Epicardial Layer Research Articles

Dioxin Inhibits Zebrafish Epicardium and Proepicardium Development

Embryonic exposure to the environmental contaminant and aryl hydrocarbon receptor agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), disrupts cardiac development and function in fish, birds, and mammals. In zebrafish, the temporal window of sensitivity to the cardiotoxic effects of TCDD coincides with epicardium formation. We hypothesized that this TCDD-induced heart failure results from disruption of epicardial development. To determine whether embryonic TCDD exposure inhibits epicardium and proepicardium (PE) development in zebrafish, we used histology and fluorescence immunocytochemistry to examine the epicardium formation in fish exposed to TCDD. TCDD exposure prevented epicardium formation. Using live imaging and in situ hybridization, we found that TCDD exposure blocked the formation of the PE cluster. In situ hybridization experiments showed that TCDD exposure also prevented the expression of the PE marker tcf21 at the site where the PE normally forms. TCDD also inhibited expansion of the epicardial layer across the developing heart: Exposure after PE formation was completed prevented further expansion of the epicardium. However, TCDD exposure did not affect epicardial cells already present. Because TCDD blocks epicardium formation, but is not directly toxic to the epicardium once complete, we propose that inhibition of epicardium formation can account for the window of sensitivity to TCDD cardiotoxicity in developing zebrafish. Epicardium development is crucial to heart development. Loss of this layer during development may account for most if not all of the TCDD-induced cardiotoxicity in zebrafish.

A computer model of endo-epicardial electrical dissociation and transmural conduction during atrial fibrillation

Structural alterations during atrial fibrillation (AF) not only lead to electrical dissociation within the epicardial layer, but also between the epicardial layer and the endocardial bundle network. The aim of the study was to investigate the role of transmural conduction in the stability of AF episodes using a dual-layer computer model. A proof-of-principle dual-layer model was developed in which connections between the layers can be introduced or removed at any time during the simulation. Using an S1-S2 protocol, a spiral wave was initiated in one of the layers, which degenerated into a complex AF pattern after connection with the other layer at six randomly chosen sites. After 6 s, connections were either retained (dual-layer simulations) or removed (single-layer simulations). Dual-layer simulations were more complex, as indicated by the higher number of waves and phase singularities. Tracking waves through both layers revealed that the number of waves in dual-layer simulations was significantly higher than in the single-layer simulations, reflecting more opportunities for reentry and a concomitant increase in AF stability. In the dual-layer model, only 12% of the AF episodes died out within 6 s, while 59% died out in the single-layer model. Atrial fibrillation patterns are more complex and AF episodes are more stable in a dual-layer model. This study indicates an important role for endo-epicardial conduction for the stabilization of AF.

Three-Dimensional Reconstruction of the Functional Strain-Line Pattern in the Left Ventricle From 3-Dimensional Echocardiography

Advances in 3-dimensional (3D) echocardiography offer a rapid, effective imaging technique with adequate temporal and spatial resolution for left ventricular motion assessment. 3D multidirectional tracking of the endocardial left ventricular layer has shown that the functional pattern of directional strain arrangement during cardiac contraction closely relates with the structural architecture of the myocardial helical muscle fiber orientation.1 In a similar manner, we carried out segmentation tracking of the endocardial-epicardial layers in 10 healthy young athletes (nonprofessional athletes, enrolled at the Sport Medicine Center of the University of Florence, Italy, training 2–3 days a week for 2 hours daily; all exhibiting an excellent echographic window) to evaluate the 3D strain pattern over the whole myocardium thickness and to compare with the hypothesized underlying fiber architecture. An echocardiographic 3D full-volume image of the left ventricular was recorded by a Philips IE33 machine (frame rate, 15–30 Hz). Imaging data were processed by 3D feature tracking (4DLVA 3.0; TomTec Gmbh, Unterschleissheim, Germany), and the endocardial and epicardial tracked surfaces were exported for the following principal strain analysis.1 Principal strain analysis allows to define the direction along which the main contractile strain (S1) develops, accompanied by a secondary strain (S2) that is typically of much …

Embolic complication of left ventricular non-compaction as an unusual cause of acute myocardial infarction

One of the greatest challenges in medicine consists of arriving at a correct diagnosis despite different presentations of the disease. We present a case in which, notwithstanding the initial diagnosis, the search for the etiology was essential for clinical guidance. Left ventricular non-compaction (LVNC) was first described by Chin et al. in 1990. This relatively new entity is characterized by excessive thickening of the myocardial wall, formed of a thin epicardial layer and a substantially thicker non-compacted endocardial layer. The clinical presentation is highly variable but it must always be borne in mind that heart failure, atrial and ventricular arrhythmias and embolic events are common complications of LVNC.

