Statistical analysis of the angle of intrusion of porcine ventricular myocytes from epicardium to endocardium using diffusion tensor magnetic resonance imaging.

Pairs of cylindrical knives were used to punch semicircular slices from the left basal, sub-basal, equatorial, and apical ventricular wall of porcine hearts. The sections extended from the epicardium to the endocardium. Their semicircular shape compensated for the depth-related changing orientation of the myocytes relative to the equatorial plane. The slices were analyzed by diffusion tensor magnetic resonance imaging. The primary eigenvector of the diffusion tensor was determined in each pixel to calculate the number and angle of intrusion of the long axis of the aggregated myocytes relative to the epicardial surface. Arrays of axially sectioned aggregates were found in which 53% of the approximately two million segments evaluated intruded up to +/-15 degrees , 40% exhibited an angle of intrusion between +/-15 degrees and +/-45 degrees , and 7% exceeded an angle of +/-45 degrees , the positive sign thereby denoting an epi- to endocardial spiral in clockwise direction seen from the apex, while a negative sign denotes an anticlockwise spiral from the epicardium to the endocardium. In the basal and apical slices, the greater number of segments intruded in positive direction, while in the sub-basal and equatorial slices, negative angles of intrusion prevailed. The sampling of the primary eigenvectors was insensitive to postmortem decomposition of the tissue. In a previous histological study, we also documented the presence of large numbers of myocytes aggregated with their long axis intruding obliquely from the epicardial to the endocardial ventricular surfaces. We used magnetic resonance diffusion tensor imaging in this study to provide a comprehensive statistical analysis.

Beta-blockade at low doses restoring the physiological balance in myocytic antagonism.

OBJECTIVE: The ventricular mass is organized in the form of meshwork, with populations of myocytes aggregated in a supporting matrix of fibrous tissue, with some myocytes aligned obliquely across the wall so as to work in an antagonistic fashion compared to the majority of myocytes, which are aggregated together in tangential alignment. Prompted by results from animal experiments, which showed a disparate response of the two populations of aggregated myocytes to negative inotropic medication, we sought to establish whether those myocytes that aggregated so as to extend obliquely across the thickness of the ventricular walls are more sensitive to beta-blockade than the prevailing population in which the myocytes are aggregated together with tangential alignment. If the two populations respond in similar differing fashion in the clinical situation, we hypothesize that this might help to explain why drugs blocking the beta-receptors improve function of the ventricular pump in the setting of congestive cardiac failure. METHODS: We implanted needle probes in 13 patients studied during open heart surgery, measuring the forces generated in the ventricular wall and seeking to couple the probes either to myocytes aggregated together with tangential alignment or to those aggregated in oblique fashion across the ventricular walls. In a first series of patients, we injected probatory doses intravenously, amounting to a total bolus of 40-100mg Esmolol, while in a second series, we gave fixed yet rising doses of 5, 10, and 20mg Esmolol in three separate boluses. RESULTS: Forces recorded in the aggregated myocytes with tangential alignment decreased insignificantly upon administration of low doses (57.1+/-12.4 mN-->56.6+/-7.6 mN), while forces recorded in the myocytes aggregated obliquely across the ventricular wall showed a significant decrease in the mean (59.3+/-11.6 mN-->47.4+/-6.4 mN). CONCLUSIONS: The markedly disparate action of drugs blocking beta-receptors at low dosage seems to be related to the heterogeneous extent, and time course, of systolic loading of the myocytes. This, in turn, depends on whether the myocytes themselves are aggregated together with tangential or oblique alignments relative to the thickness of the ventricular walls.

An analysis of the spatial arrangement of the myocardial aggregates making up the wall of the left ventricle.

