Epicardial suction: a new approach to mechanical testing of the passive ventricular wall

The lack of an appropriate three-dimensional constitutive relation for stress in passive ventricular myocardium currently limits the utility of existing mathematical models for experimental and clinical applications. Previous experiments used to estimate parameters in three-dimensional constitutive relations, such as biaxial testing of excised myocardial sheets or passive inflation of the isolated arrested heart, have not included significant transverse shear deformation or in-plane compression. Therefore, a new approach has been developed in which suction is applied locally to the ventricular epicardium to introduce a complex deformation in the region of interest, with transmural variations in the magnitude and sign of nearly all six strain components. The resulting deformation is measured throughout the region of interest using magnetic resonance tagging. A nonlinear, three-dimensional, finite element model is used to predict these measurements at several suction pressures. Parameters defining the material properties of this model are optimized by comparing the measured and predicted myocardial deformations. We used this technique to estimate material parameters of the intact passive canine left ventricular free wall using an exponential, transversely isotropic constitutive relation. We tested two possible models of the heart wall: first, that it was homogeneous myocardium, and second, that the myocardium was covered with a thin epicardium with different material properties. For both models, in agreement with previous studies, we found that myocardium was nonlinear and anisotropic with greater stiffness in the fiber direction. We obtained closer agreement to previously published strain data from passive filling when the ventricular wall was modeled as having a separate, isotropic epicardium. These results suggest that epicardium may play a significant role in passive ventricular mechanics.     

X-ray diffraction from a left ventricular wall of rat heart

We studied x-ray diffraction from the left ventricular wall of an excised, perfused whole heart of a rat using x rays from the third-generation synchrotron radiation facility, SPring-8. With the beam at right angles to the long axis of the left ventricle, well-oriented, strong equatorial reflections were observed from the epicardium surface. The reflections became vertically split arcs when the beam passed through myocardium deeper in the wall, and rings were observed when the beam passed into the inner myocardium of the wall. These diffraction patterns were explained by employing a layered-spiral model of the arrangement of muscle fibers in the heart. In a quiescent heart with an expanded left ventricle, the muscle fibers at the epicardium surface were found to have a (1,0) lattice spacing smaller than in the rest of the wall. The intensity ratio of the (1,0) and (1,1) equatorial reflections decreased on contraction with a similar time course in all parts of the wall. The results show that it is possible to assign the origin of reflections in a diffraction diagram from a whole heart. This study offers a basis for interpretation of x-ray diffraction from a beating heart under physiologically and pathologically different conditions.     

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.     

Idiopathic epicardial ventricular arrhythmias: diagnosis and ablation technique from the aortic sinus of Valsalva

Idiopathic outflow tract arrhythmias (ventricular tachycardias or symptomatic premature ventricular contractions; OT-VT/PVCs) can originate from the left ventricular (LV) epicardium (Epi-VT/PVCs), and radiofrequency (RF) energy applications from the aortic sinus of Valsalva can eliminate Epi-VT/PVCs in selected patients. Among the various ECG findings, the R-wave duration index and R/S amplitude index in leads V1 or V2 are useful for identifying Epi-VT/PVCs, and the Q-wave ratio of leads aVL to aVR and S-wave amplitude in lead V1 are useful for differentiating between an Epi-VT/PVC originating from the LV epicardium remote from the left sinus of Valsalva (LSV) and that from the LSV. Tissue tracking imaging is a promising modality for identifying the origin of OT-VT/PVCs and for differentiating between an Epi-VT/PVC originating from the LV epicardium remote from the LSV and that from the LSV. If the origin of the Epi-VT/PVC is identified within the LSV, coronary and aortic angiography should be performed to assess the anatomic relationships between the Epi-VT/PVC origin and coronary arteries and aortic valve before the RF energy delivery. To avoid potential complications, RF ablation should be performed at the LSV using a maximum power of 35 watts and maximum temperature of 55 degrees C. Epicardial mapping through the coronary venous system and the presence of potentials recorded from the ablation site within the LSV and their changes before and after the RF energy applications may be useful for diagnosing Epi-VT/PVCs or predicting a successful catheter ablation from the LSV.     

