Biomedical subjects

A D McCulloch

Publications and source records attributed to A D McCulloch.

At least 55 records · Page 3Linked to original sources

PubMed1997

Three-dimensional residual strain in midanterior canine left ventricle.

All previous studies of residual strain in the ventricular wall have been based on one- or two-dimensional measurements. Transmural distributions of three-dimensional (3-D) residual strains were measured by biplane radiography of columns of lead beads implanted in the midanterior free wall of the canine left ventricle (LV). 3-D bead coordinates were reconstructed with the isolated arrested LV in the zero-pressure state and again after local residual stress had been relieved by excising a transmural block of tissue. Nonhomogeneous 3-D residual strains were computed by finite element analysis. Mean +/- SD (n = 8) circumferential residual strain indicated that the intact unloaded myocardium was prestretched at the epicardium (0.07 +/- 0.06) and compressed in the subendocardium (-0.04 +/- 0.05). Small but significant longitudinal shortening and torsional shear residual strains were also measured. Residual fiber strain was tensile at the epicardium (0.05 +/- 0.06) and compressive in the subendocardium (-0.01 +/- 0.04), with residual extension and shortening, respectively, along structural axes parallel and perpendicular to the laminar myocardial sheets. Relatively small residual shear strains with respect to the myofiber sheets suggest that prestretching in the plane of the myocardial laminae may be a primary mechanism of residual stress in the LV.

Animals↗

PubMed1996

Transmural changes in stress-free myocyte morphology during pressure overload hypertrophy in the rat.

Cellular hypertrophy can alter the distribution of residual stress in the myocardium, hence can affect active and passive ventricular mechanics. It is hypothesized that an increase in stress-free cell cross-sectional area will tend to increase residual stresses. Therefore transmural distributions of myocyte cross-sectional areas and global ventricular dimensions in young rats 0-21 days following thoracic aortic handling with sham-operated and unoperated control groups were measured in tissue free of all external and residual stresses. Cell cross-sectional area increased in the stress-free state and was uniform across the wall except at 21 days when there was a transmural gradient with cells at the endocardium 46% larger in diameter than those in the outer wall. Cell area increased from a mean of 156 +/- 30 microM2 at 0 days to a mean of 627 +/- 164 microM2 at 21 days, although during this time there were no statistical changes in the opening angles of stress-free tissue sections. Because the time course of opening angle did not follow the changes in cell thickening, the cellular growth measured in this study is probably not the only factor responsible for the distribution of residual stress.

Analysis of Variance↗

PubMed1996

Distributed mechanics of the canine right ventricle: effects of varying preload.

Fundamental questions in the mechanics of the right ventricle (RV) include: what are the distributions of diastolic and systolic strains across the RV epicardium and how do these strains change with increasing preload? Arrays (approximately 4 x 4 cm) of 25 to 30 lead markers were sutured to the epicardium of the RV anterior free wall in 6 open-chest, anesthetized dogs. Biplane cinéradiography (16 mm, 120 fps) was used to track marker positions throughout the cardiac cycle as loading conditions were altered by intravenous volume infusion. Continuous two-dimensional nonhomogeneous deformations were estimated across the region by fitting high-order finite element surfaces to the three-dimensional marker coordinates in successive ciné frames. End-systolic strains referred to end-diastole did not change with increasing preload, but did exhibit considerable longitudinal variation, e.g. the principal strain associated with maximal shortening (E1) was more than twice as great nearer the apex (E1 = -0.18 +/- 0.08) than in more basal (E1 = -0.09 +/- 0.05) regions. However, large amounts of lengthening occurred during diastolic inflation. End-diastolic extensional strains referred to an unloaded configuration were moderate at low pressure (E2 = 0.13 +/- 0.08) but increased to large values at high preloads (E2 = 0.28 +/- 0.11). End-diastolic strains also showed considerable longitudinal variation, i.e. near the base lengthening (E2 = 0.31 +/- 0.13) tended to be much greater than near the apex (E2 = 0.15 +/- 0.12). These results indicate that both diastolic sarcomere lengths and systolic sarcomere shortening increase in proportion to diastolic loading leaving end-systolic sarcomere strains unchanged.

