Myofiber angle distributions in the ovine left ventricle do not conform to computationally optimized predictions

Recent computational models of optimized left ventricular (LV) myofiber geometry that minimize the spatial variance in sarcomere length, stress, and ATP consumption have predicted that a midwall myofiber angle of 20 degrees and transmural myofiber angle gradient of 140 degrees from epicardium to endocardium is a functionally optimal LV myofiber geometry. In order to test the extent to which actual fiber angle distributions conform to this prediction, we measured local myofiber angles at an average of nine transmural depths in each of 32 sites (4 short-axis levels, 8 circumferentially distributed blocks in each level) in five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral and anterolateral wall near the papillary muscles, and -9 degrees in all other regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with spatial heterogeneity (averaging a low of 51 degrees in the basal posterior sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We conclude that midwall myofiber angles and transmural myofiber angle gradients in the ovine heart are regionally non-uniform and differ significantly from the predictions of present-day computationally optimized LV myofiber models. Myofiber geometry in the ovine heart may differ from other species, but model assumptions also underlie the discrepancy between experimental and computational results. To test the predictive capability of the current computational model would we propose using an ovine specific LV geometry and comparing the computed myofiber orientations to those we report herein.     

Dependence of local left ventricular wall mechanics on myocardial fiber orientation: a model study.

The dependence of local left ventricular (LV) mechanics on myocardial muscle fiber orientation was investigated using a finite element model. In the model we have considered anisotropy of the active and passive components of myocardial tissue, dependence of active stress on time, strain and strain rate, activation sequence of the LV wall and aortic afterload. Muscle fiber orientation in the LV wall is quantified by the helix fiber angle, defined as the angle between the muscle fiber direction and the local circumferential direction. In a first simulation, a transmural variation of the helix fiber angle from +60 degrees at the endocardium through 0 degrees in the midwall layers to -60 degrees at the epicardium was assumed. In this simulation, at the equatorial level maximum active muscle fiber stress was found to vary from about 110 kPa in the subendocardial layers through about 30 kPa in the midwall layers to about 40 kPa in the subepicardial layers. Next, in a series of simulations, muscle fiber orientation was iteratively adapted until the spatial distribution of active muscle fiber stress was fairly homogeneous. Using a transmural course of the helix fiber angle of +60 degrees at the endocardium, +15 degrees in the midwall layers and -60 degrees at the epicardium, at the equatorial level maximum active muscle fiber stress varied from 52 kPa to 55 kPa, indicating a remarkable reduction of the stress range. Moreover, the change of muscle fiber strain with time was more similar in different parts of the LV wall than in the first simulation. It is concluded that (1) the distribution of active muscle fiber stress and muscle fiber strain across the LV wall is very sensitive to the transmural distribution of the helix fiber angle and (2) a physiological transmural distribution of the helix fiber angle can be found, at which active muscle fiber stress and muscle fiber strain are distributed approximately homogeneously across the LV wall.     

MRI-based finite-element analysis of left ventricular aneurysm

Tagged MRI and finite-element (FE) analysis are valuable tools in analyzing cardiac mechanics. To determine systolic material parameters in three-dimensional stress-strain relationships, we used tagged MRI to validate FE models of left ventricular (LV) aneurysm. Five sheep underwent anteroapical myocardial infarction (25% of LV mass) and 22 wk later underwent tagged MRI. Asymmetric FE models of the LV were formed to in vivo geometry from MRI and included aneurysm material properties measured with biaxial stretching, LV pressure measurements, and myofiber helix angles measured with diffusion tensor MRI. Systolic material parameters were determined that enabled FE models to reproduce midwall, systolic myocardial strains from tagged MRI (630 +/- 187 strain comparisons/animal). When contractile stress equal to 40% of the myofiber stress was added transverse to the muscle fiber, myocardial strain agreement improved by 27% between FE model predictions and experimental measurements (RMS error decreased from 0.074 +/- 0.016 to 0.054 +/- 0.011, P < 0.05). In infarct border zone (BZ), end-systolic midwall stress was elevated in both fiber (24.2 +/- 2.7 to 29.9 +/- 2.4 kPa, P < 0.01) and cross-fiber (5.5 +/- 0.7 to 11.7 +/- 1.3 kPa, P = 0.02) directions relative to noninfarct regions. Contrary to previous hypotheses but consistent with biaxial stretching experiments, active cross-fiber stress development is an integral part of LV systole; FE analysis with only uniaxial contracting stress is insufficient. Stress calculations from these validated models show 24% increase in fiber stress and 115% increase in cross-fiber stress at the BZ relative to remote regions, which may contribute to LV remodeling.     