Tissue tracking imaging for identifying the origin of idiopathic ventricular arrhythmias: a new role of cardiac ultrasound in electrophysiology

Several strategies for mapping ventricular outflow tract tachycardia have been reported as useful indices for differentiating between those originating from the right and the left side. Recently, tissue tracking imaging (TTI) has been demonstrated as a novel non-invasive modality for identifying the origin of outflow tract tachycardias. Tissue tracking imaging is an ultrasonographic technique that measures the myocardial motion amplitude towards the transducer in each region during systole, identifying regional myocardial displacement on the basis of myocardial velocities using color Doppler myocardial imaging principles. In this technique, the origin of the arrhythmia could be recognized as the site where the earliest color-coded signal (ECCS) appeared on the myocardium at the onset of the systole. In preliminary studies this modality was found to be useful in differentiating outflow tract ventricular tachycardias. ECCS was always found below or at the level of the pulmonary valve in all arrhythmias which could be ablated from the right ventricular outflow tract, while in those where the ECCS was above and close to the pulmonary valve it could be ablated from the left sinus of valsalva. These results indicate that TTI can provide detailed and accurate information on the arrhythmia origin of outflow tract tachycardia and may be useful for differentiating between an outflow tract tachycardia originating from the LV epicardium remote from the LSV and that from the LSV. Newer advances in echocardiographic technologies like high resolution, high frame rate real time three dimensional echocardiography with speckle tracking may further improve the precise localization of arrhythmias in the future.     

Repolarization of canine ventricular myocardium under the supraventricular rhythm

The ventricular myocardium is characterized by heterogeneity of activation-recovery interval durations. The transmural ARI gradients are present in the right ventricular apex (ARIs monotonically decreased as one moved from the endocardium to the epicardium), and in the left ventricular base (repolarization in the subepicardial layers was significantly shorter than that in the midmyo cardial layers whereas subendocardial ARIs did not differ from the others). The repolarization pattern of these myocardial regions is governed by the distribution of ARIs. In the apical left ventricular and basal right ventricular areas, no significant transmural differences in the repolarization durations were found. The repolarization pattern of these myocardial regions is governed by the activation sequence. In the right ventricle, ARIs were significantly longer at the base and shorter at the apex. In contrast, in the left ventricle, the apical ARIs were prolonged whereas the basal ARIs were abbreviated. The apex-to-base sequence of myocardial repolarization seems to depend on apex-to-base gradient of activation-recovery intervals durations.     

Right ventricular TNF resistance during endotoxemia: the differential effects on ventricular function

Right and left ventricular myocytes originate from different cellular progenitors; however, it is unknown whether these cells differ in their response to endotoxemia. We hypothesized that 1) the percentage of endotoxemic functional depression within the right ventricle (RV) would be smaller than that of the left ventricle; and 2) that better RV function would correlate with lower levels of right ventricular TNF production. Adult Sprague-Dawley rats were divided into right and left control and endotoxin groups. Controls received vehicle, while endotoxin groups received LPS at 20 mg/kg ip. Hearts were excised either 2 or 6 h after injection. Hearts excised at 2 h were assayed for TNF, IL-6, TNF receptor 1 (TNFR1), TNFR2, and via ELISA, while hearts excised at 6 h were assayed via the Langendorff model. The percentage of cardiac functional depression, exhibited as developed pressure, contractility, and rate of relaxation (expressed as a percentage of control) was significantly smaller in right ventricles compared with left ventricles following endotoxin exposure. Tissue levels of TNF were significantly elevated in both right and left ventricles 2 h after endotoxin exposure, and right ventricular endotoxin groups expressed higher levels of TNF compared with their left ventricular counterparts. No significant differences in IL-6, TNFR1, or TNFR2 levels were noted between endotoxin-exposed ventricles. This is the first study to demonstrate that right and left ventricular function differs after endotoxin exposure.     

Transitions in human atrial and ventricular myosin light-chain isoenzymes in response to cardiac-pressure-overload-induced hypertrophy.

1. The light-chain subunits of human atrial and ventricular cardiac muscle were examined by two-dimensional polyacrylamide-gel electrophoresis and limited proteolytic digestion. The light-chain patterns in the normal right and left atria were identical. 2. Myosin preparations isolated from right or left atria that had been subjected to cardiac-pressure-overload-induced hypertrophy also contained ventricular light-chain subunits. These were identified by peptide mapping in sodium dodecyl sulphate. 3. Ventricular light chain-2 was the major species in hypertrophied atria, although light chain-1 subsequently appeared in severe pressure-overload-hypertrophied cases. Evidence is presented for the existence of more than one form of ventricular light chain-2. 4. The transition from atrial to ventricular myosin light chains correlated with the degree of pressure-overload hypertrophy in 83 examples of surgically excised atria. 5. The adult atrial light chain-1 was shown to be homologous to the human foetal ventricular light chain-1 [Price, Littler & Cummins (1980) Biochem. J. 191, 571-580] by peptide mapping. 6. A scheme of atrial/ventricular myosin light-chain isoenzyme transitions is discussed in relation to changing contractile properties in cardiac muscle, together with implications for the role of light-chain subunits.     