Animals↗

PubMed1996

A three-dimensional finite element method for large elastic deformations of ventricular myocardium: I--Cylindrical and spherical polar coordinates.

A three-dimensional Galerkin finite element method was developed for large deformations of ventricular myocardium and other incompressible, nonlinear elastic, anisotropic materials. Cylindrical and spherical elements were used to solve axisymmetric problems with r.m.s. errors typically less than 2 percent. Isochoric interpolation and pressure boundary constraint equations enhanced low-order curvilinear elements under special circumstances (69 percent savings in degrees of freedom, 78 percent savings in solution time for inflation of a thick-walled cylinder). Generalized tensor products of linear Lagrange and cubic Hermite polynomials permitted custom elements with improved performance, including 52 percent savings in degrees of freedom and 66 percent savings in solution time for compression of a circular disk. Such computational efficiencies become significant for large scale problems such as modeling the heart.

Animals↗

PubMed1996

A three-dimensional finite element method for large elastic deformations of ventricular myocardium: II--Prolate spheroidal coordinates.

A three-dimensional finite element method for nonlinear finite elasticity is presented using prolate spheroidal coordinates. For a thick-walled ellipsoidal model of passive anisotropic left ventricle, a high-order (cubic Hermite) mesh with 3 elements gave accurate continuous stresses and strains, with a 69 percent savings in degrees of freedom (dof) versus a 70-element standard low-order model. A custom mixed-order model offered 55 percent savings in dof and 39 percent savings in solution time compared with the low-order model. A nonsymmetric 3D model of the passive canine LV was solved using 16 high-order elements. Continuous nonhomogeneous stresses and strains were obtained within 1 hour on a laboratory workstation, with an estimated solution time of less than 4 hours to model end-systole. This method represents the first practical opportunity to solve large-scale anatomically detailed models for cardiac stress analysis.

Animals↗

PubMed1996

An equibiaxial strain system for cultured cells.

We developed a device that applies homogeneous equibiaxial strains of 0-10% to a cell culture substrate and quantitatively verified transmission of substrate deformation to cultured cardiac cells. Clamped elastic membranes in both single-well and multiwell versions of the device are uniformly stretched by indentation with a plastic ring, resulting in strain that is directly proportional to the pitch-to-radius ratio. Two-dimensional deformations were measured by tracking fluorescent microspheres attached to the substrate and to cultured adult rat cardiac fibroblasts. For nominal stretches up to 18%, strains along circumferential and radial axes were equal in magnitude and homogeneously distributed with negligible shear. For 5% stretch, circumferential and radial strains in the substrate were 0.046 +/- 0.005 and 0.048 +/- 0.004 [not significant (NS)], respectively, and shear strain was 0.001 +/- 0.003 (NS). Calibration of both single-well and multiwell versions permits strain selection by device rotation. The reproducible application and quantification of homogeneous equibiaxial strain in cultured cells provides a quantitative approach for correlating mechanical stimuli to cellular transduction mechanisms.

Animals↗

PubMed1996

Comparison of two techniques for measuring two-dimensional strain in rat left ventricles.

Measurements of regional deformation in the left ventricle are needed to understand the structural basis of ventricular function. Two techniques were employed to measure two-dimensional strain in the intact, beating rat heart. Rats were anesthetized and ventilated, and the chest of each rat was opened. Homogeneous two-dimensional strains were measured during the cardiac cycle relative to end diastole with either a triangle of miniature (0.3-0.5 mm) piezoelectric crystals implanted at midwall or with three epicardial surface markers imaged with a 60-Hz video system. Average heart rate was 303 +/- 37 beats/min, end-diastolic pressure was 2 +/- 2 mmHg, and peak-systolic pressure was 106 +/- 31 mmHg in all of the hearts. In general, strains during the cardiac cycle showed similar trends to those previously reported in the dog. The magnitudes of peak systolic cardiac strains on the epicardium and at midwall were -0.076 +/- 0.055, -0.068 +/- 0.014 (circumferential), -0.102 +/- 0.040, -0.082 +/- 0.039 (longitudinal), and 0.065 +/- 0.016, 0.064 +/- 0.043 (in-plane shear). There were mechanical side effects due to the crystal implantation that may limit the usefulness of this technique in its present form in the contracting rat heart. The epicardial surface technique does not have these side effects and will allow measurements of regional systolic cardiac function in rats with pathological interventions or genetic modifications that may alter regional ventricular function.