Embolic complication of left ventricular non-compaction as an unusual cause of acute myocardial infarction

One of the greatest challenges in medicine consists of arriving at a correct diagnosis despite different presentations of the disease. We present a case in which, notwithstanding the initial diagnosis, the search for the etiology was essential for clinical guidance. Left ventricular non-compaction (LVNC) was first described by Chin et al. in 1990. This relatively new entity is characterized by excessive thickening of the myocardial wall, formed of a thin epicardial layer and a substantially thicker non-compacted endocardial layer. The clinical presentation is highly variable but it must always be borne in mind that heart failure, atrial and ventricular arrhythmias and embolic events are common complications of LVNC.

THE STUDIES OF DIRECT TWO-DIMENSIONAL MEASUREMENTS, ANATOMICAL M-MODE METHOD, TISSUE VELOCITY IMAGING AND 2D SPECKLE TRACKING IMAGING TECHNOLOGY OF NORMAL MYOCARDIAL BIOMECHANICAL PARAMETERS AND THEIR RELATIONSHIP WITH CARDIAC FUNCTION

Objectives To investigate the methods of direct two-dimensional measurements, Anatomical M-mode method, Tissue Velocity Imaging and 2D Speckle Tracking technology in normal subject myocardial biomechanical parameters and their relationship with...

Epicardial management of myocarditis-related ventricular tachycardia

A 56-year-old patient who experienced a first-time syncope and a sustained monomorphic ventricular tachycardia (VT), treated with DC-shock, was documented ( Panel A ). Echocardiography and cardiac catheterization were unremarkable. Cardiac magnetic resonance imaging (CMR) revealed the presence of a delayed focal enhancement of gadolinium in the epicardial layer of the lateral wall and a normal left ventricular systolic function ( Panels …

Cardiac Regeneration from Activated Epicardium

In contrast to lower vertebrates, the mammalian heart has a very limited regenerative capacity. Cardiomyocytes, lost after ischemia, are replaced by fibroblasts. Although the human heart is able to form new cardiomyocytes throughout its lifespan, the efficiency of this phenomenon is not enough to substitute sufficient myocardial mass after an infarction. In contrast, zebrafish hearts regenerate through epicardial activation and initiation of myocardial proliferation. With this study we obtain insights into the activation and cellular contribution of the mammalian epicardium in response to ischemia. In a mouse myocardial infarction model we analyzed the spatio-temporal changes in expression of embryonic epicardial, EMT, and stem cell markers and the contribution of cells of the Wt1-lineage to the infarcted area. Though the integrity of the epicardial layer overlaying the infarct is lost immediately after the induction of the ischemia, it was found to be regenerated at three days post infarction. In this regenerated epicardium, the embryonic gene program is transiently re-expressed as well as proliferation. Concomitant with this activation, Wt1-lineage positive subepicardial mesenchyme is formed until two weeks post-infarction. These mesenchymal cells replace the cardiomyocytes lost due to the ischemia and contribute to the fibroblast population, myofibroblasts and coronary endothelium in the infarct, and later also to the cardiomyocyte population. We show that in mice, as in lower vertebrates, an endogenous, epicardium-dependent regenerative response to injury is induced. Although this regenerative response leads to the formation of new cardiomyocytes, their number is insufficient in mice but sufficient in lower vertebrates to replace lost cardiomyocytes. These molecular and cellular analyses provide basic knowledge essential for investigations on the regeneration of the mammalian heart aiming at epicardium-derived cells.

