Transmural Layers Research Articles

Four-dimensional Cardiac Modelling of Multiphase Computed Tomography for Predicting Outcomes After Transcatheter Aortic Valve Replacement.

Multiphase computed tomography angiography (mpCTA) is routinely performed prior to transcatheter aortic valve replacement (TAVR) to determine eligibility and enable preprocedural planning. Incremental prognostic value may be realized from full-cycle, multiphase reconstructions to assess the contractile health of the cardiac chambers. In this study we assessed the feasibility of 4-dimensional chamber modelling of the left ventricle (LV) to support 3-dimensional minimum principal strain (3DminPS)-based predictions of clinical outcomes after TAVR. Two hundred five patients undergoing pre-TAVR mpCTA were studied. UNet-based 3D chamber segmentation was followed by mesh modelling and 3D feature tracking-based deformation to determine global 3DminPS for endocardial, epicardial, and transmural layers. Independent associations of 3DminPS with the primary outcome of heart failure hospitalization or death are described. Of the 205 patients studied, 196 (96%) had analyzable mpCTAs (median age, 85 years; 55% male; Society of Thoracic Surgeons Predicted Risk of Mortality score= 3.10; 60.0% echocardiographic LV ejection fraction). At a median of 25 months after TAVR, 55 patients (28%) experienced the primary outcome. After adjustment for baseline variables, patients with an endocardial 3DminPS amplitude worse than-23.7% experienced a 2.7-fold higher risk of the outcome (adjusted hazard ratio, 2.7; 95% confidence interval, 1.4-5.1; P= 0.001), with this high-risk cohort having 1- and 3-year event rates of 32% and 49%, respectively. Four-dimensional chamber modelling of mpCTA using UNet-based segmentation and standardized mesh deformation is feasible and enables delivery of 3D deformation markers with strong prognostic value for the prediction of outcomes after TAVR. Prospective validation in a multicentre setting is currently being undertaken.

Abstract 10325: Feasibility and Predictive Utility of Three-Dimensional Myocardial Deformation Analysis From Multi-Phase Computed Tomography Angiography in Transcatheter Aortic Valve Replacement

Introduction : Multi-phase computed tomography angiography (CTA) for the pre-procedural planning of TAVR presents a unique opportunity to assess 3D myocardial biomechanics. Using a novel approach, we assessed the feasibility and predictive utility of 3D myocardial deformation analysis (3D-MDA) to deliver principal strain (PS) based markers of left ventricular (LV) health for the prediction of time to heart failure hospitalization or death following TAVR. Methods: 205 patients undergoing a pre-TAVR CTA and followed clinically for >6 months were identified. Whole-heart segmentation with 3D-mesh modelling was followed by 3D-MDA of the LV. 3D global LV minimum PS (minPS) was calculated for endocardial, epicardial and transmural layers. Cox regression models were performed to evaluate associations between 3D minPS and the composite outcome of all-cause mortality or heart failure hospitalization. Results: Of 205 patients, 196 (96%) had analyzable CTA data for 3D-MDA. Median (IQR) age was 85 (79.5-88) years (55% male) with median STS-PROM score 3.10 (2.10-4.55)% and median echocardiography LVEF 60 (55.9-65.0)%. Over 25 (11-36) months 55 patients (28%) experienced all-cause death or HF hospitalization. Patients with lower 3D minPS, below -23.7%, experienced a 3-fold increased risk of the primary outcome (p<0.001). Following adjustment for baseline characteristics, inclusive of STS and LVEF, 3D minPS remained independently associated with the primary outcome: endocardial 3D minPS providing highest prognostic value [HR (95% CI) of 1.09 per 1% change (1.04-1.15), p<0.001]. Conclusions: 3D-MDA of pre-TAVR multi-phase CTA is feasible and delivers principal-strain based markers strongly predictive of future clinical outcomes. The potential of this approach to optimize patient selection and post-procedural management requires future evaluation in a multi-centre setting.

A Closed-Loop Modeling Framework for Cardiac-to-Coronary Coupling.