The dependency of fetal left ventricular biomechanics function on myocardium helix angle configuration

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV.

     

Why SIT Works: Normal Function Despite Typical Myofiber Pattern in Situs Inversus Totalis (SIT) Hearts Derived by Shear-induced Myofiber Reorientation

The left ventricle (LV) of mammals with Situs Solitus (SS, normal organ arrangement) displays hardly any interindividual variation in myofiber pattern and experimentally determined torsion. SS LV myofiber pattern has been suggested to result from adaptive myofiber reorientation, in turn leading to efficient pump and myofiber function. Limited data from the Situs Inversus Totalis (SIT, a complete mirror image of organ anatomy and position) LV demonstrated an essential different myofiber pattern, being normal at the apex but mirrored at the base. Considerable differences in torsion patterns in between human SIT LVs even suggest variation in myofiber pattern among SIT LVs themselves. We addressed whether different myofiber patterns in the SIT LV can be predicted by adaptive myofiber reorientation and whether they yield similar pump and myofiber function as in the SS LV. With a mathematical model of LV mechanics including shear induced myofiber reorientation, we predicted myofiber patterns of one SS and three different SIT LVs. Initial conditions for SIT were based on scarce information on the helix angle. The transverse angle was set to zero. During reorientation, a non-zero transverse angle developed, pump function increased, and myofiber function increased and became more homogeneous. Three continuous SIT structures emerged with a different location of transition between normal and mirrored myofiber orientation pattern. Predicted SIT torsion patterns matched experimentally determined ones. Pump and myofiber function in SIT and SS LVs are similar, despite essential differences in myocardial structure. SS and SIT LV structure and function may originate from same processes of adaptive myofiber reorientation.     

Regional ventricular wall thickening reflects changes in cardiac fiber and sheet structure during contraction: quantification with diffusion tensor MRI

Dynamic changes of myocardial fiber and sheet structure are key determinants of regional ventricular function. However, quantitative characterization of the contraction-related changes in fiber and sheet structure has not been reported. The objective of this study was to quantify cardiac fiber and sheet structure at selected phases of the cardiac cycle. Diffusion tensor MRI was performed on isolated, perfused Sprague-Dawley rat hearts arrested or fixed in three states as follows: 1) potassium arrested (PA), which represents end diastole; 2) barium-induced contracture with volume (BV+), which represents isovolumic contraction or early systole; and 3) barium-induced contracture without volume (BV-), which represents end systole. Myocardial fiber orientations at the base, midventricle, and apex were determined from the primary eigenvectors of the diffusion tensor. Sheet structure was determined from the secondary and tertiary eigenvectors at the same locations. We observed that the transmural distribution of the myofiber helix angle remained unchanged as contraction proceeded from PA to BV+, but endocardial and epicardial fibers became more longitudinally orientated in the BV- group. Although sheet structure exhibited significant regional variations, changes in sheet structure during myocardial contraction were relatively uniform across regions. The magnitude of the sheet angle, which is an index of local sheet slope, decreased by 23 and 44% in BV+ and BV- groups, respectively, which suggests more radial orientation of the sheet. In summary, we have shown for the first time that geometric changes in both sheet and fiber orientation provide a substantial mechanism for radial wall thickening independent of active components due to myofiber shortening. Our results provide direct evidence that sheet reorientation is a primary determinant of myocardial wall thickening.     

Residual strain in ischemic ventricular myocardium.

Structural remodeling during acute myocardial infarction affects ventricular wall stress and strain. To see whether acute myocardial infarction alters residual stress and strain in the left ventricle (LV), we measured opening angles in rat hearts after 30 minutes of left coronary artery occlusion. The mean opening angle in 18 ischemic hearts (51 +/- 20 deg) was significantly greater than in five sham-operated controls (29 +/- 11 deg, P < 0.05). To determine whether these alterations in residual strain may be associated with strain softening caused by systolic overstretch of the noncontracting ischemic tissue, we also measured opening angles in isolated hearts that had been passively inflated to high LV pressures (120 mmHg). The mean opening angle of the strain-softened hearts was not significantly different from the sham-operated hearts (34 +/- 27 deg, P = 0.74). Mean collagen area fractions in the myocardium were not significantly different between ischemic hearts (0.027 +/- 0.014) and the nonischemic group (0.022 +/- 0.011). Although there were significant differences in opening angles measured with ischemia, they do not appear to be a result of altered extracellular collagen content or softening associated with overstretch. Thus, there is a significant change in residual strain associated with acute ischemia that may be related to changes in collagen fiber structure, myocyte structure, or metabolic state.     

Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure

To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk (means +/- SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/- 0.030; P <0.05), whereas the apical site did not [P=not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 +/- 0.003 at 2 wk and 0.054 +/- 0.021 at final; both P <0.05), which contributed to a significant increase in wall thickness at the final study (0.181 +/- 0.047; P < 0.05), whereas the apical site did not (P=NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.     

Structure and conformation of the disulfide bond in dimeric lung surfactant peptides SP-B1-25 and SP-B8-25

Raman spectroscopy was used to determine the conformation of the disulfide linkage between cysteine residues in the homodimeric construct of the N-terminal alpha helical domain of surfactant protein B (dSP-B(1-25)). The conformation of the disulfide bond between cysteine residues in position 8 of the homodimer of dSP-B(1-25) was compared with that of a truncated homodimer (dSP-B(8-25)) of the peptide having a disulfide linkage at the same position in the alpha helix. Temperature-dependent Raman spectra of the S-S stretching region centered at approximately 500 cm(-1) indicated a stable, although highly strained disulfide conformation with a chi(CS-SC) dihedral angle of +/-10 degrees for the dSP-B(1-25) dimer. In contrast, the truncated dimer dSP-B(8-25) exhibited a series of disulfide conformations with the chi(CS-SC) dihedral angle taking on values of either +/-30 degrees or 85+/-20 degrees . For conformations with chi(CS-SC) close to the +/-90 degrees value, the Raman spectra of the 8-25 truncated dimers exhibited chi(SS-CC) dihedral angles of 90/180 degrees and 20-30 degrees . In the presence of a lipid mixture, both constructs showed a nu(S-S) band at approximately 488 cm(-1), corresponding to a chi(CS-SC) dihedral angle of +/-10 degrees . Polarized infrared spectroscopy was also used to determine the orientation of the helix and beta-sheet portion of both synthetic peptides. These calculations indicated that the helix was oriented primarily in the plane of the surface, at an angle of approximately 60-70 degrees to the surface normal, while the beta structure had approximately 40 degrees tilt. This orientation direction did not change in the presence of a lipid mixture or with temperature. These observations suggest that: (i) the conformational flexibility of the disulfide linkage is dependent on the amino acid residues that flank the cysteine disulfide bond, and (ii) in both constructs, the presence of a lipid matrix locks the disulfide bond into a preferred conformation.     

Optimizing ventricular fibers: uniform strain or stress,but not ATP consumption,leads to high efficiency

The aim of this study was to investigate the influence of fiber orientation in the left ventricular (LV) wall on the ejection fraction, efficiency, and heterogeneity of the distributions of developed fiber stress, strain and ATP consumption. A finite element model of LV mechanics was used with active properties of the cardiac muscle described by the Huxley-type cross-bridge model. The computed variances of sarcomere length (SL(var)), developed stress (DS(var)), and ATP consumption (ATP(var)) have several minima at different transmural courses of helix fiber angle. We identified only one region in the used design space with high ejection fraction, high efficiency of the LV and relatively small SL(var), DS(var), and ATP(var). This region corresponds to the physiological distribution of the helix fiber angle in the LV wall. Transmural fiber angle can be predicted by minimizing SL(var) and DS(var), but not ATP(var). If ATP(var) was minimized, then the transverse fiber angle was considerably underestimated. The results suggest that ATP consumption distribution is not regulating the fiber orientation in the heart.     

