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.     

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.     

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.     

Stress Distribution in the Canine Left Ventricle during Diastole and Systole

A model is proposed for stress analysis of the left ventricular wall (LV wall) based on the realistic assumption that the myocardium is essentially composed of fiber elements which carry only axial tension and vary in orientation through the wall. Stress analysis based on such a model requires an extensive study of muscle fiber orientation and curvature through the myocardium. Accordingly, the principal curvatures were studied at a local site near the equator in ten dog hearts rapidly fixed in situ at end diastole and end systole; the fiber orientation for these hearts had already been established in a previous study. The principal radii of curvature were (a) measured by fitting templates to the endocardial and epicardial wall surfaces in the circumferential and longitudinal directions and (b) computed from measured lengths of semiaxes of ellipsoids of revolution representing the LV wall (“ellipsoid” data). The wall was regarded as a tethered set of nested shells, each having a unique fiber orientation. Results indicate the following. (a) Fiber curvature, k, is maximum at midwall at end systole; this peak shifts towards endocardium at end diastole. (b) The pressure or radial stress through the wall decreases more rapidly near the endocardium than near the epicardium at end diastole and at end systole when a constant tension is assumed for each fiber through the wall. (c) At end diastole the curve for the circumferential stress vs. wall thickness is convex with a maximum at midwall. In the longitudinal direction the stress distribution curve is concave with a minimum at midwall. Similar distributions are obtained at end systole when a constant tension is assumed for each fiber through the wall. (d) The curvature and stress distributions obtained by direct measurements at a selected local site agree well with those computed from “ellipsoid” data.     

Strain-based estimation of time-dependent transmural myocardial architecture in the ovine heart

Left ventricular myofibers are connected by an extensive extracellular collagen matrix to form myolaminar sheets. Histological cardiac tissue studies have previously observed a pleated transmural distribution of sheets in the ovine heart, alternating sign of the sheet angle from epicardium to endocardium. The present study investigated temporal variations in myocardial fiber and sheet architecture during the cardiac cycle. End-diastolic histological measurements made at subepicardium, midwall, and subendocardium at an anterior-basal and a lateral-equatorial region of the ovine heart, combined with transmural myocardial Lagrangian strains, showed that the sheet angle but not the fiber angle varied temporally throughout the cardiac cycle. The magnitude of the sheet angle decreased during systole at all transmural depths at the anterior-basal site and at midwall and subendocardium depths at the lateral-equatorial site, making the sheets more parallel to the radial axis. These results support a previously suggested accordion-like wall-thickening mechanism of the myocardial sheets.     

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.     

Dynamics of intramural scroll waves in three-dimensional continuous myocardium with rotational anisotropy.

It has been suggested that reentrant activity in three-dimensional cardiac muscle may be organized as a scroll wave rotating around a singularity line called the filament. Experimental studies indicate that filaments are often concealed inside the ventricular wall and consequently, scroll waves do not manifest reentrant activity on the surface. Here we analyse how such concealed scroll waves are affected by a twisted anisotropy resulting from rotation of layers of muscle fibers inside the ventricular wall. We used a computer model of a ventricular slab (15x15x15 mm(3)) with a fiber twist of 120 degrees from endocardium to epicardium. The action potential was simulated using FitzHugh-Nagumo equations. Scroll waves with rectilinear filaments were initiated at various depths of the slab and at different angles with respect to fiber orientation. The analysis shows that independent of initial conditions, after a certain transitional period, the filament aligns with the local fiber orientation. The alignment of the filament is determined by the directional variations in cell coupling due to fiber rotation and by boundary conditions. Our findings provide a mechanistic explanation for the prevalence of intramural reentry over transmural reentry during polymorphic ventricular tachycardia and fibrillation.     

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.     

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.

     

Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting.

