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

In an attempt to provide a better understanding of our finding that regions with contracting left ventricular myofibers need not develop a significant transmural systolic wall thickening gradient, the analytic approach of Costa et al. was applied to the four-dimensional dynamic data obtained 1 and 8 wk after surgical implantation of transmural radiopaque beads in the lateral equatorial left ventricular wall in seven ovine hearts. Quantitative histology of tissue blocks demonstrated that fiber angles varied linearly across the wall in this region from -37 degrees in the subepicardium to +18 degrees in the subendocardium. Sheet angles exhibited a pleated-sheet behavior, alternating sign from subepicardium to subendocardium. From end diastole (reference configuration) to end systole (deformed configuration), fiber strain was uniformly negative, sheet extension and sheet thickening were uniformly positive, and sheet-normal shear contributed to wall thickening at all wall depths. Subepicardial radial wall thickening increased significantly from week 1 to week 8, with significant increases in the contributions from subepicardial sheet extension and sheet-normal shear. At 1 and 8 wk, the contribution of sheet-normal shear to wall thickening was substantial at all transmural depths; the contribution of sheet extension to wall thickening was greatest in the subepicardium and least in the subendocardium, and the contribution of sheet thickening to wall thickening was greatest in the subendocardium and least in the subepicardium. A mechanistic model is proposed that provides a working hypothesis that a selective decrease in subepicardial intercellular matrix stiffness is responsible for elimination of the transmural wall thickening gradient 1-8 wk after marker implantation surgery.     

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.     

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.     

Theoretical models in mechanics of the left ventricle

Different rheological concepts and theoretical studies have been recently presented using models of myocardial mechanics. Complex analysis of the mechanical behavior of the left ventricular wall have been developed in order to estimate the local stresses and deformations that occur during the heart cycle as well as the ventricular stroke volume and pressure. Theoretical models have taken into account non-linear and viscoelastic passive properties of the myocardium tissue, when subjected to large deformations, through given strain energy functions or stress-strain relations. Different prolate spheroid geometries have been considered for such thick shell cardiac structure. During the active state of the contraction, the rheological behavior of the fibers has been described using different muscle models and relationships between fiber tension and strain, and activation degree. A forthcoming approach for bridging the gap between the knowledge of the muscle fiber microrheological properties and the study of the mechanical behavior of the entire ventricle, consists in including anisotropic and inhomogeneous effects through fiber direction field.     

Electrotonic cancellation of transmural electrical gradients in the left ventricle in man

Myocardial cells isolated from different depths of the ventricular wall show substantial differences in action potential duration. Whether these electrophysiological differences are present in vivo when the cells are well coupled is a subject of ongoing controversy. This article provides a brief review and includes experimental evidence derived from patients undergoing cardiac surgery.     

Electromechanical coupling in cardiomyocytes from transmural layers of guinea pig left ventricle

The electrical and mechanical activity of heart ventricle cardiomyocytes is known to vary depending on the spatial location of cells in the wall, in particular, transmurally from the sub-endocardial layer to the sub-epicardial one. To investigate intracellular mechanisms of the functional heterogeneity of cardiomyocytes we developed mathematical models of the electromechanical coupling in cardiomyocytes from different transmural layers across the left ventricle (LV) wall of guinea pig. It is shown that the mechanisms of both direct linkages and feedback in the electromechanical coupling contribute to differences in both the shape and duration of action potential, and speed characteristics of contraction between isolated cardiac myocytes from the sub-endocardial and sub-epicardial layers.     

Contribution of laminar myofiber architecture to load-dependent changes in mechanics of LV myocardium

The ventricular myocardium consists of a syncytium of myocytes organized into branching, transmurally oriented laminar sheets approximately four cells thick. When systolic deformation is expressed in an axis system determined by the anatomy of the laminar architecture, laminar sheets of myocytes shear and laterally extend in an approximately radial direction. These deformations account for ~90% of normal systolic wall thickening in the left ventricular free wall. In the present study, we investigated whether the changes in systolic and diastolic function of the sheets were sensitive to alterations in systolic and diastolic load. Our results indicate that there is substantial reorientation of the laminar architecture during systole and diastole. Moreover, this reorientation is both site and load dependent. Thus as end-diastolic pressure is increased and the left ventricular wall thins, sheets shorten and rotate away from the radial direction due to transverse shearing, opposite of what occurs in systole. Both mechanisms of thickening contribute substantially to normal left ventricular wall function. Whereas the relative contributions of shear and extension are comparable at the base, sheet shear is the predominant factor at the apex. The magnitude of shortening/extension and shear increases with preload and decreases with afterload. These findings underscore the essential contribution of the laminar myocardial architecture for normal ventricular function throughout the cardiac cycle.     

