Comprehensive MRI for the detection of subtle alterations in diastolic cardiac function in apoE/LDLR–/– mice with advanced atherosclerosis

ApoE/LDLR^–/– mice represent a reliable model of atherosclerosis. However, it is not clear whether cardiac performance is impaired in this murine model of atherosclerosis. Here, we used MRI to characterize cardiac performance in vivo in apoE/LDLR^–/– mice with advanced atherosclerosis. Six‐month‐old apoE/LDLR^–/– mice and age‐matched C57BL/6J mice (control) were examined using highly time‐resolved cine‐MRI [whole‐chamber left ventricle (LV) imaging] and MR tagging (three slices: basal, mid‐cavity and apical). Global and regional measures of cardiac function included LV volumes, kinetics, time‐dependent parameters, strains and rotations. Histological analysis was performed using OMSB (orceine with Martius, Scarlet and Blue) and ORO (oil red‐O) staining to demonstrate the presence of advanced coronary atherosclerosis. MR‐tagging‐based strain analysis in apoE/LDLR^–/– mice revealed an increased frequency of radial and circumferential systolic stretch (25% and 50% of segments, respectively, p ≤ 0.012), increased radial post‐systolic strain index (45% of segments, p = 0.009) and decreased LV untwisting rate (?30.3° (11.6°)/cycle, p = 0.004) when compared with control mice. Maximal strains and LV twist were unchanged. Most of the cine‐MRI‐based LV functional and anatomical parameters also remained unchanged in apoE/LDLR^–/–mice, with only a lower filling rate, longer filling time, shorter isovolumetric contraction time and slower heart rate observed in comparison with control mice. The coronary arteries displayed severe atherosclerosis, as evidenced by histological analysis. Using comprehensive MRI methods, we have demonstrated that, despite severe coronary atherosclerosis in six‐month‐old apoE/LDLR^–/– mice, cardiac performance including global parameters, twist and strains, was well preserved. Only subtle diastolic alterations, possibly of ischemic background, were uncovered. Copyright © 2016 John Wiley & Sons, Ltd.     

Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction

Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.     

A curvature-based approach for left ventricular shape analysis from cardiac magnetic resonance imaging

It is believed that left ventricular (LV) regional shape is indicative of LV regional function, and cardiac pathologies are often associated with regional alterations in ventricular shape. In this article, we present a set of procedures for evaluating regional LV surface shape from anatomically accurate models reconstructed from cardiac magnetic resonance (MR) images. LV surface curvatures are computed using local surface fitting method, which enables us to assess regional LV shape and its variation. Comparisons are made between normal and diseased hearts. It is illustrated that LV surface curvatures at different regions of the normal heart are higher than those of the diseased heart. Also, the normal heart experiences a larger change in regional curvedness during contraction than the diseased heart. It is believed that with a wide range of dataset being evaluated, this approach will provide a new and efficient way of quantifying LV regional function.     

Dynamic stiffness and implications for assisting the operation of the left ventricle

The distribution of bending strain and stiffness in the wallof the left ventricle (LV) is relevant to the augmentation ofits function by a modified skeletal-muscle wrap in the new surgicalprocedure of cardiomyoplasty. A novel approach to ventricularmechanics is presented which blends some finite-element resultsin engineering with new data available on ventricular geometry.Two simplified axisymmetric strip-element models of the LV areused to illustrate aspects of myocardial stiffness in the bending-strain-energydistribution and the effect on wrap synchronization of a changein cross-fibre stiffness when the heart has nonuniform or ectopicbeats. The nonlinear and time-dependent nature of both dampingand wall stiffness is derived from differential equations governingthe dynamic paths from systole to diastole of finite wall elementsaround the periphery of an oblique LV slice using magnetic resonanceimaging (MRI) data. This leads to a geometric method for determiningthese parameters. Results for time-dependent stiffnesses ofelements in their trajectories are presented for a normal heart.     