Association of Ventricular Noncompaction and Histiocytoid Cardiomyopathy: Case Report and Review of the Literature

We report an association between ventricular noncompaction and histiocytoid cardiomyopathy. Both entities are rare, and only 2 cases of their association have been reported previously in the medical literature. Ventricular noncompaction is believed to be caused by an arrest of the normal endomyocardial development, resulting in a thin and compacted epicardial layer and a thickened noncompacted endocardial layer. Histiocytoid cardiomyopathy is a rare arrhythmogenic disorder characterized by aggregates of oncocytic cells involving predominantly the subendocardium. These cells are thought to be abnormal Purkinje cells. In our case, the histiocytoid cells showed strong cytoplasmic expression for the skeletal muscle transcription factor MyoD1, which could be attributed to cross reactivity with an undetermined cytoplasmic antigen.

Quantitative Analysis of Endocardial and Epicardial Left Ventricular Myocardial Deformation—Comparison of Strain-Encoded Cardiac Magnetic Resonance Imaging with Two-Dimensional Speckle-Tracking Echocardiography

Quantitative analysis of segmental myocardial deformation of different myocardial layers has become possible using strain-encoded cardiac magnetic resonance imaging (SENC) and speckle-tracking echocardiography (STE). We evaluated and compared the quantitative analysis of myocardial deformation using SENC and STE. In 44 patients (age 61 ± 13 years, 34 men), SENC by cardiac magnetic resonance imaging using a 1.5-Tesla whole-body scanner and two-dimensional STE were performed prospectively. Quantitative layer-specific analysis of segmental left ventricular function was performed to determine the peak circumferential and peak longitudinal systolic strain values using SENC and STE of an endocardial and epicardial myocardial layer. In addition, segmental function was defined as normokinetic, hypokinetic, or akinetic by visual analysis of the magnetic resonance imaging cine sequences. The endocardial and epicardial strain defined by SENC or STE differed significantly between the visually defined segmental function states. The correlation of the peak circumferential endocardial strain by SENC versus STE (intraclass correlation coefficient [ICC] 0.493, 95% CI 0.358-0.597) tended to be better than the correlation of the circumferential epicardial strain using both methods (ICC 0.321, 95% CI 0.238-0.399). The correlation of the peak longitudinal endocardial strain by SENC and STE was similar (ICC 0.472, 95% CI 0.398-0.541), in contrast to the longitudinal epicardial strain analysis by both techniques (ICC 0.554, 95% CI 0.417-0.655). Circumferential strain analysis by STE allowed better distinction of the hypokinetic or akinetic segments from the normokinetic segments than did the circumferential strain analysis by SENC of the endocardial layer (area under the receiver operating characteristic curve [AUC ROC] 0.946 vs 0.884; P < .001) or epicardial layer (AUC ROC 0.884 vs 0.782; P < .001). Longitudinal strain analysis using STE and SENC of theendocardial layer (AUC ROC 0.851 vs 0.839; P= .5838) and epicardial layer (AUC ROC 0.849 vs 0.833; P= .4321) had similar diagnostic value for identifying the presence of hypokinetic and akinetic segments. Quantitative analysis of segmental deformation by SENC and STE allowed accurate distinction of myocardial segments with different functional states. Circumferential endocardial strain analysis by STE allowed the best distinction of segments with impaired function from the normokinetic segments.

Abstract 41: Explant-Derived Cells from Chronic Heart Failure Activated Endothelial-Mesenchymal Transition and Attenuated Pluripotency Genes Expression