The mechanisms by which cardiac mechanics effect coronary perfusion (cardiac-to-coronary coupling) remain incompletely understood. Several coronary models have been proposed to deepen our understanding of coronary hemodynamics, but possibilities for in-depth studies on cardiac-to-coronary coupling are limited as mechanical properties like myocardial stress and strain are most often neglected. To overcome this limitation, a mathematical model of coronary mechanics and hemodynamics was implemented in the previously published multi-scale CircAdapt model of the closed-loop cardiovascular system. The coronary model consisted of a relatively simple one-dimensional network of the major conduit arteries and veins as well as a lumped parameter model with three transmural layers for the microcirculation. Intramyocardial pressure was assumed to arise from transmission of ventricular cavity pressure into the myocardial wall as well as myocardial stiffness, based on global pump mechanics and local myofiber mechanics. Model-predicted waveforms of global epicardial flow velocity, as well as of intramyocardial flow and diameter were qualitatively and quantitatively compared with reported data. Versatility of the model was demonstrated in a case study of aortic valve stenosis. The reference simulation correctly described the phasic pattern of coronary flow velocity, arterial flow impediment, and intramyocardial differences in coronary flow and diameter. Predicted retrograde flow during early systole in aortic valve stenosis was in agreement with measurements obtained in patients. In conclusion, we presented a powerful multi-scale modeling framework that enables realistic simulation of coronary mechanics and hemodynamics. This modeling framework can be used as a research platform for in-depth studies of cardiac-to-coronary coupling, enabling study of the effect of abnormal myocardial tissue properties on coronary hemodynamics.

Transmural recordings of gastrointestinal electrical activity using a spatially-dense microelectrode array

Objective. High-resolution serosal recordings provide detailed information about the bioelectrical conduction patterns in the gastrointestinal (GI) tract. However, equivalent knowledge about the electrical activity through the GI tract wall remains largely unknown. This study aims to capture and quantify the bioelectrical activity across the wall of the GI tract. Approach. A needle-based microelectrode array was used to measure the bioelectrical activity across the GI wall in vivo. Quantitative and qualitative evaluations of transmural slow wave characteristics were carried out in comparison to the serosal slow wave features, through which the period, amplitude, and SNR metrics were quantified and statistically compared. Main results. Identical periods of 4.7 ± 0.3 s with amplitudes of 0.17 ± 0.04 mV versus 0.31 ± 0.1 mV and signal to noise ratios of 5.5 ± 1.3 dB versus 14.4 ± 1.1 dB were observed for transmural and serosal layers, respectively. Four different slow wave morphologies were observed across the transmural layers of the GI wall. Similar amplitudes were observed for all morphology types, and Type 1 and Type 2 were of the highest prevalence, dominating the outer and inner layers. Type 2 was exclusive to the middle layer while Type 4 was primarily observed in the middle layer as well. Significance. This study demonstrates the validity of new methodologies for measuring transmural slow wave activation in the GI wall and can now be applied to investigate the source and origin of GI dysrhythmias leading to dysmotility, and to validate novel therapeutics for GI health and disease.

An organosynthetic dynamic heart model with enhanced biomimicry guided by cardiac diffusion tensor imaging.

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle. The heart model is composed of organic endocardial tissue from a preserved explanted heart with intact intracardiac structures and an active synthetic myocardium that drives the motion of the heart. Inspired by the helical ventricular myocardial band theory, we used diffusion tensor magnetic resonance imaging and tractography of an unraveled organic myocardial band to guide the design of individual soft robotic actuators in a synthetic myocardial band. The active soft tissue mimic was adhered to the organic endocardial tissue in a helical fashion using a custom-designed adhesive to form a flexible, conformable, and watertight organosynthetic interface. The resulting biorobotic hybrid heart simulates the contractile motion of the native heart, compared with in vivo and in silico heart models. In summary, we demonstrate a unique approach fabricating a biomimetic heart model with faithful representation of cardiac motion and endocardial tissue anatomy. These innovations represent important advances toward the unmet need for a high-fidelity in vitro cardiac simulator for preclinical testing of intracardiac devices.