Regional myocardial function at the papillary muscle insertion site

The importance of the mitral apparatus to the global left ventricular (LV) function has been suggested in several clinical studies. One recent study reported that chordal transsection induced an unloading of myocardium at the papillary muscle insertion site. We hypothesized that the regional response for afterloading at this site with intact mitral apparatus was different from that at the free wall. We investigated the end-systolic pressure-regional segment length relations (ESPLR) in two anterior LV sites, free wall (FREE) and the papillary muscle insertion site (PAP), during an increasing afterload by aortic occlusion in 7 anesthetized open-chest dogs. To measure the regional segment length at FREE and PAP, two sets of the pair of sonomicrometer crystals were implanted in the same midwall depth at the same circumferential hoop by using an echocardiographic guide. ESPLR both at FREE and PAP were always highly linear in a physiological range (r > or = 0.9). The slope of this relation at FREE (274 +/- 164 mmHg/mm) was significantly steeper than that at PAP (157 +/- 118 mmHg/mm) for each dog (p < 0.05). These data indicate that the regional response for afterloading at PAP loaded by chordal tension is different from that at FREE in the same heart.     

Decreased left ventricular torsion and untwisting in children with dilated cardiomyopathy

The purpose of this study was to analyze left ventricular (LV) torsion and untwisting, and to evaluate the correlation between torsion and other components of LV contraction in children with dilated cardiomyopathy (DCM). Segmental and global rotation, rotational rate (Vrot) were measured at three levels of LV using the two dimensional (2D) speckle tracking imaging (STI) method in 10 DCM patients (range 0.6-15 yr, median 6.5 yr, 3 females) and 17 age- and sex-matched normal controls. Global torsion was decreased in DCM (peak global torsion; 10.9 +/- 4.6 degrees vs. 0.3 +/- 2.1 degrees , p<0.001). Loss of LV torsion occurred mainly by the diminution of counterclockwise apical rotation and was augmented by somewhat less reduction in clockwise basal rotation. In DCM, the normal counterclockwise apical rotation was not observed, and the apical rotation about the central axis was clockwise or slightly counterclockwise (peak apical rotation; 5.9 +/- 4.1 degrees vs. -0.9 +/- 3.1 degrees , p<0.001). Systolic counterclockwise Vrot and early diastolic clockwise Vrot at the apical level were decreased or abolished. In DCM, decreased systolic torsion and loss of early diastolic recoil contribute to LV systolic and diastolic dysfunction. The STI method may facilitate the serial evaluation of the LV torsional behavior in clinical settings and give new biomechanical concepts for better management of patients with DCM.     

Force interval relationship (FIR) related to the global function of the left ventricle: a computer study

A model which relates the left ventricular (LV) geometry, structure and sarcomere properties to its global function, recently proposed by the authors, is extended to account for contractility changes which are a function of the heart rate, prematurity of the beat and calcium transients within the cell. To characterise LV function and relate it to fibre function under varying rhythm conditions, a model of muscle force restitution, based on calcium kinetics, was used to calculate the maximum fibre stress at the optimum sarcomere length sigma o as the parameter which depends on the heart rate, the test pulse interval TPI, the action potential duration APD and the restitution time constant. The global LV force interval relationship FIR was then calculated, and by comparing the calculated FIR to the experimental measurement (in dogs) at the ventricular level, the constants of the restitution of force at the fibre level were derived. Based on these constants, the LV function under ejecting conditions at various rhythm disturbances was calculated and related to the local, distributed parameters. This approach provides a tool to describe ventricular function as well as transmural distribution of stress and sarcomere length at a wide variety of loading and rhythm conditions based on given 'muscle level' parameters.     

Cardiocirculatory bio-assist: is it time to reconsider demand dynamic cardiomyoplasty? Review and future perspectives

In the last 15 years, dynamic cardiomyoplasty has remained an experimental procedure even after the enthusiastic short- and mid-term results, mainly because of the disappointing long-term outcome caused by muscular degeneration secondary to chronic continuous electrical stimulation of the latissimus dorsi. In Italy, a group of muscular pathologists, cardiologists, and cardiac surgeons conducted an experiment of an activity-rest stimulation protocol in humans that should avoid complete transformation of the skeletal muscle, maintaining its properties overtime. This "demand" stimulation protocol gave good results, improving New York Heart Association class, ejection fraction value, and survival. Even though dynamic cardiomyoplasty was excluded from the recent international guidelines for the management of heart failure, the discussion on the ability of this unique kind of cardiocirculatory bio-assistance is due to be reopened, thanks to the results of the new stimulation protocol. Heart transplantation, circulatory supporting devices, multisite stimulation therapy, and the total artificial heart are not always and in all countries the best solutions: the great economic cost, the numerous contraindications, the need for immunosuppression and antithrombotic therapy, and the troublesome follow up constitute important drawbacks. For patients in whom transplant surgery cannot be performed, as well as in developing countries, the nonprohibitively expensive demand dynamic cardiomyoplasty may still play a role.     

