[The antagonistic function of the heart muscle sustains the autoregulation according to Frank and Starling : Part I: Structure and function of heart muscle]. / Die antagonistische Funktion des Herzmuskels unterstützt die Autoregulation nach Frank-Starling : Teil I: Struktur und Funktion des Herzmuskels.

In the tradition of Harvey and according to Otto Frank the heart muscle structure is arranged in a strictly tangential fashion hence all contractile forces act in the direction of ventricular ejection. In contrast, morphology confirms that the heart consists of a 3-dimensional network of muscle fibers with up to two fifths of the chains of aggregated myocytes deviating from a tangential alignment at variable angles. Accordingly, the myocardial systolic forces contain, in addition to a constrictive also a (albeit smaller) radially acting component. Using needle force probes we have correspondingly measured an unloading type of force in a tangential direction and an auxotonic type in dilatative transversal direction of the ventricular walls to show that the myocardial body contracts actively in a 3-dimensional pattern. This antagonism supports the autoregulation of heart muscle function according to Frank and Starling, preserving ventricular shape, enhances late systolic fast dilation and attenuates systolic constriction of the ventricle wall. Auxotonic dilating forces are particularly sensitive to inotropic medication. Low dose beta-blocker is able to attenuate the antagonistic activity. All myocardial components act against four components of afterload, the hemodynamic, the myostructural, the stromatogenic and the hydraulic component. This complex interplay critically complicates clinical diagnostics. Clinical implications are far-reaching (see Part II, https://doi.org/10.1007/s00059-018-4735-x).

[Antagonistic function of the heart muscle : Part II: Clinical implications]. / Die antagonistische Funktion des Herzmuskels : Teil II: Klinische Auswirkungen.

In the hypertrophic heart the myostructural afterload in the form of endoepicardial networks is predominant, which enhances myocardial hypertrophy. The intrinsic antagonism is derailed. Likewise, the connective tissue scaffold, i.e. the stromatogenic afterload, is enriched in the response to the derailment of antagonism in a hypertrophic heart up to regional captivation of the heart musculature. Due to the selective susceptibility of the auxotonic, contracting oblique transmural myocardial network for low dose negative inotropic medication, this promises to attenuate progress in myocardial hypertrophy. Volume reduction surgery is most effective in reducing wall stress as long as the myocardium is not critically fettered by fibrosis. The use of external mechanical circulatory support is then effective if the heart is supported in its resting mode, which means around a middle width and at minimal amplitude of motion. The takotsubo cardiomyopathy might possibly reflect an isolated, extreme stimulation of the intrinsic antagonism as a response to hormonally induced sensitization of the myocardium to catecholamine. A particular significant conclusion with respect to the diseased heart is that clinical diagnostics need new impulses with a focus on the analysis of local motion patterns and on myocardial stiffness reflecting disease-dependent antagonistic intensity. This would become a relevant diagnostic marker if corresponding (noninvasive) measurement techniques would become available.

Diastolic ventricular aspiration: a mechanism supporting the rapid filling phase of the human ventricles.

During the rapid filling phase of the heart cycle, the internal volumes of the two ventricular cavities approximately double, while the intraventricular pressures rise typically only by an amount of less than 1 kPa. Such a small pressure increase cannot be the sole driving mechanism for the large inflow of blood associated with ventricular expansion during this period. Instead, the rapid filling phase is to be interpreted as being mediated primarily by the heart recoiling elastically from its contracted state, causing blood to be aspirated rapidly into the ventricles. In order to study the role of this mechanism, elastic finite element (FE) simulations of ventricular expansion were performed, taking into account the large deformations occurring during this period and the effective compressibility of the myocardium due to intramural fluid flow. Thereby, a realistic three-dimensional geometry derived from magnetic resonance imaging (MRI) measurements of both human ventricles was used. To validate our FE analyses, the results were compared with published measurements relating to the rapid filling phase of the human left ventricle. Our study shows that, under normal physiological conditions, ventricular aspiration plays a key role in the ventricular filling process.

A finite element model of the human left ventricular systole.