Direct measurement of transmural laminar architecture in the anterolateral wall of the ovine left ventricle: new implications for wall thickening mechanics

Laminar, or sheet, architecture of the left ventricle (LV) is a structural basis for normal systolic and diastolic LV dynamics, but transmural sheet orientations remain incompletely characterized. We directly measured the transmural distribution of sheet angles in the ovine anterolateral LV wall. Ten Dorsett-hybrid sheep hearts were perfusion fixed in situ with 5% buffered glutaraldehyde at end diastole and stored in 10% formalin. Transmural blocks of myocardial tissue were excised, with the edges cut parallel to local circumferential, longitudinal, and radial axes, and sliced into 1-mm-thick sections parallel to the epicardial tangent plane from epicardium to endocardium. Mean fiber directions were determined in each section from five measurements of fiber angles. Each section was then cut transverse to the fiber direction, and five sheet angles (beta) were measured and averaged. Mean fiber angles progressed nearly linearly from -41 degrees (SD 11) at the epicardium to +42 degrees (SD 16) at the endocardium. Two families of sheets were identified at approximately +45 degrees (beta(+)) and -45 degrees (beta(-)). In the lateral region (n = 5), near the epicardium, sheets belonged to the beta(+) family; in the midwall, to the beta(-) family; and near the endocardium, to the beta(+) family. This pattern was reversed in the basal anterior region (n = 4). Sheets were uniformly beta(-) over the anterior papillary muscle (n = 2). These direct measurements of sheet angles reveal, for the first time, alternating transmural families of predominant sheet angles. This may have important implications in understanding wall mechanics in the normal and the failing heart.     

Differences in the iliolumbar ligament and the transverse process of the L5 vertebra in young white and black people

The anatomy of the iliolumbar ligament (ILL) and the spatial orientation of the transverse process of the L5 vertebra were studied in 62 young black (n = 29) and white (n = 33) men and women during routine autopsy. The aim of the study was to determine possible racial differences in the structure and attachments of the iliolumbar ligament. The present study also investigated the spatial orientation of the transverse process of the L5 vertebra since the ILL has been reported to attach to the transverse process. The measurements of the iliolumbar ligament were carried out with a digital vernier caliper while the transverse process angles were measured with an adjustable protractor. The ligament in black people was made up of a single, markedly longer band compared to white people, where the ligament was made up of two shorter bands. The ILL measured 61.8 +/- 1.3 mm in black and 33.2 +/- 1.5 mm white men, and in black women 61.3 +/- 0.9 mm versus 32.2 +/- 1.2 mm in white women (p <0.01). Further, the ILL was markedly wider in black than white subjects (p <0.01). The horizontal and vertical angle also varied greatly between black and white subjects (p <0.01). These are previously unrecognized observations. Albeit unsubstantiated, these findings may have implications for understanding the etiology of various low back stress problems.     

Fiber stress profiles in the left ventricle of the heart during diastole: Effects of distension and hypertrophy

Pressure-volume and volume-dimensions relationships, obtained from excised dog left ventricles were used for calculating the stresses acting along the longitudinal axis of the individual myocardial fibers. The calculations were based on a set of empirical and theoretical equations. The pressure-volume relationship as well as the volume-dimensions relationships for the excised left ventricle were expressed in the form of empirical equations; the fiber orientation was written as a function of the fiber location within the left ventricular wall; finally, the fiber stress was determined by means of theoretically derived formulas. Simultaneous solutions for the fibers of a meridian cut through the left ventricular myocardial shell were obtained by means of a digital computer and presented in the form of diagrams. The results showed that at low degrees of distension of the left ventricle there are two zones of higher stresses at the equatorial area, one near the epicardium and one near the endocardium. As the distension proceeds under the effect of progressively increasing intraventricular pressure, these two zones become less well defined, whereas a new zone of higher stresses appears near the apex. At high degrees of distension, the ventricle assumes a more spherical shape and the equatorial zones of higher stresses are replaced by zones of lower stresses. Increase in the myocardial mass results in appearance of the equatorial lower stress zones at lower degrees of distension.     

Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation

In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of \({\sim }8^\circ \) predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work \(({\sim }18\,\%)\) and in global pump work \(({\sim }17\,\%)\) in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information.

     

Transmembrane four-helix bundle of influenza A M2 protein channel: structural implications from helix tilt and orientation.

The transmembrane portion of the M2 protein from the Influenza A virus has been studied in hydrated dimyristroylphosphotidylcholine lipid bilayers with solid-state NMR. Orientational constraints were obtained from isotopically labeled peptide samples mechanically aligned between thin glass plates. 15N chemical shifts from single site labeled samples constrain the molecular frame with respect to the magnetic field. When these constraints are applied to the peptide, modeled as a uniform alpha-helix, the tilt of the helix with respect to the bilayer normal was determined to be 33 degrees +/- 3 degrees. Furthermore, the orientation about the helix axis was also determined within an error of +/- 30 degrees. These results imply that the packing of this tetrameric protein is in a left-handed four-helix bundle. Only with such a large tilt angle are the hydrophilic residues aligned to the channel axis.     