An Engineering Model of Dynamic Cardiomyoplasty. I.

Dynamic cardiomyoplasty (DCM) is an emerging surgical procedure for heart failure in which the patient's latissimus dorsi (LD) muscle is wrapped around the heart and stimulated to contract in synchrony with the heartbeat as a cardiac assist measure. A 6 week training protocol of progressive electrical stimulation renders the normally fatigueable skeletal muscle fatigue-resistant and suitable for chronic stimulation. To date, over 500 procedures have been performed in worldwide clinical trials. Investigators typically report symptomatic improvement and modest hemodynamic improvement in patients. Controversy exists regarding the exact mechanism of DCM. To test the hypothesis that DCM augments cardiac stroke volume through improvement in systolic function, we formulated an engineering model of dynamic cardiomyoplasty to predict stroke volume. The heart and the LD were modeled as nested (series) elastance chambers, and the vasculature was represented by a two-element Windkessel model. Using five healthy goats, we verified model predictions of stroke volume for both stimulator ON beats (y=1.00x–0.08, r=0.87, p < 0.0001) and OFF beats (y=1.01x+1.06, r=0.91, p < 0.0001), where x and y are the measured and predicted stroke volumes, respectively. The model confirms that using untrained latissimus dorsi applied to the normal myocardium produces only moderate increases in stroke volume and suggests that future research should focus on increasing LD strength after training.     

Histopathological findings in skeletal muscle used in human dynamic cardiomyoplasty

Patients submitted to dynamic cardiomyoplasty had an initial clinical improvement followed by a decrease in cardiac failure indices. A histopathological study of the skeletal muscle was undertaken to explain this. Latissimus dorsi fragments from 15 patients submitted to dynamic cardiomyoplasty in a 1:1 (heart beat:muscle stimulation) conditioning were analysed by light microscopy. The interval between surgery and obtaining the specimens (13 from necropsies, two from heart transplants) ranged from 37 days to 6 years. Nuclear clumps and internalization, the presence of round fibres, inflammation, and fibrosis were analysed semi-quantitatively; the thickness of muscle fibres and the percentage of tissue fat were measured by image analysis. The quantitative data were also compared, in 12 cases, with gender- and age-matched necropsy controls. The mean thickness of muscle fibres in cases and controls was 27.21+/-5.33 and 40.84+/-9.42 microm, respectively (p=0.001). The percentage of tissue fat in cases and controls was 12.04+/-12.66% and 0.93+/-0.91%, respectively (p=0.008). The duration of grafts correlated positively with the quantity of nuclear clumps (R=0.80, p<0.001) and round fibres (R=0.53, p=0.04), as well as with the percentage of tissue fat (R=0.68, p=0.005). Accordingly, a negative correlation was found between the duration of grafts and the mean diameter of fibres, characterizing muscle atrophy (R=-0.66, p=0.01). The longer the post-surgical period, the more intense the degenerative lesions. This study shows that skeletal muscle used in human dynamic cardiomyoplasty may atrophy and be replaced by fat when stimulation is synchronized to every cardiac beat. These findings could play a role in explaining the long-term results of this surgical procedure.     

Detection of skeletal muscle fatigue using an accelerometer in dynamic cardiomyoplasty

 An animal experiment was done using six mongrel dogs that weighed 28 ± 3 kg to show that an accelerometer could detect skeletal muscle fatigue in dynamic cardiomyoplasty. Through left-side thoracotomy, the heart was exposed and an electrode to sense the heartbeat was positioned on the left ventricle. A left latissimus dorsi muscle flap (LDMF) was inserted into the left chest cavity and rolled around the heart. An accelerometer was put on the rolled LDMF to sense the ventricular acceleration by contraction of the LDMF and the heart. The LDMF was stimulated under these settings: pulse width, 210 μs; stimulation output, 6 V; burst frequency, 30 Hz; burst duration, 200 ms; synchronous ratio, 1 : 4; and synchronous delay, 66 ms. Output voltage from the accelerometer was recorded 1, 3, 5, 10, and 15 min after the beginning of stimulation. Percentages of the amplitude in all dogs after 3, 5, 10, and 15 min were 81 ± 10%, 63 ± 12%, 48 ± 11%, and 45 ± 14% of the values after 1 min, respectively. Significant differences were found between the values after 1 min and those after 3 min, between the values after 3 min and those after 5 min, and between the values after 5 min and those after 10 min. This study suggests that muscle fatigue is detectable with an accelerometer in actual dynamic cardiomyoplasty. Received: May 11, 2001 / Accepted: September 10, 2002 Acknowledgments This work was financially supported in a part by a Grant in Aid for Scientific Research (05671113) from the Ministry of Education, Science, and Culture of Japan. Correspondence to:H. Kuroda     