Myocardial blood flow analysis of stress dynamic myocardial CT perfusion for hemodynamically significant coronary artery disease diagnosis: The clinical value of relative parameter optimization

BackgroundThe methods for calculating the optimal myocardial blood flow (MBF) relative parameters in stress dynamic myocardial CT perfusion (CTP) in the detection of hemodynamically significant coronary artery disease (CAD) are non-uniform and lack standards. MethodsA total of 86 patients who were prospectively recruited underwent APT stress dynamic myocardial CTP. The relative MBF perfusion parameters were calculated as av_Ratio, Q3av_Ratio and hi_Ratio according to the three types of reference MBF values, respectively: (1) average segmental MBF value, (2) the third quartile of the average segmental MBF value, and (3) highest segmental MBF value. All the data were derived from both the endocardial and transmural layers of the myocardium. Invasive coronary angiography and fractional flow reserve (ICA/FFR) were used as the reference standards for myocardial ischemia evaluation. ResultsA total of 151 vessels of 60 patients (43 men and 17 women; 61.38 ± 8.01 years) were enrolled in the analysis. The performance of the endocardial layer was superior to that of the transmural layer (all P < 0.05). The hi_Ratio of the endocardial myocardium (AUC = 0.906, 95% CI: 0.857–0.954), for which the highest segmental value was selected as the reference MBF, was superior to both av_Ratio and Q3av_Ratio for ischemia detection (AUC, 0.906 vs.0.879, P < 0.05; 0.906 vs.0.891, P = 0.18), and the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 74.1%, 93.6%, 87.8%, 85.3% and 86.1%, respectively. The cutoff value of hi_Ratio was 0.675. ConclusionsThe relative MBF parameter of the endocardial myocardium using the highest segmental MBF value as a reference provided optimal diagnostic accuracy for the detection of hemodynamically significant CAD.

Differential Effects of Isoproterenol on Regional Myocardial Mechanics in Rat Using Three-Dimensional Cine DENSE Cardiovascular Magnetic Resonance

The present study assessed the acute effects of isoproterenol on left ventricular (LV) mechanics in healthy rats with the hypothesis that β-adrenergic stimulation influences the mechanics of different myocardial regions of the LV wall in different ways. To accomplish this, magnetic resonance images were obtained in the LV of healthy rats with or without isoproterenol infusion. The LV contours were divided into basal, midventricular, and apical regions. Additionally, the midventricular myocardium was divided into three transmural layers with each layer partitioned into four segments (i.e., septal, inferior, lateral, and anterior). Peak systolic strains and torsion were quantified for each region. Isoproterenol significantly increased peak systolic radial strain and circumferential-longitudinal (CL) shear strain, as well as ventricular torsion, throughout the basal, midventricle, and apical regions. In the midventricle, isoproterenol significantly increased peak systolic radial strain, and induced significant increases in peak systolic circumferential strain and longitudinal strain in the septum. Isoproterenol consistently increased peak systolic CL shear strain in all midventricular segments. Ventricular torsion was significantly increased in nearly all segments except the inferior subendocardium. The effects of isoproterenol on LV systolic mechanics (i.e., three-dimensional (3D) strains and torsion) in healthy rats depend on the region. This region dependency is also strain component-specific. These results provide insight into the regional response of LV mechanics to β-adrenergic stimulation in rats and could act as a baseline for future studies on subclinical abnormalities associated with the inotropic response in heart disease.

Effect of hydromorphone postconditioning on electrophysiological stability during ischemia-reperfusion in isolated rat hearts