Bioinjection treatment: Effects of post-injection residual stress on left ventricular wall stress

Injection of biomaterials into diseased myocardium has been associated with decreased myofiber stress, restored left ventricular (LV) geometry and improved LV function. However, its exact mechanism(s) of action remained unclear. In this work, we present the first patient-specific computational model of biomaterial injection that accounts for the possibility of residual strain and stress introduced by this treatment. We show that the presence of residual stress can create more heterogeneous regional myofiber stress and strain fields. Our simulation results show that the treatment generates low stress and stretch areas between injection sites, and high stress and stretch areas between the injections and both the endocardium and epicardium. Globally, these local changes are translated into an increase in average myofiber stress and its standard deviation (from 6.9±4.6 to 11.2±48.8 kPa and 30±15 to 35.1±50.9 kPa at end-diastole and end-systole, respectively). We also show that the myofiber stress field is sensitive to the void-to-size ratio. For a constant void size, the myofiber stress field became less heterogeneous with decreasing injection volume. These results suggest that the residual stress and strain possibly generated by biomaterial injection treatment can have large effects on the regional myocardial stress and strain fields, which may be important in the remodeling process.     

Heterogeneous transmural proteoglycan distribution provides a mechanism for regulating residual stresses in the aorta

The arterial wall contains a significant amount of charged proteoglycans, which are inhomogeneously distributed, with the greatest concentrations in the intimal and medial layers. The hypothesis of this study is that the transmural distribution of proteoglycans plays a significant role in regulating residual stresses in the arterial wall. This hypothesis was first tested theoretically, using the framework of mixture theory for charged hydrated tissues, and then verified experimentally by measuring the opening angle of rat aorta in NaCl solutions of various ionic strengths. A three-dimensional finite element model of aortic ring, using realistic values of the solid matrix shear modulus and proteoglycan fixed-charge density, yielded opening angles and changes with osmolarity comparable to values reported in the literature. Experimentally, the mean opening angle in isotonic saline (300 mosM) was 15 +/- 17 degrees and changed to 4 +/- 19 degrees and 73 +/- 18 degrees under hypertonic (2,000 mosM) and hypotonic (0 mosM) conditions, respectively (n = 16). In addition, the opening angle in isotonic (300 mosM) sucrose, an uncharged molecule, was 60 +/- 16 degrees (n = 11), suggesting that the charge effect, not cellular swelling, was the major underlying mechanism for these observations. The extent of changes in opening angle under osmotic challenges suggests that transmural heterogeneity of fixed-charge density plays a crucial role in governing the zero-stress configuration of the aorta. A significant implication of this finding is that arterial wall remodeling in response to altered wall stresses may occur via altered deposition of proteoglycans across the wall thickness, providing a novel mechanism for regulating mechanical homeostasis in vascular tissue.     

Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation

Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.     

Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (sigma)-strain (epsilon) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear sigma-epsilon relations were obtained in control (n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 +/- 1,433 vs. 1,435 +/- 467 g/cm(2), P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload.     

A two-phase finite element model of the diastolic left ventricle

A porous medium finite element model of the passive left ventricle is presented. The model is axisymmetric and allows for finite deformation, including torsion about the axis of symmetry. An anisotropic quasi-linear viscoelastic constitutive relation is implemented in the model. The model accounts for changing fibre orientation across the myocardial wall. During passive filling, the apex rotates in a clockwise direction relative to the base for an observer looking from apex to base. Within an intraventricular pressure range of 0-3 kPa the rotation angle of all nodes remained below 0.1 rad. Diastolic viscoelasticity of myocardial tissue is shown to reduce transmural differences of preload-induced sarcomere stretch and to generate residual stresses in an unloaded ventricular wall, consistent with the observation of opening angles seen when the heart is slit open. It is shown that the ventricular model stiffens following an increase of the intracoronary blood volume. At a given left ventricular volume, left ventricular pressure increases from 1.5 to 2.0 kPa when raising the intracoronary blood volume from 9 to 14 ml (100 g)-1 left ventricle.