A novel, view-independent method for strain mapping in myocardial elastography: eliminating angle and centroid dependence

Robust indices of regional and global cardiac function are a key factor in detection and treatment of heart disease as well as understanding of the fundamental mechanisms of a healthy heart. Myocardial elastography provides a noninvasive method for imaging and measuring displacement and strain of the myocardium for the early detection of cardiovascular disease. However, two-dimensional in-plane axial and lateral strains measured depend on the sonographic view used. This becomes especially critical in a clinical setting and may induce large variations in the measured strains, potentially leading to false diagnoses. A novel method in myocardial elastography is proposed for eliminating this view dependence by deriving the polar, principal and classified principal strains. The performance of the proposed methodology is assessed by employing 3D finite-element left-ventricular models of a control and an ischemic canine heart. Although polar strains are angle-independent, they are sensitive to the selected reference coordinate system, which requires the definition of a centroid of the left ventricle (LV). In contrast, principal strains derived through eigenvalue decomposition exhibit the inherent characteristic of coordinate system independence, offering view (i.e., angle and centroid)-independent strain measurements. Classified principal strains are obtained by assigning the principal components in the physical ventricular coordinate system. An extensive strain analysis illustrates the improvement in interpretation and visualization of the full-field myocardial deformation by using the classified principal strains, clearly depicting the ischemic and non-ischemic regions. Strain maps, independent of sonographic views and imaging planes, that can be used to accurately detect regional contractile dysfunction are demonstrated.     

Automatic Classification of Left Ventricular Regional Wall Motion Abnormalities in Echocardiography Images Using Nonrigid Image Registration

Identification and classification of left ventricular (LV) regional wall motion (RWM) abnormalities on echocardiograms has fundamental clinical importance for various cardiovascular disease assessments especially in ischemia. In clinical practice, this evaluation is still performed visually which is highly dependent on training and experience of the echocardiographers and therefore suffers from significant interobserver and intraobserver variability. This paper presents a new automatic technique, based on nonrigid image registration for classifying the RWM of LV in a three-point scale. In this algorithm, we register all images of one cycle of heart to a reference image (end-diastolic image) using a hierarchical parametric model. This model is based on an affine transformation for modeling the global LV motion and a B-spline free-form deformation transformation for modeling the local LV deformation. We consider image registration as a multiresolution optimization problem. Finally, a new regional quantitative index based on resultant parameters of the hierarchical transformation model is proposed for classifying RWM in a three-point scale. The results obtained by our method are quantitatively evaluated to those obtained by two experienced echocardiographers visually as gold standard on ten healthy volunteers and 14 patients (two apical views) and resulted in an absolute agreement of 83 % and a relative agreement of 99 %. Therefore, this diagnostic system can be used as a useful tool as well as reference visual assessment to classify RWM abnormalities in clinical evaluation.     

Quantification of regional myocardial mean intracellular water lifetime: A nonhuman primate study in myocardial stress

Heart failure with preserved ejection fraction (HFpEF) is typically associated with early metabolic remodeling. Noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. Mean intracellular water lifetime (τ_i) has been shown to be partially inversely related to Na, K‐ATPase transporter activity and may thus provide insight into the metabolic status in HFpEF patients. Here, we aim to perform regional quantification of τ_i using dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) in the nonhuman primate (NHP) heart and evaluate its region‐specific variations under conditions of myocardial stress in the context of perturbed myocardial function. Cardiac stress was induced in seven naïve cynomolgus macaques using a dobutamine stepwise infusion protocol. All animals underwent 3 T cardiac dual‐bolus DCE and tagging MRI experiments. The shutter‐speed model was employed to quantify regional τ_i from the DCE‐MR images. Additionally, τ_i values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τ_i (192.9 ± 76.3 ms vs 321.6 ± 70 ms at rest, P < 0.05) in the left ventricle, together with an increase in global peak circumferential strain (?15.4% ± 2.7% vs ?10.1% ± 2.9% at rest, P < 0.05). Specifically, slice‐level analysis further revealed that a greater significant decrease in mean τ_i was observed in the apical region (Δτ_I = 182.4 ms) compared with the basal (Δτ_i = 113.2 ms) and midventricular regions (Δτ_i = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τ_i in the anterior (Δτ_i = 243.9 ms) and antero‐lateral (Δτ_i = 177.2 ms) regions. In the inferior and infero‐septal regions, although a decrease in τ_i was observed, it was not significant. Whole heart regional quantification of τ_i is feasible using DCE‐MRI. τ_i is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.     