Objective To evaluate the effect of hydromorphone postconditioning on the electrophysiological stability during ischemia-reperfusion (I/R) in isolated rat hearts. Methods Healthy adult male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were heparinized and anesthetized with pentobarbital sodium.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃.Twenty-four Langendorff-perfused hearts were divided into 3 groups (n=8 each) using a random number table: control group (group C), I/R group and hydromorphone postconditioning group (group HM). The isolated hearts were subjected to 60 min ischemia followed by 60 min reperfusion to establish the model of isolated heart I/R injury.The isolated hearts were perfused with K-H solution containing 4.1 ng/ml hydromorphone for 10 min starting from onset of reperfusion in group HM.Heart rate, electrocardiogram, coronary flow, and monophasic action potential amplitude, in the left ventricular endocardium, mid-myocardium and epicardium the maximal increase rate (Vmax) at the 0 phase, and monophasic action potential duration at 50% and 90% repolarization (MAPD50 and MAPD90, respectively) were recorded at 20 min of stabilization (T0) and 10, 25, 40 and 60 min of reperfusion (T1-4). The transmural dispersion of repolarization (TDR) was calculated, and the time for restoration of spontaneous heart beat was recorded. Results There was no significant difference in the heart rate, coronary flow or monophasic action potential amplitude between the three groups (P>0.05). Compared with group C, Vmax in the epicardium was significantly decreased, MAPD50 and MAPD90 in the three transmural layers were prolonged, and TDR was prolonged in group I/R (P 0.05). Conclusion Hydromorphone postconditioning is helpful in maintaining the electrophysiological stability during I/R in isolated rat hearts. Key words: Hydromorphone; Myocardial reperfusion injury; Cardiac electrophysiology; Ischemic postconditioning

Regional quantification of myocardial mechanics in rat using 3D cine DENSE cardiovascular magnetic resonance.

Rat models have assumed an increasingly important role in cardiac research. However, a detailed profile of regional cardiac mechanics, such as strains and torsion, is lacking for rats. We hypothesized that healthy rat left ventricles (LVs) exhibit regional differences in cardiac mechanics, which are part of normal function. In this study, images of the LV were obtained with 3D cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance in 10 healthy rats. To evaluate regional cardiac mechanics, the LV was divided into basal, mid-ventricular, and apical regions. The myocardium at the mid-LV was further partitioned into four wall segments (i.e. septal, inferior, lateral, and anterior) and three transmural layers (i.e. sub-endocardium, mid-myocardium, and sub-epicardium). The six Lagrangian strain components (i.e. Err , Ecc , Ell , Ecl , Erl , and Ecr ) were computed from the 3D displacement field and averaged within each region of interest. Torsion was quantified using the circumferential-longitudinal shear angle. While peak systolic Ecl differed between the mid-ventricle and apex, the other five components of peak systolic strain were similar across the base, mid-ventricle, and apex. In the mid-LV myocardium, Ecc decreased gradually from the sub-endocardial to the sub-epicardial layer. Ell demonstrated significant differences between the four wall segments, with the largest magnitude in the inferior segment. Err was uniform among the four wall segments. Ecl varied along the transmural direction and among wall segments, whereas Erl differed only among the wall segments. Erc was not associated with significant variations. Torsion also varied along the transmural direction and among wall segments. These results provide fundamental insights into the regional contractile function of healthy rat hearts, and form the foundation for future studies on regional changes induced by disease or treatments.

Computational Investigation of Transmural Differences in Left Ventricular Contractility.

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.

Heterogeneity of Fractional Anisotropy and Mean Diffusivity Measurements by In Vivo Diffusion Tensor Imaging in Normal Human Hearts.

BackgroundCardiac diffusion tensor imaging (cDTI) by cardiovascular magnetic resonance has the potential to assess microstructural changes through measures of fractional anisotropy (FA) and mean diffusivity (MD). However, normal variation in regional and transmural FA and MD is not well described.MethodsTwenty normal subjects were scanned using an optimised cDTI sequence at 3T in systole. FA and MD were quantified in 3 transmural layers and 4 regional myocardial walls.ResultsFA was higher in the mesocardium (0.46 ±0.04) than the endocardium (0.40 ±0.04, p≤0.001) and epicardium (0.39 ±0.04, p≤0.001). On regional analysis, the FA in the septum was greater than the lateral wall (0.44 ±0.03 vs 0.40 ±0.05 p = 0.04). There was a transmural gradient in MD increasing towards the endocardium (epicardium 0.87 ±0.07 vs endocardium 0.91 ±0.08×10-3 mm2/s, p = 0.04). With the lateral wall (0.87 ± 0.08×10-3 mm2/s) as the reference, the MD was higher in the anterior wall (0.92 ±0.08×10-3 mm2/s, p = 0.016) and septum (0.92 ±0.07×10-3 mm2/s, p = 0.028). Transmurally the signal to noise ratio (SNR) was greatest in the mesocardium (14.5 ±2.5 vs endocardium 13.1 ±2.2, p<0.001; vs epicardium 12.0 ± 2.4, p<0.001) and regionally in the septum (16.0 ±3.4 vs lateral wall 11.5 ± 1.5, p<0.001). Transmural analysis suggested a relative reduction in the rate of change in helical angle (HA) within the mesocardium.ConclusionsIn vivo FA and MD measurements in normal human heart are heterogeneous, varying significantly transmurally and regionally. Contributors to this heterogeneity are many, complex and interactive, but include SNR, variations in cardiac microstructure, partial volume effects and strain. These data indicate that the potential clinical use of FA and MD would require measurement standardisation by myocardial region and layer, unless pathological changes substantially exceed the normal variation identified.