Cardioelectric field on the atrial surface in pigs

The form and distribution of extracellular cardioelectric potentials and the sequence of the excitation wave propagation on epicardium of the pig atria were studied by the method of multichannel synchronous cardioelectrotopography. The studies have shown that in pig the excitation wave breaks on epicardium of the right atrium at the base of the upper vena cava. Negative initial atrial complexes are registered in this area. Two fronts of excitation wave spread from the zone of initial epicardial activation: one--to upper segments of dorsal and ventral sides of the right atrium, the second--to inter-atrial septum. The excitation wave comes to the left atrium with a delay relative to the beginning of depolarization of the right atrium. On account of the successive movement of the front of the excitation wave from pacemaker the two-phase potentials are formed on greater part of the epicardium of the pig atria. The lower part of the auricle of the left atrium is depolarized in atrial epicardium in the last turn. The sequence of excitation wave propagation in atrial epicardium close to ravenous (dog) and ungulate (sheep) animals and man is typical for the pig, but herewith the differences in time of covering the atria with excitation do exist.     

Evolution and Development of Ventricular Septation in the Amniote Heart

During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations.     

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.     

Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial compaction

Background

Morphological and functional differences of the right and left ventricle are apparent in the adult human heart. A differential contribution of cardiac fibroblasts and smooth muscle cells (populations of epicardium-derived cells) to each ventricle may account for part of the morphological-functional disparity. Here we studied the relation between epicardial derivatives and the development of compact ventricular myocardium.

Results

Wildtype and Wt1^CreERT2/+ reporter mice were used to study WT-1 expressing cells, and Tcf21^lacZ/+ reporter mice and PDGFRα^-/-;Tcf21^LacZ/+ mice to study the formation of the cardiac fibroblast population. After covering the heart, intramyocardial WT-1+ cells were first observed at the inner curvature, the right ventricular postero-lateral wall and left ventricular apical wall. Later, WT-1+ cells were present in the walls of both ventricles, but significantly more pronounced in the left ventricle. Tcf21-^LacZ + cells followed the same distribution pattern as WT-1+ cells but at later stages, indicating a timing difference between these cell populations. Within the right ventricle, WT-1+ and Tcf21-lacZ+ cell distribution was more pronounced in the posterior inlet part. A gradual increase in myocardial wall thickness was observed early in the left ventricle and at later stages in the right ventricle. PDGFRα^-/-;Tcf21^LacZ/+ mice showed deficient epicardium, diminished number of Tcf21-^LacZ + cells and reduced ventricular compaction.

Conclusions

During normal heart development, spatio-temporal differences in contribution of WT-1 and Tcf21-^LacZ + cells to right versus left ventricular myocardium occur parallel to myocardial thickening. These findings may relate to lateralized differences in ventricular (patho)morphology in humans.     

A Three-Dimensional Analytical (Rheological) Model of the Human Left Ventricle in Passive-Active States: Nontraumatic Determination of the In Vivo Values of the Rheological Parameters

In this paper a three-dimensional continuum model of a mammalian left ventricle is formulated. The stresses in the model satisfy the conditions of zero stress on the outer (epicardial surface-representing) boundary. The strains of the model are obtained from the actual dynamic geometry measurements (obtained from cineangiocardiography). Since the left ventricular muscle is incompressible, the dilatational strain is zero and hence the (three-dimensional) deviatric stress components are related to the corresponding strain components by Maxwell and Voigt rheological model analogues of one-dimensional systems; the parameters of the model are series and parallel elastic (SE, PE) elements and the contractile element (CE) (representing the sarcomere). The incorporation of the rheological features of the cardiac muscle into the three-dimensional constitutive equations (for the three-dimensional continuum model of the left ventricle) is a feature of this paper. A procedure is presented to determine the parameters of the constitutive equations (i.e., the SE, PE, and the parameters of the force-velocity relation for the CE) for the left ventricle of a subject from data on the dimensions and chamber pressure of the left ventricle. The values of these parameters characterize the rheology of the left ventricular muscle of the subject. In order to demonstrate clinical application of the analyses, in vivo data of the subjects' left ventricular pressure and dimensions are obtained, and the analyses are applied to the data to determine (for each subject) the values and characteristics of the elastic elements and CEs.     

Left ventricular myocardal activation under ventricular paced beats in chickens Gallus gallus domesticus

The aim of the study was to advance our knowledge regarding the activation process of the ventricular myocardium in birds in which Purkinje fibres penetrate into the ventricular wall to reach the epicardium. A depolarization pattern of the left ventricular free wall was studied in chickens (Gallus gallus) during ventricular paced beats. Duration of the activation process of the left ventricular free wall is significantly increased during ventricular ectopic excitation as compared with sinus rhythm. Its lowest increase occurs during subendocardial pacing of the middle part of the left ventricle, but its greatest increase is observed during subepicardial pacing of the left ventricular base. Multifocality and mosaicity of depolarization of the left ventricular free wall myocardium in chicken are expressed in a considerably less degree during ventricular paced beats in comparison with sinus rhythm. During ventricular paced beats, excitation of the left ventricular free wall is mostly due to the successive spreading of the depolarization wave from pacing sites.     