Bed rest deconditioning leads to physiological cardiac atrophy, which may compromise left ventricular (LV) filling during orthostatic stress by reducing diastolic untwisting and suction. To test this hypothesis, myocardial-tagged magnetic resonance imaging (MRI) was performed, and maximal untwisting rates of the endocardium, midwall, and epicardium were calculated by Harmonic Phase Analysis (HARP) before and after -6 degrees head-down tilt bed rest for 18 days with (n = 14) and without exercise training (n = 10). LV mass and LV end-diastolic volume were measured using cine MRI. Exercise subjects cycled on a supine ergometer for 30 min, three times per day at 75% maximal heart rate (HR). After sedentary bed rest, there was a significant reduction in maximal untwisting rates of the midwall (-46.8 +/- 14.3 to -35.4 +/- 12.4 degrees /s; P = 0.04) where untwisting is most reliably measured, and to a lesser degree of certainty in the endocardium (-50.3 +/- 13.8 to -40.1 +/- 18.5 degrees /s; P = 0.09); the epicardium was unchanged. In contrast, when exercise was performed in bed, untwisting rates were enhanced at the endocardium (-48.4 +/- 20.8 to -72.3 +/- 22.3 degrees /ms; P = 0.05) and midwall (-39.2 +/- 12.2 to -59.0 +/- 19.6 degrees /s; P = 0.03). The differential response was significant between groups at the endocardium (interaction P = 0.02) and the midwall (interaction P = 0.004). LV mass decreased in the sedentary group (156.4 +/- 30.3 to 149.5 +/- 27.9 g; P = 0.07), but it increased slightly in the exercise-trained subjects (156.4 +/- 34.3 to 162.3 +/- 40.5 g; P = 0.16); (interaction P = 0.03). We conclude that diastolic untwisting is impaired following sedentary bed rest. However, exercise training in bed can prevent the physiological cardiac remodeling associated with bed rest and preserve or even enhance diastolic suction.     

Characterization of the normal cardiac myofiber field in goat measured with MR-diffusion tensor imaging

Cardiac myofiber orientation is a crucial determinant of the distribution of myocardial wall stress. Myofiber orientation is commonly quantified by helix and transverse angles. Accuracy of reported helix angles is limited. Reported transverse angle data are incomplete. We measured cardiac myofiber orientation postmortem in five healthy goat hearts using magnetic resonance-diffusion tensor imaging. A novel local wall-bound coordinate system was derived from the characteristics of the fiber field. The transmural course of the helix angle corresponded to data reported in literature. The mean midwall transverse angle ranged from -12 +/- 4 degrees near the apex to +9.0 +/- 4 degrees near the base of the left ventricle, which is in agreement with the course predicted by Rijcken et al. (18) using a uniform load hypothesis. The divergence of the myofiber field was computed, which is a measure for the extent to which wall stress is transmitted through the myofiber alone. It appeared to be <0.07 mm(-1) throughout the myocardial walls except for the fusion sites between the left and right ventricles and the insertion sites of the papillary muscles.     

Distribution of myocardial stress and its influence on coronary blood flow

The myocardial stress was analyzed by biomechanical modeling in correlation with experimental findings. The pressure-volume relationship follows the stress-strain relationship of muscle fibers. From the knowledge of fiber orientation and the distribution of sarcomere length, the myocardial stress components including fiber, longitudinal, circumferential and radial stresses were expressed as a function of fraction of wall thickness. The coronary blood flow is influenced by the myocardial radial stress. With the use of vascular waterfall theory, it is possible to correlate the theoretically defined stress distribution with experimentally obtained stress distribution. An elevation of radial stress in myocardium causes a reduction of vessel patency. During both systole and diastole, vessel patency remains constant at epicardium. At endocardium, however, vessel patency undergoes rhythmic changes following the systolic and diastolic influences of the radial stress. The physiological implication is that during systole, the endocardium suffers low blood flow and this transient ischemic state requires compensatory replenishment from diastolic perfusion. Such phenomena become less apparent toward the epicardium.     

Transmural left ventricular mechanics underlying torsional recoil during relaxation

Early relaxation in the cardiac cycle is characterized by rapid torsional recoil of the left ventricular (LV) wall. To elucidate the contribution of the transmural arrangement of the myofiber to relaxation, we determined the time course of three-dimensional fiber-sheet strains in the anterior wall of five adult mongrel dogs in vivo during early relaxation with biplane cineangiography (125 Hz) of implanted transmural markers. Fiber-sheet strains were found from transmural fiber and sheet orientations directly measured in the heart tissue. The strain time course was determined during early relaxation in the epicardial, midwall, and endocardial layers referenced to the end-diastolic configuration. During early relaxation, significant circumferential stretch, wall thinning, and in-plane and transverse shear were observed (P < 0.05). We also observed significant stretch along myofibers in the epicardial layers and sheet shortening and shear in the endocardial layers (P < 0.01). Importantly, predominant epicardial stretch along the fiber direction and endocardial sheet shortening occurred during isovolumic relaxation (P < 0.05). We conclude that the LV mechanics during early relaxation involves substantial deformation of fiber and sheet structures with significant transmural heterogeneity. Predominant epicardial stretch along myofibers during isovolumic relaxation appears to drive global torsional recoil to aid early diastolic filling.     