Local wall stress is the pivotal determinant of the heart muscle's systolic function. Under in vivo conditions, however, such stresses cannot be measured systematically and quantitatively. In contrast, imaging techniques based on magnetic resonance (MR) allow the determination of the deformation pattern of the left ventricle (LV) in vivo with high accuracy. The question arises to what extent deformation measurements are significant and might provide a possibility for future diagnostic purposes. The contractile forces cause deformation of LV myocardial tissue in terms of wall thickening, longitudinal shortening, twisting rotation and radial constriction. The myocardium is thereby understood to act as a densely interlaced mesh. Yet, whole cycle image sequences display a distribution of wall strains as function of space and time heralding a significant amount of inhomogeneity even under healthy conditions. We made similar observations previously by direct measurement of local contractile activity. The major reasons for these inhomogeneities derive from regional deviations of the ventricular walls from an ideal spheroidal shape along with marked disparities in focal fibre orientation. In response to a lack of diagnostic tools able to measure wall stress in clinical routine, this communication is aimed at an analysis and functional interpretation of the deformation pattern of an exemplary human heart at end-systole. To this end, the finite element (FE) method was used to simulate the three-dimensional deformations of the left ventricular myocardium due to contractile fibre forces at end-systole. The anisotropy associated with the fibre structure of the myocardial tissue was included in the form of a fibre orientation vector field which was reconstructed from the measured fibre trajectories in a post mortem human heart. Contraction was modelled by an additive second Piola-Kirchhoff active stress tensor. As a first conclusion, it became evident that longitudinal fibre forces, cross-fibre forces and shear along with systolic fibre rearrangement have to be taken into account for a useful modelling of systolic deformation. Second, a realistic geometry and fibre architecture lead to typical and substantially inhomogeneous deformation patterns as they are recorded in real hearts. We therefore, expect that the measurement of systolic deformation might provide useful diagnostic information.

Architecture of the myocardium in computed tomography.

To determine whether current concepts of myocardial organization were in fact the result of artifacts introduced by the dissection technique, a method comprising air injection of the coronary arteries (which gently separated the myocardial fibers) and computerized tomography was devised. Viewing the tomographs cinematographically confirmed the concept that the heart is formed by a double looping of myocardial fiber bands was correct. Examination of abnormal hearts, eg, one with Duchenne muscular dystrophy, shows that pathologic tissue disarrangements could also be identified.

Late ventricular structure after partial left ventriculectomy.

Nine months after partial ventriculectomy, a 53-year-old man died of progressive heart failure. His heart was examined to determine the alignment of the muscle fibers around the ventricular scar, which was 11 cm long, 1.3 cm thick and 4 cm wide. The scar reached 2 to 12 mm beyond the surgical suture line. The fibers in the middle and subendocardial layers were malaligned, resulting in convergence, compression and regional necrosis.

Thiouracil-induced myocardial fibrosis.

Rabbits were fed with thiouracil for 8 months. Subsequently their hearts were examined electron microscopically as well as biochemically for collagen and hexosamine content. Chronic treatment with thiouracil induced an increase in interstitial connective tissue collagen and hexosamine without visible necrosis. As seen by electron microscopy, the increase in collagen content might have been caused by stimulation of the fibrocytes. Furthermore, the heart muscle cells showed deep indentations and bulges of the cell membrane and an enlargement of the T-system.

Distribution of alkaline phosphatase in the microcirculatory pathways of the coronary system.

By histochemistry alkaline-phosphatase-activity in the microcirculatory pathways of the coronary vascular system were investigated. In the capillary network paralleling the myocardial fibers enzyme activity was found positive whereas in the large sinusoidal, endothelial vessels, linking transmurally neighbouring capillaries, there was no alkaline phosphatase activity. In both endothelial cell types, in capillaries and in sinusoids, a transendothelial vesicular thorotrast transport could be shown. It is supposed that the sinusoidal vessels preponderantly have to cope with intercapillary shear stress. Their nutritial function is believed to be of less importance. At least the lack of alkaline phosphatase activity should indicate that there is no selective transendothelial transport in the wall of these sinusoids.

On the significance of fiber branching in the human myocardium.

Myocardial tissue exhibits a high degree of organization in that the cardiac muscle fibers are both systematically aligned and highly branched. In this study, the influence and significance of fiber branching is analyzed mathematically. In order to allow for analytic solutions, a regular geometry and simplified constitutive relations are considered. It is found that branching is necessary to stabilize the ventricular wall.

The anisotropic structure of the human left and right ventricles.