Cardiac progenitor cells are generated from atria explants; however the cellular origin and the mechanisms of cell outgrowth are unclear. Using transgenic tamoxifen-induced Willms tumor 1 (Wt1)-Cre/ERT and Cre-activated GFP reporter mice, we found approximately 40% of explant-derived cells and 74% of explant-derived c-Kit+ cells originated from the epicardium. In atria from sham hearts, Wt1+ cells were located in a thin epicardial layer, while c-Kit+ cells were primarily found within both the sub-epicardium and the myocardium, albeit at low frequency. No overlap between c-Kit+ and Wt1+ cells was observed, suggesting that epicardial Wt1+ cells do not express c-Kit marker in vivo, but more likely the c-Kit marker was acquired in culture. Compared with 4 days in culture, at day 21 we observed 7 folds increase in Snail gene expression; 32% increase in α-smooth muscle actin (SMA) marker, and 30% decrease in E-cadherin marker, suggesting that the explant-derived cells underwent epithelial to mesenchymal transition (EMT) in vitro. Cell outgrowths released TGF-β (1036.4 ± 1.18 pm/ml) and exhibited active TGF-β signaling, which might triggered the EMT. Compared to shams, CHF cell outgrowths exhibited elevated levels of EMT markers, SMA (49% vs. 34%) and Snail (2 folds), and reduced level of Wt1 (11% vs. 22%). In addition, CHF cell outgrowths had two folds increase in Pai1 gene expression, a direct target of TGF-β signaling. In c-Kit+ cells derived from CHF explants, Nanog gene expression was 4 folds lower and Sox 2 was 2 folds lower compared with cells from shams. Suppression of EMT in cell outgrowth increased the percentage of c-Kit+ and Wt1+ cells by 17%, and 15%, respectively. Also suppression of EMT in c-Kit+ cells resulted in 4 folds increase in Nanog and 3 fold increase in Sox2 gene expressions. Our results showed that CHF may further exuberates EMT while diminishes the re-activation of pluripotency genes. Thus, EMT modulation in CHF is a possible strategy to regulate both the yield and the pluripotency of cardiac-explant-derived progenitor cells.

N-acetylcysteine prevents electrical remodeling and attenuates cellular hypertrophy in epicardial myocytes of rats with ascending aortic stenosis

Pressure overload is associated with cardiac hypertrophy and electrical remodeling. Here, we investigate the effects of the antioxidant N-acetylcysteine (NAC) on the cellular cardiac electrophysiology of female Sprague-Dawley rats with ascending aortic stenosis (AS). Rats were treated with NAC (1g/kg body weight) or control solution 1week before the intervention and in the week following AS or sham operation. Seven days after the operation, blood pressure and left ventricular pressure were measured before the heart was excised. Single cells were isolated from epicardial and endocardial layers of the left ventricular free wall and investigated using the whole-cell patch-clamp technique. Systolic blood pressure and left ventricular peak pressure were not significantly altered in the NAC group. NAC reduced the increase (p<0.001) in the relative left ventricular weight (p<0.05) as well as the increase (p<0.001) in cell capacitance in epicardial (p<0.05), but not in endocardial myocytes of AS animals. The L-type Ca(2+) current (I (CaL)) was significantly increased by AS in epicardial (+19% at 0mV, p<0.01) but not in endocardial myocytes. NAC completely prevented this increase in I (CaL) (p<0.01). The current density of the transient outward K(+) current (I (to)) was not affected by AS or NAC. Action potential duration to 90% repolarization was significantly prolonged in epicardial (p<0.01) as well as in endocardial (p<0.001) cells of AS animals. NAC prevented the AP prolongation in epicardial myocytes only (p<0.05). We conclude that reducing oxidative stress in pressure overload can prevent electrical remodeling and ameliorate hypertrophy in epicardial but not in endocardial myocytes.

Spatial variability in T-tubule and electrical remodeling of left ventricular epicardium in mouse hearts with transgenic Gαq overexpression-induced pathological hypertrophy

Pathological left ventricular hypertrophy (LVH) is consistently associated with prolongation of the ventricular action potentials. A number of previous studies, employing various experimental models of hypertrophy, have revealed marked differences in the effects of hypertrophy on action potential duration (APD) between myocytes from endocardial and epicardial layers of the LV free wall. It is not known, however, whether pathological LVH is also accompanied by redistribution of APD among myocytes from the same layer in the LV free wall. In the experiments here, LV epicardial action potential remodeling was examined in a mouse model of decompensated LVH, produced by cardiac-restricted transgenic Gαq overexpression. Confocal linescanning-based optical recordings of propagated action potentials from individual in situ cardiomyocytes across the outer layer of the anterior LV epicardium demonstrated spatially non-uniform action potential prolongation in transgenic hearts, giving rise to alterations in spatial dispersion of epicardial repolarization. Local density and distribution of anti-Cx43 mmune reactivity in Gαq hearts were unchanged compared to wild-type hearts, suggesting preservation of intercellular coupling. Confocal microscopy also revealed heterogeneous disorganization of T-tubules in epicardial cardiomyocytes in situ. These data provide evidence of the existence of significant electrical and structural heterogeneity within the LV epicardial layer of hearts with transgenic Gαq overexpression-induced hypertrophy, and further support the notion that a small portion of electrically well connected LV tissue can maintain dispersion of action potential duration through heterogeneity in the activities of sarcolemmal ionic currents that control repolarization. It remains to be examined whether other experimental models of pathological LVH, including pressure overload LVH, similarly exhibit alterations in T-tubule organization and/or dispersion of repolarization within distinct layers of LV myocardium.

Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination

Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 μM) and rotigaptide (RG, 0.1 μM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22-24% (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV(0) - D·κ (D, diffusion coefficient; LCV(0), LCV at κ = 0). CBX decreased LCV(0) and D by 27 ± 3 and 57 ± 3%, respectively (n = 5; P < 0.01). RG increased LCV(0) and D by 18 ± 3 and 54 ± 5%, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm(-1). SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.

LAYER-SPECIFIC ANALYSIS OF MYOCARDIAL DEFORMATION WITH 2D SPECKLE-TRACKING ECHOCARDIOGRAPHY FOR PREDICTION OF FUNCTIONAL RECOVERY IN ACUTE MYOCARDIAL INFARCTION

The capability of myocardial deformation (MD) analysis by 2D speckle-tracking echocardiography of an endocardial and an epicardial layer for prediction of functional recovery after acute myocardial infarction (AMI) was evaluated and compared to contrast-enhanced magnetic resonance imaging (ceMRI).

Increased aortic wave reflection and longitudinal regional diastolic dysfunction in patients with left ventricular hypertrophy

ObjectivesIncreased arterial stiffness is associated with the progression of left ventricular hypertrophy (LVH); however, the endocardial layer (End) contracts more than the epicardial layer (Epi), and it is unclear whether increased arterial stiffness affects regional wall deformation in both the End and Epi in LVH. MethodsWe performed echocardiography and measured the radial augmentation index (rAIx) in 41 patients with LVH. We evaluated the longitudinal strain, and early diastolic strain rate (SRdia) (measures of regional wall deformation) in both End and Epi in addition to measures of global diastolic function. The ratios of End strain to Epi strain (End/Epi strain) and End SRdia to Epi SRdia (End/Epi SRdia) were also calculated. ResultsAll of the patients had a decreased LV diastolic function (E/e′>8) and preserved ejection fraction (>45%). The rAIx was slightly related to the End/Epi SRdia (r=0.29, P=0.063); the relationship of rAIx to End/Epi SRdia (beta=0.52, P=0.034) was significant after adjustment for potential confounding factors. The rAIx at heart rate 75 beats per minute (rAIx@HR75) was significantly related to End/Epi SRdia (r=0.36, P=0.023); the relationship of rAIx@HR75 to End/Epi SRdia remained significant even after the adjustment (P=0.032). The relationships of rAIx@HR75 to End/Epi strain did not reach the level of statistical significance (r=0.30, P=0.06) in this study. ConclusionIncreased rAIx, a measure of aortic wave reflection, may be associated with a regional diastolic function in the ratio of endocardial to epicardial layer of the left ventricular wall in patients with left ventricular hypertrophy.

Intramural optical mapping of Vm and Cai2+ during long-duration ventricular fibrillation in canine hearts

Intramural gradients of intracellular Ca(2+) (Ca(i)(2+)) Ca(i)(2+) handling, Ca(i)(2+) oscillations, and Ca(i)(2+) transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Ca(i)(2+) handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Ca(i)(2+) handling contribute to LDVF, we measured membrane voltage (V(m)) and Ca(i)(2+) during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, V(m) and Ca(i)(2+) progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed V(m) upstrokes during pacing and LDVF. In conclusion, the fact that V(m) upstrokes always preceded CaTs indicates that spontaneous Ca(i)(2+) oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong V(m)-Ca(i)(2+) desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Ca(i)(2+) handling and may potentially contribute to LDVF maintenance.