Selective Stimulation of Latissimus Dorsi Muscle for Cardiac Assist

The contractile power of the latissimus dorsi muscle (LDM) is used in skeletal muscle cardiac assist (SMCA) to augment the blood pumping ability of a failing heart. The LDM has three anatomically distinct, independently innervate segments—the transverse, oblique, and lateral. There are potential advantages to selectively stimulating these LDM regions. We hypothesized that (1) the three nerve branches could be stimulated selectively to activate individual muscle regions with little or no functional overlap, (2) the three muscle regions would generate similar force, and (3) nerves stimulated in combinations would generate forces corresponding to the sum of forces generated by the individual regions. In acute studies of canine LDM (n=5), regional electromyogram (EMG) and isometric force were recorded while branches of the thoracodorsal nerve were stimulated (via nerve-cuff electrodes) individually and in combinations. Analysis of regional EMG and force confirmed selective activation. Stimulation of lateral, oblique, and transverse branches of thoracodorsal nerve activated 53 ±5%, 20 ± 9%, and 36 ± 9% of the muscle, respectively; with corresponding developed forces of 48 ± 6%, 21 ± 8%, and 31 ± 8% of total muscle force (R=0.98, p < 0.05). Selective activation of LDM is possible with little or no functional overlap; however, the muscle regions were nonuniform. Selective stimulation may ultimately facilitate the use of performance enhancing stimulus protocols for SMCA. © 1999 Biomedical Engineering Society. PAC99: 8717Nn, 8719Ff     

Dynamic cardiomyoplasty in a patient with end-stage cardiomyopathy.

Dynamic cardiomyoplasty is a relatively new surgical procedure by which a transformed fatigue-resistant skeletal muscle wrapped around the heart is stimulated to contract in synchrony with it, thereby augmenting the ventricular functions of a failing heart. We performed a cardiomyoplasty with latissimus dorsii (LD) in a patient who was refused the heart transplant programme because of pulmonary hypertension and psychosocial contraindications. The patient was 34 years old, functional class grade IV of the New York Heart Association (NYHA), with a three-month history, due to ischemic cardiomyopathy with multiple vessels affected, 10% ejection fraction, arteriolar pulmonary resistance of 7.5 U Wood. Cardiomyoplasty was performed after training the LD muscle for four weeks. One week later the pacemaker was programmed in a DDD mode: amplitude 3.75 V, pulse duration 0.50 ms, AV delay 175 ms. The patient reached functional class grade I-II (NYHA). Inotrope support was discontinued and great clinical improvement was noted. The ejection fraction rose from 10% to 30%. Echocardiographic left ventricular outflow tract velocity increased from 0.33 m/s to 0.60 m/s. These values were compared with radionuclide angiocardiography and echocardiography evaluations. The great clinical improvement and positive changes in left ventricular parameters suggest that cardiomyoplasty is useful in the treatment of some cases of dilated or ischemic cardiomyopathy as an alternative to heart transplantation. Long term follow-up is necessary to evaluate this procedure.     

Combining transmural left ventricular mechanics and energetics to predict oxygen demand

This study relates to our earlier study which predicts the transmural distribution as well as the global left ventricular (LV) function and oxygen demand, based on the LV structure, geometry and sarcomere function. Here, we test the predicted global oxygen demand against experimental data in anesthetized, open chest dogs under changing working conditions. The experimental oxygen demand was calculated from the arterio-venous difference in oxygen content times the measured coronary flow. LV load was manipulated by a combination of a pressurized chamber connected to the femoral artery, phenylephrine infusion and an adjustable arteriovenous shunt. The heart was paced in two preset heart rates. The study demonstrates that the global predictions, based on the local distributed oxygen demand model, are comparable to those obtained by other methods of global metabolic predictions. However, unlike other global methods, the distributed model gives spatial information and predicts an endo/epi ratio of oxygen demand ranging between 1.05 to 1.14, depending on the loading conditions, which is comparable to available experimental data. For the experimental conditions studied here (stroke volume, heart rate, aortic pressure), the theoretical analysis shows that only the end diastolic volume is significantly correlated to the endo/epi ratio of the transmural oxygen demand. This study represents partial fulfillment of the requirements for the MD degree of S. Carasso in the Faculty of Medicine, the Technion-Israel Institute of Technology, Haifa, Israel.     