OBJECTIVE: We used the technique of peeling of myocardial aggregates, usually described as 'fibres', to determine the spatial arrangement of the myocytes in the left ventricular wall of a healthy autopsied human heart. METHODS: We digitised the left ventricular outer and inner boundaries, as well as the pathways in space, of almost 3000 aggregates harvested from the left ventricular myocardium. During the process of gradual peeling, we sought to identify the myocardial aggregates as uniformly as possible. Despite this, interpolation was necessary to complete the pattern so as to construct a unit vector field that represented the preferred direction of the myocardial aggregates throughout the entirety of the walls of the left ventricle of this individual human heart. RESULTS: Apart from the overall systematic arrangement of the aggregates necessary to achieve physiologic ventricular contraction, we documented substantial local heterogeneities in the orientation of the myocardial aggregates. In particular, a significant proportion of aggregates was found to intrude obliquely with respect to the ventricular boundaries, with markedly heterogeneous distribution. Moreover, the distribution of the helical angle of the aggregates relative to the ventricular base varied notably throughout the left ventricular free walls and the septum. Within the generally quite uniform and continuous structure of the ventricular mass, we were, however, unable to identify any organised tracts or functional subunits such as a 'helical ventricular band', nor did we find radial fibrous lamellas coursing across the ventricular wall. CONCLUSION: We suggest that the impact of local anatomical inhomogeneities, associated with gradients in regional contractile function on global ventricular dynamics, has been systematically underestimated in the past. Our analysis confirms furthermore the continuous nature of the myocardium associated with an overall gross organisation of the fibre direction field; however, there is no evidence of substructures compartmentalising the ventricles.

Three-dimensional architecture of the left ventricular myocardium.

Concepts for ventricular function tend to assume that the majority of the myocardial cells are aligned with their long axes parallel to the epicardial ventricular surface. We aimed to validate the existence of aggregates of myocardial cells orientated with their long axis intruding obliquely between the ventricular epicardial and endocardial surfaces and to quantitate their amount and angulation. To compensate for the changing angle of the long axis of the myocytes relative to the equatorial plane of the ventricles with varying depths within the ventricular walls, the so-called helical angle, we used pairs of cylindrical knives of different diameters to punch semicircular slices from the left ventricular wall of pigs, the slices extending from the epicardium to the endocardium. The slices were pinned flat, fixed in formaldehyde, embedded in paraffin, sectioned, stained with azan or hematoxilin and eosin, and analyzed by a new semiautomatic procedure. We made use of new techniques in informatics to determine the number and angulation of the aggregates of myocardial cells cut in their long axis. The alignment of the myocytes cut longitudinally varied markedly between the epicardium and the endocardium. Populations of myocytes, arranged in strands, diverge by varying angles from the epicardial surface. When paired knives of decreasing diameter were used to cut the slices, the inclination of the diagonal created by the arrays increases, while the lengths of the array of cells cut axially decreases. The visualization of the size, shape, and alignment of the myocytic arrays at any side of the ventricular wall is determined by the radius of the knives used, the range of helical angles subtended by the alignment of the myocytes throughout the thickness of the wall, and their angulation relative to the epicardial surface. Far from the majority of the ventricular myocytes being aligned at angles more or less tangential to the epicardial lining, we found that three-fifths of the myocardial cells had their long axes diverging at angles between 7.5 and 37.5 degrees from an alignment parallel to the epicardium. This arrangement, with the individual myocytes supported by connective tissue, might control the cyclic rearrangement of the myocardial fibers. This could serve as an important control of both ventricular mural thickening and intracavitary shape.

The myocardium and its fibrous matrix working in concert as a spatially netted mesh: a critical review of the purported tertiary structure of the ventricular mass.