Evaluation of hypertrophic cardiomyopathy: new horizons for CMR?

Cardiac magnetic resonance imaging (CMR) is an accurate and reliable means of evaluating cardiac morphology, ventricular function, and myocardial perfusion, both for the left and the right ventricle thereby covering a whole spectrum of cardiac diseases. 1 CMR is therefore very well suited for identifying and characterising patients with various manifestations of left ventricular hypertrophy (LVH).     

Normalisation of the ECG in a patient with right bundle branch block by cardiac pacing

Right ventricular apical pacing (RVA) appears to have potential deleterious effects on myocardial systolic and diastolic left ventricular function, especially in patients with intact AV conduction. Therefore, new pacing sites in the right ventricle are being explored to overcome these detrimental effects. Alternative pacing sites in the right ventricle are the right ventricular outflow tract (RVOT) and the right ventricular septum (RVS). In this case report, we demonstrate an exceptional form of ventricular fusion, namely normalisation of the QRS complex in a patient with pre-existing right bundle branch block by RVS pacing. To our knowledge, this is the first report in the literature where right ventricular pacing could restore a complete RBBB to a normal QRS complex by stimulating distally from the anatomical position of the RBBB, due to fusion between artificial right ventricular stimulation and intrinsic conduction over the left bundle of the specific His-Purkinje system.     

Determination of a constitutive relation for passive myocardium: II. Parameter estimation

In the first paper of this series, we proposed a new transversely isotropic pseudostrain-energy function W for describing the biomechanical behavior of excised noncontracting myocardium. The specific functional form of W was inferred directly from biaxial data to be a polynomial function of two coordinate invariant measures of the finite deformation and five material parameters. In this paper, best-fit values of the material parameters are determined from biaxial data using a nonlinear least-squares regression. These values of the parameters are shown to be well-determined, and the final constitutive relation is shown to have good predictive capabilities. Since the proposed constitutive relation describes much broader classes of in-vitro biaxial data than previously proposed relations, it may be better applicable to analyses of stress in the passive heart.     

Depolarisation and repolarisation sequences of ventricular epicardium in chickens (Gallus gallus domesticus)

Activation and recovery sequences were mapped by means of 64-channel synchronous recording of extracellular potentials on ventricular epicardium in chickens. Ventricular epicardium was depolarized due to multiple breakthroughs. The recovery of ventricular epicardium occurs from the apex to the base of heart and does not repeat the activation sequence. Gradients of repolarisation exist over the ventricular epicardium in birds. Repolarisation pattern of ventricular epicardium depends primarily on intrinsic spatial heterogeneities of ARIs over epicardium.     

A theoretically-based experimental approach for identifying vascular constitutive relations

We employ a structurally-motivated phenomenological formulation to identify biomechanical experiments which can be used to determine a vascular constitutive relation directly from data. Large deformations, nonlinear material behavior, load-dependent anisotropy, material heterogeneity and incompressibility are accounted for in the analysis. For purposes of illustration, we outline a procedure for studying elastic arteries wherein the behavior of the media and adventitia is considered separately. This general approach for identifying vascular constitutive relations can be applied to any vessel or airway, however, and should provide certain advantages over previous microstructural or purely phenomenological formulations.     

Effect of an increase in coronary perfusion on transmural ventricular repolarization

The effect of increased coronary flow on transmural ventricular repolarization was investigated in six pentobabital-anesthetized sheep. Fresh blood at 10 ml/min was injected into the left circumflex coronary artery (LCX) in addition to the normal coronary flow. Unipolar electrocardiograms were simultaneously registered from epicardium, mid-myocardium and endocardium with fine plunge needles. Activation-recovery interval (ARI) was measured from the unipolar electrocardiograms and was used for estimating the ventricular repolarization duration. It was found that intracoronary blood injection (n=3) prolonged ARI in the epicardium, mid-myocardium and endocardium by an average of 34 +/- 16, 28 +/- 18 and 25 +/- 13 ms, respectively (p<0.01). Pretreatment with nitro-L-arginine (n=3), a nitric synthase inhibitor, diminished the flow-induced ARI prolongation across the ventricular wall. In conclusion, an increase in coronary flow lengthens the duration of transmural ventricular repolarization. These effects appear to be mediated by nitric oxide from the coronary endothelium.