Cardiac cyclic nucleotides and norepinephrine during neural sympathetic stimulation

The role of the cardiac cyclic nucleotides, adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP), and norepinephrine (NE) in cardiac responses to stimulation of the left ansa subclavia were studied in anesthetized open-chest dogs. In three groups of dogs undergoing stimulation for 6 min with impulse frequencies of 4, 10, or 20 Hz and 5 V, left ventricular levels of cAMP, cGMP, and NE were determined at the end of the stimulation period and compared to control dogs. A significant elevation in cAMP (avg 67%) was found at all three frequencies. Myocardial NE decreased by an average of 58% from control by the end of the stimulation period, regardless of the stimulation frequency. The rate of left ventricular pressure rise (LV dP/dt) was found to be linearly related to the increase in myocardial cAMP (P less than 0.01) rather than to NE levels found after stimulation. Propranolol administered before ansa subclavia stimulation caused significant decreases in both cAMP and LV dP/dt, whereas the muscarinic agonist carbachol, caused increases in cGMP and NE and a decrease in LV dP/dt accompanied by a nonsignificant decline in cAMP. The elevation in levels of cGMP and NE and the decrease in LV dP/dt to carbachol were blocked with atropine. Results from pretreating dogs with propranolol and carbachol followed by neural sympathetic stimulation indicated the importance of beta-adrenergic and muscarinic receptors in modifying cardiac function through the production of the cyclic nucleotides. Sustained cardiac responses during ansa subclavia stimulation at physiological levels could be related to the accelerated synthesis of endogenous cAMP.     

In vivo validation of a novel method for regional myocardial wall motion analysis based on echocardiographic tissue tracking

The objective of this study was to validate a recently developed tissue tracking (TT) method for cardiac motion, by comparing it with precise invasive measurements of motion and to prove its capability to reflect moderate hemodynamic changes induced by asynchronous activation. In four open-chest sheep, sono-crystals measured the left ventricle(LV) equator’s diameters simultaneously with 2D ultrasound acquisition. The LV was paced either from the posterior or from the lateral wall, just prior to the normal LV activation. Global functional indices were calculated based on the regional motions extracted by the TT method. The correlation coefficient between the shortening of the diameters and the global circumferential strain (GCS) was 0.99 ± 0.004. The peak GCS differentiated between the pacing modes (paired t test, P < 0.05). The GCS, a measurement closely based on the TT method, followed the precise sono-crystals measurements and reflected moderate hemodynamic changes, thus providing a substantial proof of the TT method’s accuracy and clinical value.     

Optimization of Cardiac Fiber Orientation for Homogeneous Fiber Strain During Ejection

The strain of muscle fibers in the heart is likely to be distributed uniformly over the cardiac walls during the ejection period of the cardiac cycle. Mathematical models of left ventricular (LV) wall mechanics have shown that the distribution of fiber strain during ejection is sensitive to the orientation of muscle fibers in the wall. In the present study, we tested the hypothesis that fiber orientation in the LV wall is such that fiber strain during ejection is as homogeneous as possible. A finite-element model of LV wall mechanics was set up to compute the distribution of fiber strain at the beginning (BE) and end (EE) of the ejection period of the cardiac cycle, with respect to a middiastolic reference state. The distribution of fiber orientation over the LV wall, quantified by three parameters, was systematically varied to minimize regional differences in fiber shortening during ejection and in the average of fiber strain at BE and EE. A well-defined optimum in the distribution of fiber orientation was found which was not significantly different from anatomical measurements. After optimization, the average of fiber strain at BE and EE was 0.025 ± 0.011 (mean ± standard deviation) and the difference in fiber strain during ejection was 0.214 ± 0.018. The results indicate that the LV structure is designed for maximum homogeneity of fiber strain during ejection. © 1999 Biomedical Engineering Society. PAC99: 8719Hh, 8710+e, 8719Ff, 8719Rr, 0270Dh