Animals↗

PubMed1995

Transmural distribution of capillary morphology as a function of coronary perfusion pressure in the resting canine heart.

Changes in coronary perfusion pressure lead to alterations in intracoronary myocardial volume that may be associated with regionally altered microvascular morphology. Transmural variations in coronary capillary geometry were quantified as a function of coronary perfusion pressure in glutaraldehyde-fixed canine hearts. Capillary volume fractions, diameter, numerical density, anisotropy, and sarcomere length were measured using computer analysis of light microscopic images of sections taken transverse or longitudinal to the muscle fiber axis. Capillary volume was 4-6% of myocardial wall volume and exhibited a significant transmural gradient, increasing from epicardium to endocardium. Vessels 4 to 5 microns in diameter with a density of 2900 mm-2 appear to increase in diameter and alter their cross-sectional shape with increasing pressure, rather than increasing in number, suggesting an effective distensibility of approximately 0.007 mm Hg-1. Quantification of vessel anisotropy was directly related to cross-sectional shape and demonstrated that the capillaries are highly oriented. These findings indicate that intramyocardial capacitance is at least in part associated with nonhomogeneous changes in coronary capillary morphology with altered perfusion pressure.

Animals↗

PubMed1995

Active force in rabbit ventricular myocytes.

Although recent technical advances have established the feasibility of force measurements in single cardiac myocytes, the physiological relevance of this model has not been fully evaluated. We measured active force and sarcomere length in single rabbit left ventricular myocytes and compared their physiological responses to changes in stimulus interval, calcium concentration and sarcomere length to results from isolated papillary muscles. Myocytes were attached to two poly-L-lysine-coated glass plates and force was measured with a capacitive force transducer (Cambridge 406A). Stable recordings from a continuously contracting myocyte could be maintained for over 1 h. In five cells, increasing stimulus interval significantly decreased active force development. This force-stimulus interval relation was similar to that obtained from papillary muscles. In one cell, we obtained a force-length relation that was similar to force-length relations from multicellular preparations. Active stresses (active forces normalized by cross-sectional area) were of similar magnitude when comparing myocytes (at slack length) and papillary muscles (at 85% of Lmax). These results confirm the physiological relevance of force measurements obtained from intact mammalian cardiac myocytes.

Analysis of Variance↗

PubMed1995

Finite element stress analysis of left ventricular mechanics in the beating dog heart.

A three-dimensional finite element model was used to explore whether or not transmural distributions of end-diastolic and end-systolic fiber stress are uniform from the apex to the base of the canine left ventricular wall. An elastance model for active fiber stress was incorporated in an axisymmetric model that accurately represented the geometry and fiber angle distribution of the anterior free wall. The nonlinear constitutive equation for the resting myocardium was transversely isotropic with respect to the local fiber axis. Transmural distributions of end-diastolic fiber stress became increasingly nonuniform from midventricle toward the apex or the base. At a typical diastolic left ventricular pressure (1 kPa), the differences between largest and smallest fiber stresses were only 0.5 kPa near midventricle, compared with 4.6 kPa at the apex, and 3.3 kPa at the base. Transmural fiber stress differences at end-systole (14 kPa) were relatively small in regions from the base to the midventricle (13-22 kPa), but were larger between midventricle and the apex (30-43 kPa). All six three-dimensional end-diastolic strain components were within or very close to one standard deviation of published measurements through the midanterior left ventricular free wall of the passive canine heart [Omens et al., Am. J. Physiol. 261, H918-H928 (1991)]. End-systolic in-plane normal and shear strains also agreed closely with published experimental measurements in the beating dog heart [Waldman et al., Circ. Res. 63, 550-562 (1988)]. The results indicate that, unlike in the midventricle region that has been studied most fully, there may be significant regional nonhomogeneity of fiber stress in the normal left ventricle associated with regional variations in shape and fiber angle.