An important determinant of cardiac output derives from the structure of the ventricular wall given by the arrangement of the cardiac muscle fibres. A key feature of this arrangement is both a global and local anisotropy. First, a preparation method necessary for analyzing the main aspects of spatial fibre architecture is outlined. Global anisotropy can be described by a gross band-like structure wrapping both left and right ventricles while local anisotropy results from the arrangement of the individual muscle fibres within the band. In pathologic cases this basic structure may be disturbed leading to cardiac failure. Second, a Finite Element model, formulated on the basis of Magnetic Resonance measurements has been devised which is intended to reflect the global as well as the local anisotropy of the ventricles in order to further the understanding of cardiac performance.

Computation of the alignment of myocardial contractile pathways using a magnetic tablet and an optical method.

The computation of the inclination angle of myocardial contractile pathways, based on the data from (1) optically and (2) manually digitized hearts is described. The measured raw data comprised: (1) A list epi of points on an "epicardial' surface S. (2) For each selected contractile pathway f, a list of points along the contractile pathway. For any point p on a contractile pathway f, the angle of inclination alpha p = alpha p (p,f,S) is defined to be the angle (in degrees) between the tangent tp = tp(f) to the contractile pathway f at the point p and the tangent plane Tvp to the surface S at the surface point up = v(p,S) which is nearest to p. Thus alpha p is a generalization of the imbrication angle of Streeter. The angle of inclination was computed using two separate numerical methods: (1) A discrete method, applying finite differences to the raw data, to compute the tangents tp and the tangent planes Tvp, after which the results were smoothed. (2) A smoothing method in which the data was first smoothed to obtain an approximation Scpi to the epicardial surface and spline approximations to the contractual pathways f. We describe the results for two typical hearts: a manually digitized dilated pig heart and an optically digitized constricted cow heart. For each heart we first present the depths and angles of inclination of typical contractual pathways and then summarize the results in the form of histograms. The results are discussed in detail in the accompanying paper of Lunkenheimer. Redmann et al. [5], where the digitization methods are also described.

The difficult access to morphology of the heart: clinical implications.

The literature on the morphology of the heart is reviewed within the context of recent histological findings. There is strong evidence for a dualistic myocardial function, whereby both ventricular constricting and expanding forces are supposed to act synchronously although with variable effect over the heart cycle.The morphological basis of this dualistic myocardial function is the contorted rope-like structure worn into the bulk of the heart muscle. Opinions are divided about the invasiveness of blunt preparation on the heat denatured heart by which the fascicular architecture is carved out of the muscle. Histology confirms the existence of a fascicular substructure. It results from an inhomogeneous repartition of myocardial fibre branchings and the arrangement of the delicate connective tissue netting by which myocardial strands are bundled and wrapped. One important feature of the fascicular structure of the heart muscle is an oblique transmurally arranged element which yields a force vector opposing systolic wall thickening. This structural element which acts in the direction of ventricular dilation probably gains pathological import in some cases of architectural remodelling, namely in myocardial fibrosis and hypertrophy.

The heart muscle's putative "secondary structure'. Functional implications of a band-like anisotropy.

Opinions are divided as to whether the rope-like secondary structure, which Torrent-Guasp dissected out of the myocardial body by the blunt unwinding technique (BUT) reveals some kind of functional compartmentation of the heart muscle. The myocardial fibres are aligned parallel to the fibre disruption (cleavage) plane, along which the band has been prepared but they are not necessarily aligned parallel to the long axis of the band. Inconsistencies in the myocardial rope model arise from the obligatory zones of transmural inflection, which are obvious in the base and the apex of both ventricles. They are, however, merely discernible in the midzone of the left ventricular cone. The investigator experienced in BUT knows that the cleavage plane is not unique. We doubt the assumption that the rope structure is the predominant stress transmission pathway, because the fibre strand peel-off technique (SPOT) delivers irregular fibre disruption planes which are definitely different from those which Torrent-Guasp prepares. The rope-like fibre arrangement could be just a redundant structure, a remnant of past developmental steps without, however, any functional implication to the human heart. On the other hand, peeling-off fibre strands from the ventricular wall produces deeply perforating, i.e., oblique transmurally grooved surfaces. Putative functions of force transmission in an oblique transmural direction are (1) ventricular dilation as a function of the variable inclination angle with respect to the epicardial surface, (2) monitoring of ventricular wall stress and ventricular size and (3) segmental stiffening which could serve other dependent segments as a punctum fixum.

The heart's fibre alignment assessed by comparing two digitizing systems. Methodological investigation into the inclination angle towards wall thickness.