Ventricular pacing-induced loss of contractile function and development of epicardial inflammation

Perturbations in the normal sequence of ventricular activation can create regions of early and late activation, leading to dysynchronous contraction and areas of dyskinesis. Dyskinesis occurs across the left ventricular (LV) wall, and its presence may have important consequences on cardiac structure and function in normal and failing hearts. Acutely, dyskinesis can trigger inflammation and, in the long term (6 wk and above), leads to LV remodeling. The mechanisms that trigger these changes are unknown. To gain further insight, we used a canine model to evaluate transumural changes in myocardial function and inflammation induced by epicardial LV pacing. The results indicate that 4 h of LV suprathreshold pacing resulted in a 30% local loss of endocardial thickening. Assessment of neutrophil infiltration showed a significant approximately fivefold increase in myeloperoxidase activity in the epicardium versus the midwall/endocardium. Matrix metalloproteinase-9 activity increased ～2 fold in the epicardium and ROS generation increased ～2.5-fold compared with the midwall/endocardium. To determine the effects that electrical current alone has on these end points, a group of animals was subjected to subthreshold pacing. Significant increases were observed only in epicardial myeloperoxidase levels. Thus, the results indicate that transmural dyskinesis induced by suprathreshold epicardial LV activation triggers a localized epicardial inflammatory response, whereas subthreshold stimulation appears to solely induce the trapping of leucocytes. Suprathreshold pacing also induces a loss of endocardial function. These results may have important implications as to the nature of the mechanisms that trigger the inflammatory response and possibly long-term remodeling in the setting of dysynchrony.     

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.     

Passive diastolic modelling of human ventricles: Effects of base movement and geometrical heterogeneity

Left-ventricular (LV) remodelling, associated with diastolic heart failure, is driven by an increase in myocardial stress. Therefore, normalisation of LV wall stress is the cornerstone of many therapeutic treatments. However, information regarding such regional stress–strain for human LV is still limited. Thus, the objectives of our study were to determine local diastolic stress–strain field in healthy LVs, and consequently, to identify the regional variations amongst them due to geometric heterogeneity. Effects of LV base movement on diastolic model predictions, which were ignored in the literature, were further explored. Personalised finite-element modelling of five normal human bi-ventricles was carried out using subject-specific myocardium properties. Model prediction was validated individually through comparison with end-diastolic volume and a new shape-volume based measurement of LV cavity, extracted from magnetic resonance imaging. Results indicated that incorporation of LV base movement improved the model predictions (shape-volume relevancy of LV cavity), and therefore, it should be considered in future studies. The LV endocardium always experienced higher fibre stress compared to the epicardium for all five subjects. The LV wall near base experienced higher stress compared to equatorial and apical locations. The lateral LV wall underwent greater stress distribution (fibre and sheet stress) compared to other three regions. In addition, normal ranges of different stress–strain components in different regions of LV wall were reported for five healthy ventricles. This information could be used as targets for future computational studies to optimise diastolic heart failure treatments or design new therapeutic interventions/devices.     

Influence of left-ventricular shape on passive filling properties and end-diastolic fiber stress and strain

Passive filling is a major determinant for the pump performance of the left ventricle and is determined by the filling pressure and the ventricular compliance. In the quantification of the passive mechanical behaviour of the left ventricle and its compliance, focus has been mainly on fiber orientation and constitutive parameters. Although it has been shown that the left-ventricular shape plays an important role in cardiac (patho-)physiology, the dependency on left-ventricular shape has never been studied in detail. Therefore, we have quantified the influence of left-ventricular shape on the overall compliance and the intramyocardial distribution of passive fiber stress and strain during the passive filling period. Hereto, fiber stress and strain were calculated in a finite element analysis of passive inflation of left ventricles with different shapes, ranging from an elongated ellipsoid to a sphere, but keeping the initial cavity volume constant. For each shape, the wall volume was varied to obtain ventricles with different wall thickness. The passive myocardium was described by an incompressible hyperelastic material law with transverse isotropic symmetry along the muscle fiber directions. A realistic transmural distribution in fiber orientation was assumed. We found that compliance was not altered substantially, but the transmural distribution of both passive fiber stress and strain was highly dependent on regional wall curvature and thickness. A low curvature wall was characterized by a maximum in the transmural fiber stress and strain in the mid-wall region, while a steep subendocardial transmural gradient was present in a high curvature wall. The transmural fiber stress and strain gradients in a low and high curvature wall were, respectively, flattened and steepened by an increase in wall thickness.     

