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 ventricle

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 tract

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±12.4mN→56.6±7.6mN), while forces recorded in the myocytes aggregated obliquely across the ventricular wall showed a significant decrease in the mean (59.3±11.6mN→47.4±6.4mN). 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 wall

Laughter is in the air: Involvement of key nodes of the emotional motor system in the anticipation of tickling

In analogy to the appreciation of humor, that of tickling is based upon the re- interpretation of an anticipated emotional situation. Hence, the anticipation of tickling contributes to the final outburst of ticklish laughter. To localize the neuronal substrates of this process, fMRI was conducted on 31 healthy volunteers. The state of anticipation was simulated by generating an uncertainty respecting the onset of manual foot tickling. Anticipation was characterized by an augmented fMRI- signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area, as well as by an attenuated one in the internal globus pallidus. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling. These findings are consistent with an encoding of the expected emotional consequences of tickling and suggest that early regulatory mechanisms influence, automatically, the laughter circuitry at the level of affective and sensory processing. Tickling activated not only those regions of the brain that were involved during anticipation, but also the posterior insula, the anterior cingulate cortex and the periaqueductal gray matter. Sequential or combined anticipatory and tickling-related neuronal activities may adjust emotional- and sensorimotor pathways in preparation for the impending laughter response

Spectral features of nuclear DNA in human sperm assessed by Raman Microspectroscopy: Effects of UV-irradiation and hydration

Raman Microspectroscopy represents an innovative tool for the assessment of sperm biochemical features otherwise undetectable by routine semen analysis. Previously, it was shown that induced DNA damage can be detected in smeared sperm by this technique. This novel readout may be of value for clinical settings especially if it can be transferred to living cells. Yet, starting with living sperms this study was carried-out using a variety of conditions to disclose the Raman features of sperm nuclei under different hydration conditions and UV exposure. Human sperm were immobilized and Raman spectra were obtained from individual sperm as repeated measurements. To create conditions with controlled DNA damage, sperm samples were exposed to ultraviolet light. Several media were used to evaluate their effect on Raman spectra in aqueous conditions. To substantiate differences between the experimental conditions, the spectra were analyzed by Principal Component Analysis. We observed that spectra of sperm nuclei obtained in different solutions showed a qualitatively unchanged spectral pattern showing the principal signals related to DNA. Evaluating the effect of ultraviolet light generated the finding that spectra representing DNA damage were only observed in dry conditions but not in aqueous medium. Thus, Raman microspectroscopy was successfully applied for sperm analysis in different conditions, among them in live spermatozoa in aqueous solution during the initial measurement, revealing the principle use of this technique. However, implementation of Raman spectroscopy as a technique for clinical sperm analysis and selection may be especially relevant when DNA evaluation can be established using live sperm

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 ventricle