Myocardial contractile pathways which are not aligned strictly parallel to the heart's epicardial surface, give rise to forces which also act in the ventricular dilating direction. We developed a method which allows us to assess any fibre orientation in the three-dimensional myocardial weave. Decollagenized hearts were prepared by peeling-off fibre strands, following their main fibre orientation down to near the endocardium. In the subepicardium the strands followed a course more or less parallel to the epicardium, whereas from the mid-wall on they tended to dive progressively deeper into the wall. The preparation displays more or less rugged surfaces rather than smooth layers. The grooves and crests on the exposed surfaces were sequentially digitized by two methods: (1) Using a magnet tablet (3 Draw Digitizer System, Polhemus, Cochester VTO 5446, USA) on a dilated pig heart we manually followed the crests using a stylus, handling each groove and crest as an individual contractile pathway. (2) A constricted cow heart was digitized using a contact-free optical system (opto TOP, Dr. Breuckmann, Meersburg, Germany), which is based on the principle of imaging triangulation. Using specially developed software the inclination angles of selected crests and grooves with respect to the epicardial surface were calculated. The two digitizing methods yield comparable results. We found a depth- and side-specific weave component inclined to the epi-endocardial direction. This oblique netting component was more pronounced in the inner 1/3 of the wall than in the subepicardium. The inclination angle probably increases with increasing wall thickness during the ejection period. Manual digitizing is an easy and fast method which delivers consistent results comparable with those obtained by the cumbersome high resolution optical method. The rationales for the assessment of transmural fibre inclination are (1) the putative existence of dilating forces inherent in the myocardial weave and (2) the possible overproportional increase in the oblique transmural weave component during myocardial hypertrophy, which would entail a reduction in efficiency of ventricular performance in terms of haemodynamic work.

The assessment of intramural stress alignment on the beating heart in situ using micro-ergometry: functional implications.

The main local stress transmission pathways in the left ventricular base, midportion and apex in up to seven layers have been assessed in normal dog and porcine hearts, in hypertrophied dog hearts, and in three pig hearts having undergone a temporary left ventricular outflow stricture. The rotational sensitivity of needle force probes was used to determine the focal surface-parallel direction of the myocardial tension vector. In all places investigated the orientation of the force transmission pathways differs slightly from the morphologically determined fibre alignment. Vector rotation upon an axis normal to the epicardial surface is definitely tempered as compared to fibre rotation. Alterations in the force transmission pathways assessed in hypertrophied dog hearts by micro-ergometry qualitatively confirm structural remodelling in so far as an irregularity in the transmural rotation of the main stress vector was found. The measured disparities between the alignment of the myocardial fibre weave and the direction of stress transmission both in the normal and the diseased heart is widely individual, and hence, scattering of the data is marked. However, it must also be called into consideration that the measured orientation of force vectors is that at the moment of highest developed force, only. Further investigations will elucidate if discrepancies between that force vector and morphology are less pronounced when the vector is averaged over the entire heart cycle.

Inhomogeneities in wall stress measured by microergometry in the heart muscle in situ.

Microergometry is a method which we have developed as a tool to measure local mesh-tension within the myocardial weave at any measuring site of both ventricles and the septum on the beating heart in situ. In a mapping procedure on pig and dog hearts, both in control conditions and in the hypertrophied state after aortic banding, local mesh-tension was measured in several areas and in up to eight depths proceeding from the epicardium to the endocardium: Probe-to-fibre coupling is definitely more stable in the canine myocardium than in the porcine heart muscle, probably due to a more effective connective tissue fettering of the canine myocardial weave. The observed longitudinal gradient, with the highest tension in the base, of control dog hearts was levelled out in the hypertrophied hearts. Furthermore, in control dog hearts mesh-tension in the subepi- and subendocardial layers was higher than in the midlayers. This pronounced midlayerhypotension was smoothed in the hypertrophied hearts. Further studies will be dedicated to the question of whether the impact of ventricular size and shape on intersegmental stress transmission is determined by the Frank-Starling mechanism alone or whether protracted remodelling processes on the level of the local fibre weave cause slow coupling alterations.

[High frequency ventilation. Study of the mechanisms of action]. / Ventilation à haute fréquence. Etude des mécanismes d'action.