Some implications of a constant fiber stress hypothesis in the diastolic left ventricle

A thick-wall incompressible, elastic sphere was used as a model for the diastolic rat left ventricle. A model for myocardial nonhomogeneity was derived assuming that fiber (circumferential) stress was independent of position in the ventricular wall. The theoretical implications of the resulting constitutive relations together with the spherical model were analyzed in the context of large deformation elasticity theory. It was found that muscle stiffness at a given level of uniaxial stress increased monotonically from the endocardium to the epicardium. In addition, fiber stress was found to be essentially a linear function of transmural pressure above a pressure of 6 g/cm². It was also shown theoretically that neglecting the nonhomogeneity of the myocardium resulted in a state of stress which differed significantly from that predicted by the nonhomogeneous model. For example, at a transmural pressure of 14 g/cm², fiber stress in the nonhomogenous model was equal to 17 g/cm² while fiber stress in the homogeneous model varied between 100 g/cm² at the endocardial surface and 2 g/cm² at the epicardial surface. The change in muscle stiffness with position which characterized the nonhomogeneous model also tended to linearize the highly curvilinear radial stress distribution predicted by the homogeneous model at a given transmural pressure.     

Transmural cardiac strains in the lateral wall of the ovine left ventricle

The constant-volume property of contracting cardiac muscle has been invoked in models of heart wall mechanics that predict that systolic subendocardial left ventricular (LV) wall thickening must significantly exceed subepicardial thickening. To examine this prediction, we implanted arrays of radiopaque markers to measure lateral equatorial wall transmural strains and global and regional LV geometry in seven sheep and studied the four-dimensional dynamics of these arrays using biplane videofluoroscopy (60 Hz) in anesthetized intact animals 1 and 8 wk after surgery. A transmural gradient of systolic lateral wall thickening was observed at 1 wk (P = 0.009; linear regression) but was no longer present at 8 wk (P = 0.243). Referenced to end diastole, group mean (+/-SD) end-systolic radial subepicardial, midwall, and subendocardial wall thickening strains were, respectively, 0.08 +/- 0.08, 0.14 +/- 0.08, and 0.22 +/- 0.12 at 1 wk and 0.19 +/- 0.07 (P = 0.02; 1 vs. 8 wk), 0.20 +/- 0.04, and 0.23 +/- 0.07 at 8 wk. With the exception of an 8-ml (7%) increase in end-diastolic volume (P = 0.04) from 1 to 8 wk, LV shape and hemodynamics were otherwise unchanged. We conclude that equivalent hemodynamics can be generated by the left ventricle with or without a transmural gradient of systolic wall thickening in this region; thus such a gradient is unlikely to be a fundamental property of the contracting LV myocardium. We discuss some implications of these findings regarding mechanisms involved in systolic wall thickening.     

Transmural reentry triggered by epicardial stimulation during acute ischemia in canine ventricular muscle

Ischemia depresses tissue excitability more rapidly in the ventricular epicardium than in the endocardium. We hypothesized that this would provide the substrate for transmural reentry originating in the epicardium. We mapped transmural conduction in isolated and perfused wedges taken from canine left ventricles during global ischemia while pacing alternately between the epicardium and endocardium. Ischemia reduced conduction velocity more in the epicardium than in the endocardium. We observed that the epicardial-initiated activation penetrated the ventricular wall transmurally while failing to conduct laterally along the epicardium, then conducted laterally along the endocardium and midmyocardium, and reentered the epicardium in 9 of 16 wedges during epicardial stimulation after 600 +/- 182 s of ischemia. Endocardial stimulation applied immediately before or after the epicardial stimulation initiated activation that spread quickly along the endocardium and then transmurally to the epicardium without reentry in six of the nine wedges. The transmural asymmetric conduction was not observed in four separate wedges after the endocardium was removed. Therefore, ischemia-induced transmural gradient of excitability provided the substrate for reentry during epicardial stimulation.