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.     

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.     

Dynamics of the strength of the rat left ventricle wall in experimental uncomplicated myocardial infarction

Left ventricular wall stability was studied in 131 normal rats at different terms of uncomplicated experimental myocardial infarction. Left ventricular wall stability was estimated by the normal effort required for its destruction. Normal left ventricular wall could stand the pressure of 1.1 X 10(5) Pa. During ischemic phase of myocardial infarction the wall stability in the infarction area increased up to 1.5 X 10(5) Pa. It diminished during necrotic phase, however timely started repair processes did not let it drop lower than 1.0 X 10(5) Pa. The mechanisms of preserving ventricular wall stability in the infarction area were studied in detail.     

Contraction wave in axial direction in free wall of guinea pig left ventricle

Mechanical activation of the normal left ventricle (LV) is not simultaneous; however, the potential consequences of the ejection function of the ventricle are not entirely known. We studied contraction of the LV free wall to determine whether it reveals a contraction wave in the axial direction during ejection. Seven guinea pig hearts in situ were studied via thoracotomy. In each heart, the ventricular and aortic pressures were measured by two microtipped manometers (2-Fr, Millar). Contraction of the LV free wall was assessed with a video system (Dalsa D6-0256 camera and EPIX PIXCI D32 frame grabber; acquisition rate, 500 frames/s), and 15-18 epicardial markers were used to divide the region into 20-25 triangular areas. The area sizes were studied during contraction to locate the position of the contraction wave. For each triangular area, two variables were determined as follows: the time (t(c)) from the end of diastole until the size of the area reached 80% of maximum size reduction (normalized with the duration of systole) and the normalized latitude (L(ax)) of the area (determined at the end of diastole). A relationship between these two variables was determined by regression analysis. We found that the t(c) at which the contraction wave reached a triangular area was in positive correlation with the L(ax) value for that triangular area with a slope of 0.25 +/- 0.09 and a linear correlation coefficient of 0.41 +/- 0.08. Thus contraction in the guinea pig LV free wall occurs progressively from apex to base with successive areas reaching 80% contraction.     

Functional and anatomical variability of canine cardiac sympathetic efferent pathways: implications for regional denervation of the left ventricle

To further elucidate the functional anatomy of canine cardiac innervation as well as to assess the feasibility of producing regional left ventricular sympathetic denervation, the chronotropic and (or) regional left ventricular inotropic responses produced by stellate or middle cervical ganglion stimulation were investigated in 22 dogs before and after sectioning of individual major cardiopulmonary or cardiac nerves. Sectioning the right or left subclavian ansae abolished all cardiac responses produced by ipsilateral stellate ganglion stimulation. Sectioning a major sympathetic cardiopulmonary nerve, other than the right interganglionic nerve, usually reduced, but seldom abolished, regional inotropic responses elicited by ipsilateral middle cervical ganglion stimulation. Sectioning the dorsal mediastinal cardiac nerves consistently abolished the left ventricular inotropic responses elicited by right middle cervical ganglion stimulation but minimally affected those elicited by left middle cervical ganglion stimulation. In contrast, cutting the left lateral cardiac nerve decreased the inotropic responses in lateral and posterior left ventricular segments elicited by left middle cervical ganglion stimulation but had little effect on the inotropic responses produced by right middle cervical ganglion stimulation. In addition, the ventral mediastinal cardiac nerve was found to be a significant sympathetic efferent pathway from the left-sided ganglia to the left ventricle. These results indicate that the stellate ganglia project axons to the heart via the subclavian ansae and thus effective sympathetic decentralization can be produced by cutting the subclavian ansae; the right-sided cardiac sympathetic efferent innervation of the left ventricle converges intrapericardially in the dorsal mediastinal cardiac nerves; and the left-sided cardiac sympathetic efferent innervation of the left ventricle diverges to innervate the left ventricle by a number of nerves including the dorsal mediastinal, ventral mediastinal, and left lateral cardiac nerves. Thus consistent denervation of a region of the left ventricle can not be accomplished by sectioning an individual cardiopulmonary or cardiac nerve because of the functional and anatomical variability of the neural components in each nerve, as well as the fact that overlapping regions of the left ventricle are innervated by these different nerves.