With the increasing interest now paid to volume reduction surgery, in which the cardiac surgeon is required to resect the ventricular myocardium to an extent unenvisaged in the previous century, it is imperative that we develop as precise knowledge as is possible of the basic structure of the ventricular myocardial mass and its functional correlates. This is the most important in the light of the adoption by some cardiac surgeons of an unvalidated model which hypothesises that the entire myocardial mass can be unravelled to produce one continuous band. It is our opinion that this model, and the phylogenetic and functional correlates derived from it, is incompatible with current concepts of cardiac structure and cardiodynamics. Furthermore, the proponents of the continuous myocardial band have made no effort to demonstrate perceived deficiencies with current concepts, nor have they performed any histological studies to validate their model. Clinical results using modifications of radius reduction surgery based on the concept of the continuous myocardial band show that the procedure essentially becomes ineffective. As we show in this review, if we understand the situation correctly, it was the erstwhile intention of the promoters of the continuous band to elucidate the basic mechanism of diastolic ventricular dilation. Their attempts, however, are doomed to failure, as is any attempt to conceptualise the myocardial mass on the basis of a tertiary structure, because of the underlying three-dimensional netting of the myocardial aggregates and the supporting fibrous tissue to form the myocardial syncytium. Thus, the ventricular myocardium is arranged in the form of a modified blood vessel rather than a skeletal muscle. If an analogy is required with skeletal muscle, then the ventricular myocardium possesses the freedom of motion, and the ability for shaping and conformational self-controlling that is better seen in the tongue. It is part of this ability that contributes to the rapid end-systolic ventricular dilation. Histologic investigations reveal that the fibrous content of the three-dimensional mesh is relatively inhomogeneous through the ventricular walls, particularly when the myocardium is diseased. The regional capacity to control systolic mural thickening, therefore, varies throughout the walls of the ventricular components. The existence of the spatially netted structure of the ventricular mass, therefore, must invalidate any attempt to conceptualise the ventricular myocardium as a tertiary arrangement of individual myocardial bands or tracts.

Ventricular myocardial architecture as visualised in postmortem swine hearts using magnetic resonance diffusion tensor imaging.

OBJECTIVE: The three-dimensional arrangement of the ventricular myocardial architecture remains controversial, in part because histological assessment is difficult to achieve, while anatomic dissections are, of necessity, destructive. In this study, we describe how the use of magnetic resonance diffusion tensor imaging has permitted us to reconstruct with precision the architecture of the ventricular myocardial fibres in the post-mortem swine heart. METHODS AND RESULTS: We obtained diffusion-weighted spin-echo measurements of autopsied porcine hearts using a whole body MR system. We calculated the diffusion tensor and the corresponding eigenvectors on a voxel-by-voxel basis. This permitted us to colour code the fibres, and reconstruct them by connecting voxels in direction of the largest eigenvector. Such reconstructions show that, in the middle layer of the left ventricle, most of the fibres have a circular orientation, albeit that a far from negligible component runs in a transverse direction. With increasing distance from the epicardium, the orientation of the fibres shows a continuous change in angulation with respect to an axis normal to the epicardium. CONCLUSION: Our data presented here supports the concept that the ventricular mass is arranged as a complex three-dimensional mesh of tangential and intruding fibres. The data offers no support for the concept of a "unique myocardial band". The method has the potential to detecting deviations from this basic normal architecture, being capable of reconstructing the ventricular mass so as to assess the spatial coordinates of any single fibre strand. The technique, therefore, has major potential clinical applications in the setting of the failing or malformed heart, potentially being able to identify either systematic or regional disarray of the myocardial fibres.

The relationship between structure and function: why does reshaping the left ventricle surgically not always result in functional improvement?

Surgical strategies recently introduced to improve ventricular function have been based on the concepts of reduction of ventricular diameter, synchronization of myocardial activity, passive support of diastolic ventricular shape, and active support of systolic ventricular constriction. They have depended on several established theoretical assumptions, not all of which are totally valid. Clinical results have proved markedly variable. This is especially true for procedures designed to reduce the radius of the left ventricle. Some have reported up to 80% mortality, whereas others achieve results comparable with those for heart transplantation. Because of this, the method runs the risk to be rejected, or else, its more widespread application will be postponed until essential details concerning the basic concepts have been elucidated. It is these details which we discuss in this review.