Animals↗

PubMed1995

Angiotensin II stimulates the autocrine production of transforming growth factor-beta 1 in adult rat cardiac fibroblasts.

Angiotensin II (Ang II) has been implicated in the development of cardiac hypertrophy and myocardial fibrosis. While recent in vivo and in vitro studies performed in cultured cardiac myocytes and fibroblasts support this role for Ang II, the mechanisms of Ang II action at the cellular level remain unclear. In the present study, we postulated that Ang II action in adult cardiac fibroblasts may stimulate the autocrine production and release of transforming growth factor-beta 1 (TGF-beta 1), a known regulator of cardiac fibroblast and myocyte function. We examined the ability of Ang II to regulate the gene expression, biological activity, and protein production of TGF-beta 1 in cultured adult rat cardiac fibroblasts. Treatment of fibroblast cultures with Ang II (10(-9) M) induced a two-fold increase in TGF-beta 1 mRNA levels within 4 h that was sustained through 24 h (P < 0.01). TGF-beta 1-like activity in Ang II-treated cultures was significantly increased compared with control as measured by bioassay (P < 0.001). Specificity for TGF-beta 1-like activity was confirmed through its neutralization with a TGF-beta 1 specific antibody (100 micrograms/ml). Total concentration of TGF-beta 1 (latent plus active forms) in conditioned media from Ang II-treated cardiac fibroblasts was also found to be greater than control (P < 0.01). These findings suggest that the effects of Ang II in the adult myocardium may be mediated in part by autocrine/paracrine mechanisms, including the production and release of TGF-beta 1 by cardiac fibroblasts.

Angiotensin II↗

PubMed1994

Stress-dependent finite growth in soft elastic tissues.

Growth and remodeling in tissues may be modulated by mechanical factors such as stress. For example, in cardiac hypertrophy, alterations in wall stress arising from changes in mechanical loading lead to cardiac growth and remodeling. A general continuum formulation for finite volumetric growth in soft elastic tissues is therefore proposed. The shape change of an unloaded tissue during growth is described by a mapping analogous to the deformation gradient tensor. This mapping is decomposed into a transformation of the local zero-stress reference state and an accompanying elastic deformation that ensures the compatibility of the total growth deformation. Residual stress arises from this elastic deformation. Hence, a complete kinematic formulation for growth in general requires a knowledge of the constitutive law for stress in the tissue. Since growth may in turn be affected by stress in the tissue, a general form for the stress-dependent growth law is proposed as a relation between the symmetric growth-rate tensor and the stress tensor. With a thick-walled hollow cylinder of incompressible, isotropic hyperelastic material as an example, the mechanics of left ventricular hypertrophy are investigated. The results show that transmurally uniform pure circumferential growth, which may be similar to eccentric ventricular hypertrophy, changes the state of residual stress in the heart wall. A model of axially loaded bone is used to test a simple stress-dependent growth law in which growth rate depends on the difference between the stress due to loading and a predetermined growth equilibrium stress.

Bone Development↗

PubMed1994

A collocation--Galerkin finite element model of cardiac action potential propagation.

A new computational method was developed for modeling the effects of the geometric complexity, nonuniform muscle fiber orientation, and material inhomogeneity of the ventricular wall on cardiac impulse propagation. The method was used to solve a modification to the FitzHugh-Nagumo system of equations. The geometry, local muscle fiber orientation, and material parameters of the domain were defined using linear Lagrange or cubic Hermite finite element interpolation. Spatial variations of time-dependent excitation and recovery variables were approximated using cubic Hermite finite element interpolation, and the governing finite element equations were assembled using the collocation method. To overcome the deficiencies of conventional collocation methods on irregular domains, Galerkin equations for the no-flux boundary conditions were used instead of collocation equations for the boundary degrees-of-freedom. The resulting system was evolved using an adaptive Runge-Kutta method. Converged two-dimensional simulations of normal propagation showed that this method requires less CPU time than a traditional finite difference discretization. The model also reproduced several other physiologic phenomena known to be important in arrhythmogenesis including: Wenckebach periodicity, slowed propagation and unidirectional block due to wavefront curvature, reentry around a fixed obstacle, and spiral wave reentry. In a new result, we observed wavespeed variations and block due to nonuniform muscle fiber orientation. The findings suggest that the finite element method is suitable for studying normal and pathological cardiac activation and has significant advantages over existing techniques.

