at moderate and high filling pressures coincided closely with the local epicardial fiber direction, suggesting that the left-handed epicardial fiber helices stretch preferentially during passive filling to maximize end-diastolic fiber lengths. Epicardial rotation was always counterclockwise, consistent with a reduction in the pitch of the fiber helix during filling. These results suggest that, on the epicardial surface, the passive myocardium is anisotropic with respect to the local fiber direction. We suggest that the resulting torsional shear acts to minimize transmural gradients of fiber stretch.

Animals↗
PubMed1987

Left ventricular epicardial deformation in isolated arrested dog heart.

We have developed a method for measuring epicardial deformation in the isolated arrested dog heart. A biplane video system was used to record the motion of discrete epicardial markers at midanterior sites (n = 4 hearts) and midposterior sites (n = 1) during quasi-static left ventricular (LV) filling. Experimental procedures, performed at room temperature, were completed within 20 min, and LV pressure-volume curves were repeatable and within the range of data presented by other authors. To obtain a complete description of local deformation, epicardial displacements derived from the video record were analyzed using homogeneous strain theory. Local epicardial strain was nonuniform; the mean ranges of midanterior major and minor extensions were 0-13.9 and 0-7.2%, respectively, for LV filling pressures of 0-20 mmHg. For the midanterior wall, the mean orientation of the major extension was 28-35 degrees below the LV circumference, compared with an orientation of approximately 62 degrees at the midposterior site. The results demonstrate the value of this preparation for studying passive ventricular mechanics and are not consistent with the predictions of mathematical models of ventricular stress and strain, in which it has been assumed that the material properties of the passive myocardium are isotropic.

Animals↗
PubMedDate not supplied

Regional myocardial mechanics: integrative computational models of flow-function relations.

Many cardiac disorders result in regionally altered myocardial mechanics. Although myocardial strain distributions can be measured experimentally and clinically, regional wall stresses must be computed from computational models. Combining these approaches can provide insight into the structural basis of regional dysfunction under conditions such as acute myocardial infarction and ischemia-reperfusion. Recently, 3-dimensional computational models have helped to elucidate the structural basis of the functional border zone adjacent to acutely ischemic myocardium. They have also shown that heterogeneous dysfunction in ischemic-reperfused stunned myocardium does not necessarily imply heterogeneous myofilament injury. Now that computational models are able to reproduce many complex features of the 3-dimensional patterns of regional myocardial deformation observed experimentally, we suggest possible roles for such integrative models in clinical diagnosis.

Animals↗
PubMedDate not supplied

History-dependent mechanical behavior of guinea-pig small intestine.

Measurement of pressure-volume relations is a commonly used technique to elucidate small intestinal stiffness. There is a lack of data on the relation between stiffness and history-dependent mechanical properties of the gastrointestinal tract. We aimed to distinguish between passive properties of the tissue that depend on the time-history of load (viscoelastic effects) versus those that depend on the maximum previous load (strain softening effects). Ten repeated pressure-volume relations were measured at each peak pressure level in six isolated, passive guinea-pig jejuni in vitro during balloon inflation and deflation cycles. With inflation to a new higher peak pressure (ranging from 3 to 15 mm Hg), the pressure-volume relation became less stiff, particularly in the low pressure range, without a significant change in unloaded jejunal volume. We computed the jejunal normalized volume change as a function of the integrated volume-time history and maximum volume. Analysis of covariance revealed significant dependence of the normalized volume change on the volume-time history (P < 0.001) and the maximum volume history (P < 0.001). Multiple linear regression analysis showed that approximately 90% of the history dependence could be attributed to the maximum volume. Most softening (loss of stiffness) happens in the low pressure range of the curve (0-3 mm Hg). We adopted the Johnson and Beatty strain softening theory and computed the volume amplification factor. This factor was shown to be a linear function of the normalized peak volume (r2 > 0.999). Since strain softening effects were significantly greater than viscoelastic effects, we conclude that history-dependent changes in jejunal stiffness are more likely to involve alterations to elastic rather than viscous structures in the tissue. These effects must be taken into account when performing balloon distension studies in the gastrointestinal tract for studying physiological and pathophysiological problems in which loading conditions are altered, e.g., mechanoreceptor studies in normal intestine and in acute and chronic obstruction, in order to have an accurate description of the biomechanics.

Analysis of Variance↗
PubMedDate not supplied

Measurement of orientation and distribution of cellular alignment and cytoskeletal organization.

Endothelial cells elongate and align with the direction of applied fluid shear stress. Previously, automated methods for analysis of cell orientation distribution have used Fourier- or fractal-based methods. We used intensity gradients in images of control and sheared endothelial cells to measure orientation distributions. Automated measurements of mean orientation and angular deviation compared favorably with manual measurements. There was a significantly greater angular deviation in images of control cells compared with sheared cells. Automated methods were also used to quantify organization of cytoskeletal fibers using the local angular deviation and a measure of the local coalignment of fibers called the coalignment ratio. The local angular deviation of microtubules and microfilaments was significantly smaller in sheared cells compared with control. The coalignment of cytoskeletal fibers was significantly greater in sheared cells. We conclude that image intensity gradients can be used rapidly, accurately, and objectively to measure cell orientation distributions and cytoskeletal filament organization.

Algorithms↗
PubMedDate not supplied

Regional myocardial perfusion and mechanics: a model-based method of analysis.

A new parametric model-based method has been developed that allows epicardial strain distributions to be computed on the left ventricular free wall in normal and ischemic myocardium and integrated with the regional distributions of anatomic and physiological measurements so that underlying relationships can be explored. An array of radiopaque markers was sewn on the anterior wall of the left ventricle (LV) in three anesthetized open-chest canines, and their positions were recorded using biplane video fluoroscopy before and 2 min after occlusion of the left anterior descending coronary artery. The three-dimensional (3D) anatomy of the LV and epicardial fiber angles were measured post-mortem using a 3D probe. A prolate spheroidal finite element model was fitted to the epicardial surface points (with <0.2 mm accuracy) and fiber angles (<5 degrees error). Regional myocardial blood flows (MBFs) were measured using fluorescent microspheres and fitted into the model (<0.3 ml min(-1) g(-1) error). Epicardial fiber and cross-fiber strain distributions were computed by allowing the model to deform from end-diastole to end-systole according to the recorded motion of the surface markers. Systolic fiber strain varied from -0.05 to 0.01 within the region of the markers during baseline, and regional MBF varied from 1.5 to 2.0 ml min(-1) g(-1). During 2 min ischemia, regional MBF was less than 0.3 ml min(-1) g(-1) in the ischemic region and 1.0 ml min(-1) g(-1) in the nonischemic region, and fiber strain ranged from 0.05 in the central ischemic zone to -0.025 in the remote nonischemic tissue. This analysis revealed a zone of impaired fiber shortening extending into the normally perfused myocardium that was significantly wider at the base than the apex. A validation analysis showed that a regularizing function can be optimized to minimize both fitting errors and numerical oscillations in the computed strain fields.

Animals↗