Dried lungs and isolated bronchial trees dissected from large animals were submitted to high-frequency oscillation and jet-ventilation. The pattern of intrapulmonary pressure distribution and CO2 diffusion were measured through transalveolar chambers fixed to the perforated pleural surfaces and through airbags pasted on the isolated bronchial trees. Under oscillating conditions, the pressure profiles in different lung and bronchial compartments were inhomogeneous and frequency dependent; the pressure-wave amplitude was proportional to the oscillation frequency. On the other hand, the inhomogeneities found with jet-ventilation were mostly dependent on the airflow direction and position of the intratracheal cannula. Since these inhomogeneities were similar on dissected lungs as well as on isolated bronchial trees, it was concluded that they were essentially dependent on endobronchial aerodynamic effects. But the absence of the in vivo pulmonary and bronchial elastic recoil certainly modified the effects of these ventilation modes with respect to accepted clinical findings. Also results were shown to vary between individuals and within individuals, probably explaining the divergent results obtained by different authors.

[Ventilation by high frequency oscillations in adults. An experimental study of conditions and methods]. / La ventilation par oscillations ä haute fréquence chez l'adulte. Etude expérimentale des conditions de réalisation.

A hydraulic pump with an adjustable stroke delivering up to 145 ml at 1 to 45 Hz has been used to ventilate adult pigs of a weight between 60 and 140 kg. After tracheotomy the curarized animals were connected to the pump by a metallic tube through which a bias flow was directed. This flow (FiO2 0.35) was humidified by a special ceramic device and aspirated at the distal end of the tube. It was demonstrated that under these conditions gaz exchange was well maintained with oscillations between 15 and 35 Hz. Higher frequencies were needed for the heavier animals. Blood gas measurements of samples from segmental pulmonary veins demonstrated regional differences in gas exchange. These could be modified by adjusting the oscillation frequency. Reinhalation of gas could be prevented by an increase of the bias flow. Alveolar recruitment by initial pulmonary inflation by a pressure of 18 +/- 2 cm H2O is required for adequate oxygenation. Maintenance of adequate elimination of CO2 required a bias flow of 35 +/- 5 l/min. Mean pressure in the airways was maintained at 12 +/- 1 cm H2O. This pressure determines the value of PaO2. Ordinary endotracheal tubes tend to collapse during the sucking phase of the pressure cycle. Rigid or armed tubes are required. They must allow for aspiration of the bias flow from the distal end of the tube.

A mathematical model of the mechanical link between shortening of the cardiomyocytes and systolic deformation of the left ventricular myocardium.

BACKGROUND: Left ventricular myocytes are arranged in a complex three-dimensional mesh. Since all myocytes contract approximately to the same degree, mechanisms must exist to enable force transfer from each of these onto the framework as a whole, despite the transmural differences in deformation strain. This process has hitherto not been clarified in detail. OBJECTIVE: To present a geometrical model that establishes a mechanical link between the three-dimensional architecture and the function of the left ventricular myocardium. METHODS: The left ventricular equator was modeled as a cylindrical tube of deformable but incompressible material, composed of virtual cardiomyocytes with known diastolic helical and transmural angles. By imposing reference circumferential, longitudinal, and torsional strains onto the model, we created a three-dimensional deformation field to calculate passive shortening of the myocyte surrogates. We tested two diastolic architectures: 1) a simple model with longitudinal myocyte surrogates in the endo- and epicardium, and circular ones in the midwall, and 2) a more accurate architecture, with progressive helical angle distribution varying from -60° in the epicardium to 60° in the endocardium, with or without torsion and transmural cardiomyocyte angulation. RESULTS: The simple model caused great transmural unevenness in cardiomyocyte shortening; longitudinal surrogates shortened by 15% at all depths equal to the imposed longitudinal strain, whereas circular surrogates exhibited a maximum shortening of 23.0%. The accurate model exhibited a smooth transmural distribution of cardiomyocyte shortening, with a mean (range) of 17.0 (13.2-20.8)%. Torsion caused a shortening of 17.0 (15.2-18.9)% and transmural angulation caused a shortening of 15.2 (12.4-18.2)%. Combining the effects of transmural angulation and torsion caused a change of 15.2 (13.2-16.5)%. CONCLUSION: A continuous transmural distribution of the helical angle is obligatory for smooth shortening of the cardiomyocytes, but a combination of torsional and transmural angulation changes is necessary to execute systolic mural thickening whilst keeping shortening of the cardiomyocytes within its physiological range.