Action Potentials↗

PubMed1994

Nonuniform muscle fiber orientation causes spiral wave drift in a finite element model of cardiac action potential propagation.

INTRODUCTION: Reentrant tachyarrhythmias are thought to involve spiral waves of excitation and recovery that may be nonstationary. The effect of muscle fiber curvature on spiral and planar wave propagation was studied using a computational model. METHODS AND RESULTS: Two-dimensional anisotropic cardiac propagation was modeled using a finite element method to solve a modification of the FitzHugh-Nagumo equations. Spiral waves that propagated stably about a fixed core in tissue with a uniform fiber orientation were found to drift at an oblique angle to the fibers when the fibers curved. The drift velocity was linearly related to the fiber angle gradient and was 10% of the longitudinal propagation velocity with a gradient of 4 degree/cm. Planar wavefronts were also affected by fiber curvature. The maximal upstroke rate, propagation velocity, and the action potential amplitude all increased when the fibers curved toward the wavefront and decreased when they curved away. For example, when the fibers curved toward the wavefront with a moderate gradient of 15 degree/cm, maximal upstroke rate increased 74%, transverse propagation velocity increased 65%, and action potential amplitude increased 9%. This phenomenon caused the spiral wave drift: As a spiral wave traverses a cycle, the angle between the wavefront at the wavetip and the fibers changes periodically, thus altering the propagation parameters. These periodic changes affect the instantaneous radius of curvature of the wavetip path, which results in drift. CONCLUSION: Spiral and planar waves are affected by muscle fiber curvature. The resulting dynamics may be important in determining the lifetime and stability of reentrant arrhythmias.

Action Potentials↗

PubMed1994

Contribution of collagen matrix to passive left ventricular mechanics in isolated rat hearts.

Although it makes up only 2-6% of left ventricular dry weight, collagen is thought to be the major structural protein determining passive ventricular stiffness. However, the relationship between structure of the extracellular matrix and passive mechanics is not understood. Hence, to deplete the collagen matrix, 16 rat hearts were perfused with bacterial collagenase for 60 min. Quantitative morphology using picrosirius red revealed a 36% decrease in collagen area fraction predominantly in the medium-sized fibers. Scanning electron microscopy revealed damage to the endomysial struts. Passive pressure-volume curves showed increases in left ventricular volume at all pressures (from 0.203 +/- 0.061 to 0.265 +/- 0.061 ml at 5 mmHg, P < 0.0001). Strain during loading, calculated from lengths obtained from a triplet of piezoelectric crystals, was unchanged with collagen depletion. However, remodeling strain computed from the collagenase-treated state referred to the Krebs solution-treated state at the same ventricular pressure showed both circumferential (0.145 +/- 0.166 to 0.170 +/- 0.158) and longitudinal (0.070 +/- 0.120 to 0.068 +/- 0.069) stretching. Sarcomere lengths increased at all depths (5.2% at midwall). Thus alterations in the extracellular matrix lead to increased ventricular volume and sarcomere lengths without altering ventricular compliance.

Animals↗

PubMed1994

Gradients of epicardial strain across the perfusion boundary during acute myocardial ischemia.