Subendocardial contractile impairment in chronic ischemic myocardium: assessment by strain analysis of 3T tagged CMR.

BackgroundThe purpose of this study was to quantify myocardial strain on the subendocardial and epicardial layers of the left ventricle (LV) using tagged cardiovascular magnetic resonance (CMR) and to investigate the transmural degree of contractile impairment in the chronic ischemic myocardium.Methods3T tagged CMR was performed at rest in 12 patients with severe coronary artery disease who had been scheduled for coronary artery bypass grafting. Circumferential strain (C-strain) at end-systole on subendocardial and epicardial layers was measured using the short-axis tagged images of the LV and available software (Intag; Osirix). The myocardial segment was divided into stenotic and non-stenotic segments by invasive coronary angiography, and ischemic and non-ischemic segments by stress myocardial perfusion scintigraphy. The difference in C-strain between the two groups was analyzed using the Mann-Whitney U-test. The diagnostic capability of C-strain was analyzed using receiver operating characteristics analysis.ResultsThe absolute subendocardial C-strain was significantly lower for stenotic (-7.5 ± 12.6%) than non-stenotic segment (-18.8 ± 10.2%, p < 0.0001). There was no difference in epicardial C-strain between the two groups. Use of cutoff thresholds for subendocardial C-strain differentiated stenotic segments from non-stenotic segments with a sensitivity of 77%, a specificity of 70%, and areas under the curve (AUC) of 0.76. The absolute subendocardial C-strain was significantly lower for ischemic (-6.7 ± 13.1%) than non-ischemic segments (-21.6 ± 7.0%, p < 0.0001). The absolute epicardial C-strain was also significantly lower for ischemic (-5.1 ± 7.8%) than non-ischemic segments (-9.6 ± 9.1%, p < 0.05). Use of cutoff thresholds for subendocardial C-strain differentiated ischemic segments from non-ischemic segments with sensitivities of 86%, specificities of 84%, and AUC of 0.86.ConclusionsAnalysis of tagged CMR can non-invasively demonstrate predominant impairment of subendocardial strain in the chronic ischemic myocardium at rest.

Transmural Heterogeneity and Depressed Function in the Mechanical Properties of Ventricular Tissue from Patients with End-Stage Heart Failure

Heart failure is a progressive condition in which the ventricles can no longer pump enough blood to meet the body's basal demands. Our laboratory is investigating whether the transmural variation in cellular contractile properties that occurs in normal hearts (and which is thought to be important for ventricular function) is altered in heart failure. We procured through wall samples of failing left ventricle from patients receiving transplants at the University of Kentucky and non-failing samples from brain dead organ donors. The tissue was divided into epicardial, midmyocardial and endocardial layers and frozen in liquid nitrogen within 30 minutes. Multicellular chemically permeabilized preparations were subsequently obtained from these samples by mechanical homogenization and triton treatment. The samples were attached between a force transducer and a motor and subjected to two mechanical protocols: 1) a stretch-restretch protocol in solutions with different activating Ca2+ concentrations and 2) a force-velocity protocol in which maximally-activated preparations were allowed to shorten against pre-set loads. Parameters including steady-state force, short-range stiffness, short-range force and maximum power output were measured using these two protocols. The results suggested a 30% decrease in maximum power output (p-value = 0.01) and steady-state force (p-value=0.005) in heart failure patients (n=8, total of 72 preparations) as compared to non-failing (n=4, total of 36 preparations). Short-range stiffness (p-value=0.003) and short-range force (p-value=0.002) also significantly decreased in heart failure vs. non-failing. Transmurally there was a significant difference in maximum power output between the regions (p-value=0.02). The data suggests that mechanically the mid myocardium maybe affected the most in heart failure. Further studies need to be done to understand the protein modifications that may be responsible for these variations.

Evaluation of the Difference in Endocardial and Epicardial Layer Contraction Elucidated by 2D Speckle Tracking Imaging in Patients with Hypertension and Preserved Left Ventricular Ejection Fraction

Evaluation of the Difference in Endocardial and Epicardial Layer Contraction Elucidated by 2D Speckle Tracking Imaging in Patients with Hypertension and Preserved Left Ventricular Ejection Fraction