Abstract 20355: Cardiac Magnetic Resonance Assessment of Absolute Myocardial Blood Flow and Myocardial Perfusion Reserve Compared With FFR in Patients With Coronary Artery Disease

Background: The diagnostic value of absolute myocardial blood flow (AMBF) obtained by cardiac magnetic resonance (CMR) quantitative measurement remains uncertain. We evaluated the subendocardial, epicardial, transmural AMBF, and myocardial perfusion reserve (MPR) derived from AMBF determined by perfusion CMR. We also assessed the relationship between CMR-derived AMBF and fractional flow reserve (FFR) in patients with coronary artery disease (CAD). Methods and Results: We investigated 38 CAD patients (mean age, 67±10 years; male, 89%, 46 vessels territories) who underwent perfusion CMR both at stress and rest, and invasive coronary angiography. FFR was measured in all vessels with stenosis more than 40% by QCA. FFR&lt;0.8 was considered hemodynamically significant stenosis. Patients with previous revascularization and/or myocardial infarction, and with renal dysfunction were excluded. We perform quantitative analysis of the transmural, subendocardial and epicardial AMBF, and MPR at mid-ventricular level. AMBF distributed in the wide range both subendocardium and subepicardium. At stress, AMBF was significantly increased in all of the subendocardial, epicardial, and transmural layers of the ischemic segment at adenosine-induced hyperemia from rest AMBF. (At rest: subendocardial 245±122 ml/100g/min, epicardial 124 [75-233] ml/100g/min, transmural 172 [102-261] ml/100mg/min. At stress: subendocardial 380 [156-517] ml/100g/min, epicardial 275 [158-502] ml/100g/mintransmural 287 [152-456] ml/100g/min.) There was a significant relationship between transmural AMBF and FFR, transmural MPR and FFR values, with r = 0.33 (p = 0.028), r=0.39 (p=0.007). The transmural MPR&lt;2.47 threshold yielded a sensitivity of 0.92 (95% confidence interval: 0.77 to 0.99) and a specificity of 0.71 (0.44-0.90) to detect coronary ischemia with a FFR &lt;0.8, and an area under the ROC curve (AUC) of 0.77 (0.62 to 0.88) for vessel-based analysis. Subendocardial AMBF and MPR gradually decreased with decreasing FFR at ischemic segment, but it was not significant. Conclusions: The quantitative analysis of transmural AMBF and myocardial MPR on perfusion cardiac magnetic resonance may predicts hemodynamically significant CAD as defined by FFR.

Acute intestinal obstruction with granulomas in the serosa

A 74-year-old man visited our hospital with complaints of abdominal discomfort and diarrhea. Upper gastrointestinal endoscopy and colonoscopy showed no evidence of disease that could explain his symptoms. He had a medical history of inguinal hernia repair by laparoscopic surgery five years ago and blood transfusion treatments for obscure gastrointestinal bleeding (OGIB) two years ago. Since some unknown small intestinal disease was suspected, capsule endoscopy was performed with a patency capsule used prior to the capsule endoscopy. At 54 hours after the capsule ingestion, he developed ileus. Computed tomography showed obstruction of the small intestine around the right inguinal region, and the patency capsule remained in the proximal extended small intestine. Ileo─jejunal resection with re-anastomosis was performed at 75 hours after the capsule ingestion. The stenosis was hard and measured 1 cm. The patency capsule was not incarcerated and had not dissolved. Histopathological (hematoxylin-eosin staining) examination showed infiltration of lymphocytes in the transmural layers within the limits of the stenosis, and to our surprise, multiple granulomas infiltrating the serosa, although the result of acid-fast bacterial staining was negative. There were no abnormal findings of the vessel walls. There are several case reports of paravesical granulomas whose formation is triggered by foreign bodies several years after inguinal hernia repair. In this case, the intestinal stenosis was adjacent to the narrow space between the adhesive cord and the abdominal wall. We thought that temporary and repeated incarcerations of the small intestine into that narrow space may have been responsible for the severe stenosis with granulomas in the serosa and the chronic ischemic inflammation of the intestine.