To study the mechanical interaction between acutely ischemic and adjacent perfused myocardium, nonhomogeneous distributions of end-systolic epicardial strain were measured using an array of radiopaque beads sewn on the left ventricular free wall of the pig during complete left circumflex coronary artery occlusion. The midwall perfusion boundary, demarcated by postmortem dye injection, was reconstructed over the span of the epicardial array. During ischemia, circumferential and longitudinal shortening remained significantly depressed up to 13 mm outside the ischemic region near the base of the ventricle, up to 8-9 mm at the midventricle, but only 0-1 mm near the apex (P < 0.05). Gradients of circumferential and longitudinal strain across the boundary were significantly different during both baseline conditions and acute ischemia (P = 0.0001). However, gradients of the change in the strain from baseline to ischemia were not different for the two components. These results support the concept that direction-dependent differences in the strain gradients across the boundary during ischemia were due to the preservation of the baseline regional variations of strain combined with a loss of systolic function in the ischemic region.

Animals↗

PubMed1994

Three-dimensional transmural mechanical interaction between the coronary vasculature and passive myocardium in the dog.

The "garden hose" effect of coronary perfusion on diastolic left ventricular (LV) mechanics has been proposed to cause changes in systolic function by altering diastolic sarcomere length. We measured transmural distributions of three-dimensional shape change using radiopaque markers implanted in the LV free wall of eight isolated arrested canine hearts as functions of coronary arterial perfusion pressure (Pp) and LV pressure (PLV) and related these deformations to the local muscle fiber architecture. Increased Pp from 0 to 110 mm Hg produced a 10% reduction in LV chamber volume (P < .01) and 25% to 40% decreases in local three-dimensional wall strain at matched PLV, indicating myocardial stiffening. Significant decreases in the magnitudes of local deformation occurred preferentially in the cross-fiber and radial directions (P < .02), with no change in fiber strain. This suggests that changing coronary Pp does not alter diastolic fiber length; hence, the Frank-Starling law may not mediate the Gregg effect. Since the myocardial microvessels are primarily oriented parallel to the muscle fibers, the observed myocardial stiffening occurs in the directions transverse to the microvessels rather than along their length. Local myocardial wall volume in the unloaded LV demonstrated a uniform 5% increase from the unperfused state to Pp of 50 mm Hg. With further increases in Pp up to 110 mm Hg, the change in regional wall volume from the unperfused state developed a substantial transmural gradient increasing by 7% at the epicardium and 15% at the subendocardium. This reflects a significant increase (P < .02) in intramyocardial coronary capacitance from epicardium to endocardium, which may be related to a transmural gradient in coronary distensibility or vascularity.

Animals↗

PubMed1993

Measurement of strain and analysis of stress in resting rat left ventricular myocardium.

A technique has been developed for measuring two-dimensional strains in the left ventricle of the isolated arrested rat heart subjected to passive ventricular loading. The pressure-volume relationship was found in eight hearts during inflation of a left ventricular balloon. With the zero-pressure state as reference, in-plane strain components were determined using a triangle of ultrasonic dimension transducers (0.6-0.8 mm diameter) placed 3-6 mm apart in the midwall of the left ventricle. Mean circumferential (fiber) strain was larger than longitudinal (cross-fiber) strain (0.108 +/- 0.045, 0.055 +/- 0.045, respectively, at 11 mmHg), and shear strain (-0.048 +/- 0.029) was negative, consistent with left-handed torsion. The in-plane angle of greatest stretch was uniform with inflation (range = -26.5 degrees to -34.5 degrees). The equatorial region of the left ventricle was modeled with finite element analysis of a transversely isotropic thick-walled cylindrical shell subjected to internal loading and axial forces. The material parameters of an exponential strain energy function were optimized so that the least-squares difference between the predicted and the measured midwall strains was minimized. Material properties, stress and strain in the rat heart were compared to values predicted for the dog. In both species the tissue was stiffer in the fiber direction than in the cross-fiber direction. The ratio of fiber to cross-fiber stiffness was lower in the rat (2.50) than in the dog (5.24) at low loads and approximately equal at higher loads (1.63 and 1.39, respectively). The computational and experimental analyses showed that the larger shear strain and more nonuniform in-plane extension in the rat may be an indication of significantly different anisotropic material properties in these two species, and implies differences in the collagen ultrastructure.

Animals↗