Partial Uncoupling of Impulse Source to Atrial Tissue by Ablation Triggers De Novo Ectopic Beats Through Paradoxical Improvement of Impulse Propagation

Background A source-sink mechanism plays a crucial role in transmission of electrical impulse to tissue. We hypothesized that partial uncoupling of impulse source to tissue by ablation might generate ectopic beats. Methods Canine right atrial preparations (n = 5) were coronary perfused and optically mapped using ANBDQBS, a near-infrared voltage-sensitive dye, to assess the origin and spread of excitation in transmural layers. The sinus node (SN) and surrounding atrial tissue in the field of view were reconstructed after Masson-trichrome, H&E, and immunofluorescence. Masson-trichrome histology was merged with the optical mapping. Cryoablation at –70°C for >3 minutes was performed in the SN and the atrial tissue. Results At baseline, sinus impulse originated from a specific cluster of the histologically demarcated SN (n = 5, 124 ± 23 bpm). Random extensive cryoablation on the SN and atrial tissue caused de novo activation of the ectopic foci outside the field of view (n = 3/5). We also observed the ectopic focus outside the histologic SN independently producing only spontaneous electrical oscillatory waves at baseline before ablation (n = 1), which was composed of HCN4 + cells in immunohistochemistry. However, this isolated electrical activity failed to propagate to the large atrium, as evidenced by the inability of this cluster to generate P waves on the pseudo-ECG. We created partial uncoupling of the nonpropagated ectopic source to the large atrium by cryoablation. In contrast to preablation, the nonpropagated ectopic source acquired the ability to propagate to the surviving atrial myocardium and generated ectopic beats. Conclusions The current study suggests that incomplete ablation may induce ectopic beats through paradoxical improvement of impulse conduction to the cardiac tissue by reducing coupling of impulse source to atrial sink. The current study may provide a mechanistic insight and clinical implications on generation of ectopic beats.

Electromechanical coupling in cardiomyocytes from transmural layers of guinea pig left ventricle

The electrical and mechanical activity of heart ventricle cardiomyocytes is known to vary depending on the spatial location of cells in the wall, in particular, transmurally from the sub-endocardial layer to the sub-epicardial one. To investigate intracellular mechanisms of the functional heterogeneity of cardiomyocytes we developed mathematical models of the electromechanical coupling in cardiomyocytes from different transmural layers across the left ventricle (LV) wall of guinea pig. It is shown that the mechanisms of both direct linkages and feedback in the electromechanical coupling contribute to differences in both the shape and duration of action potential, and speed characteristics of contraction between isolated cardiac myocytes from the sub-endocardial and sub-epicardial layers.

Reprint of: The paradox of α-adrenergic coronary vasoconstriction revisited

Activation of coronary vascular α-adrenoceptors results in vasoconstriction which competes with metabolic vasodilation during sympathetic activation. Epicardial conduit vessel constriction is largely mediated by α(1)-adrenoceptors; the constriction of the resistive microcirculation largely by α(2)-adrenoceptors, but also by α(1)-adrenoceptors. There is no firm evidence that α-adrenergic coronary vasoconstriction exerts a beneficial effect on transmural blood flow distribution. In fact, α-blockade in anesthetized and conscious dogs improves blood flow to all transmural layers, during normoperfusion and hypoperfusion. Also, in patients with coronary artery disease, blockade of α(1)- and α(2)-adrenoceptors improves coronary blood flow, myocardial function and metabolism. This article is part of a Special Issue entitled "Coronary Blood Flow".

Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

BackgroundMyocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM.Methods and resultsA stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium −34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6%) and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°). Reproducibility of FA was superior to MD (p = 0.003). Global MD was significantly higher in the septum than the reference lateral wall (0.784 ± 0.188 vs 0.750 ± 0.154 x10-3 mm2/s, p < 0.001). Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from −8.3° to −10.4°, all p < 0.001).ConclusionsTo the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation.

Challenging cardiac electrophysiology

Challenging cardiac electrophysiology

Echocardiographic study of left ventricular transmural radial displacement during acute myocardial ischemia and left ventricular pacing in vivo: a canine model

Objective To evaluate the changes of peak segmental and transmural radial displacement (RD) of left ventricle(LV) during acute myocardial ischemia with different LV pacing patterns. Methods Left anterior descending coronary artery (LAD) was ligated to induce acute myocardial ischemia in open-chest Beagle canine models ( n=10). Two-dimensional gray-scale images with overlaid tissue Doppler velocity imaging in three standard LV short-axis views were acquired with different pacing patterns in a randomized sequence in three complete cardiac cycles. Parameters including peak RD, peak RD time(RD-Tc) ,the standard deviation of TC(RD-TSD) of 12 segments and their myocardial layers(subend,mid,subepi) were measured and analyzed using TDI-Q workstation. Results ① There were no significant differences of peak RD between three myocardial layers of LV wall in each different pacing pattern group;There were no significant difference of peak RD from segments and transmural layers among the different LV pacing patterns. ②With acute myocardial ischemia the RD correlation of LV lateral pacing( LVL-P) and LV border pacing(LVB-P) patterns were higher than that of LV apical pacing(LVA-P) pattern between global segment and its subend, mid, subepi. ③ RD-Tc of 12 LV segments and their subend, mid, subepi appeared after T wave and there were no significant differences of RD-Tc among different LV pacing patterns. ④RD-TSD of the corresponding segments during LVL-P,LVA-P and LVB-P patterns were significant lower than those during acute yocardial ischemia(P<0. 05). Conclusions The existed RD correlation of LVA-P between subend.mid, subepi and the segment were lowest among the different ischemic LV pacing patterns; the synchronization of transmural RD could be recovered partly with LVL-P, LVA-P and LVB-P patterns. The echocardiographic study of LV transmural RD might be useful to reveal the segmental and the transmural myocardial mechanical state with different LV pacing patterns during acute ischemia in detail. Key words: Echocardiography; Myocardial ischemia; Ventricular function, left Displacement

Transmural optical measurements of V m dynamics during long-duration ventricular fibrillation in canine hearts

Knowledge of transmural V(m) changes is important for understanding the mechanism of long-duration ventricular fibrillation (LDVF). The purpose of this study was to measure transmural V(m) changes during LDVF. V(m) was recorded optically at up to 8 transmural points separated by 1.5 mm in the left ventricle of Langendorff-perfused canine hearts (n = 6) using a bundle of optical fibers (optrode) during 10 minutes of LDVF followed by 3 minutes of VF with reperfusion. Measurements were grouped into 4 layers: epicardium, subepicardium, midwall, and subendocardium. Activation rates (ARs) and action potential durations (APDs) decreased, whereas diastolic intervals (DIs) increased during LDVF in all transmural layers (P < .05). After approximately 3 minutes of LDVF, ARs were faster and DIs shorter in the midwall and subendocardium than in the epicardium and subepicardium (P < .05). Activations persisted at the subendocardium but disappeared from other layers after approximately 8 minutes of VF in the majority of hearts. There were no transmural differences in APD during LDVF or during pacing before and after LDVF (P > .05). Restitution plots showed no functional relationship between APD and DI in any layer at any stage of LDVF. Partial reperfusion during VF for 3 minutes restored transmural synchronicity of activation and eliminated gradients in activation parameters. V(m) dynamics evolve differently at different transmural layers. The subendocardium maintains persistent and the fastest activation during 10 minutes of LDVF, suggesting it contains the source of VF wavefronts. There are no transmural APD gradients and no restitution relationship between APD and DI at any transmural layer, indicating these are not the primary factors in the mechanism of LDVF.