Left ventricle longitudinal strain of the endocardial and epicardial layers and left ventricle remodelling in children born with low and extremely low body weight aged from one to five years old

Background. In last decades, the number of babies born preterm has increased significantly. Premature newborns are more susceptible to cardiovascular disease in the long-term. To identify subclinical myocardial impairment in premature infants, an assessment of of the left ventricle (LV) deformation could be used.Objective. The aim of the study was to study the left ventricle (LV) Longitudinal Strain of the endocardial, middle and epicBardial layers in children born with very low and extremely low body weight, at the age from one to five years.Design and methods. The study included 88 children aged from one to 5 years old, born very premature with very low and extremely low body weight. The comparison group consisted of 43 healthy children of the same age, born full-term. The LV Longitudinal Strain of the endocardial, middle and epicardial layers was studied using the Speckle Tracking Imaging-2D Strain.Results. In children aged 1 to 5 years, born with very low and extremely low body weight, changes in the gradient of transmural wall Strain and a decrease in LV segments longitudinal strain were detected in 15.90 % and 14.77 % of cases, respectively. Mothers of children born prematurely and who subsequently registered disturbance of the transmural gradient of left ventricular strain in 10 cases (71.43 %) had a history of threatened termination of pregnancy. The threat of termination of pregnancy was noted in all women whose children had a decrease in LV segmental strain. In children who have normal of LV segmental strain, the threat of termination of pregnancy in mothers was registered in 16 cases (26.23 %). LV remodeling is observed in children with a change in the gradient of transmural wall strain or and with a decrease in LV longitudinal segment strain. Conclusion. Changes in the transmural gradient of wall deformation or reduction of segmental LV deformation in the longitudinal direction in premature infants require correction of the conventional algorithm of dispensary observation in an outpatient setting.

Cardiovascular risk is associated with a transmural gradient of myocardial oxygenation during adenosine infusion

Aims In patients with coronary artery disease (CAD), a transmural gradient of myocardial perfusion has been repeatedly observed, with the subendocardial layer showing more pronounced perfusion deficits. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) allows for monitoring transmural changes of myocardial oxygenation in vivo. We hypothesized that OS-CMR could help identify a transmural oxygenation gradient as a disease marker in patients at risk for CAD. Methods and results We assessed 34 patients with known CAD and 28 subjects with coronary risk factors but no evidence of significant CAD. Results were compared with 11 healthy volunteers. OS-CMR was performed at 1.5 T, applying a T2*-weighted cine steady state free precession sequence at baseline and during infusion of adenosine. A reader blinded to patient data quantified the relative change of myocardial oxygenation in OS-CMR, defined by the change of signal intensity (ΔSI%) between baseline and during adenosine infusion in the entire myocardium, the subepicardial layer, and the subendocardial layer. SI changes were homogenous throughout the myocardium in healthy subjects, whereas both, patients with risk factors only and patients with CAD, had a significantly smaller ΔSI% in the subendocardial layer than in the subendocardial layer. Both patient groups had an overall decreased ΔSI% across all layers when compared with healthy subjects (P < 0.05). Conclusion Even in the absence of overt CAD, cardiovascular risk factors are associated with a transmural gradient of the myocardial oxygenation response to adenosine as assessed by OS-CMR. An inducible transmural oxygenation gradient may serve as a non-invasive marker for cardiovascular risk.

The Effects of Load on Transmural Differences in Contraction of Isolated Mouse Ventricular Cardiomyocytes

Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of load upon transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various loads were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Extent of the transmural gradient in the time course of contractions was independent of the loading conditions where unloaded and heavy loaded (isometric) contractions were examined, but the regional gradient of the relaxation time characteristics tended to decrease when the load decreased. Under auxotonic contractions, time to peak contraction (Tmax) was significantly longer in ENDO cells than in EPI cells at low preload. An increase in preload (axial stretch) prolonged Tmax in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in transmural gradient in Tmax at high preload. The [Ca2+]i transient decay time constant was consistent with the greater preload dependency in Tmax of EPI cells. Our modified mathematical models reproduced experimental results, suggesting that differences in cooperativity of cross bridges and calcium troponin C complex interactions between the ENDO and EPI cardiomyocytes may contribute to the different cellular responses to stretch, which may provide a decrease in transmural dispersion of cellular shortening in the intact heart.

Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1–S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution ( Smax) > 1 ( P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope −1.36 ± 1.9 and −0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic.

Variable t-tubule organization and Ca2+ homeostasis across the atria

Although t-tubules have traditionally been thought to be absent in atrial cardiomyocytes, recent studies have suggested that t-tubules exist in the atria of large mammals. However, it is unclear whether regional differences in t-tubule organization exist that define cardiomyocyte function across the atria. We sought to investigate regional t-tubule density in pig and rat atria and the consequences for cardiomyocyte Ca2+ homeostasis. We observed t-tubules in approximately one-third of rat atrial cardiomyocytes, in both tissue cryosections and isolated cardiomyocytes. In a minority (≈10%) of atrial cardiomyocytes, the t-tubular network was well organized, with a transverse structure resembling that of ventricular cardiomyocytes. In both rat and pig atrial tissue, we observed higher t-tubule density in the epicardium than in the endocardium. Consistent with high variability in the distribution of t-tubules and Ca2+ channels among cells, L-type Ca2+ current amplitude was also highly variable and steeply dependent on capacitance and t-tubule density. Accordingly, Ca2+ transients showed great variability in Ca2+ release synchrony. Simultaneous imaging of the cell membrane and Ca2+ transients confirmed t-tubule functionality. Results from mathematical modeling indicated that a transmural gradient in t-tubule organization and Ca2+ release kinetics supports synchronization of contraction across the atrial wall and may underlie transmural differences in the refractory period. In conclusion, our results indicate that t-tubule density is highly variable across the atria. We propose that higher t-tubule density in cells localized in the epicardium may promote synchronization of contraction across the atrial wall.

Does the combination of hyperkalemia and KATP activation determine excitation rate gradient and electrical failure in the globally ischemic fibrillating heart?

Ventricular fibrillation (VF) in the globally ischemic heart is characterized by a progressive electrical depression manifested as a decline in the VF excitation rate (VFR) and loss of excitability, which occur first in the subepicardium (Epi) and spread to the subendocardium (Endo). Early electrical failure is detrimental to successful defibrillation and resuscitation during cardiac arrest. Hyperkalemia and/or the activation of ATP-sensitive K+ (KATP) channels have been implicated in electrical failure, but the role of these factors in ischemic VF is poorly understood. We determined the VFR-extracellular K+ concentration ([K+]o) relationship in the Endo and Epi of the left ventricle during VF in globally ischemic hearts (Isch group) and normoxic hearts subjected to hyperkalemia (HighK group) or a combination of hyperkalemia and the KATP channel opener cromakalim (HighK-Crom group). In the Isch group, Endo and Epi values of [K+]o and VFR were compared in the early (0–6 min), middle (7–13 min), and late (14–20 min) phases of ischemic VF. A significant transmural gradient in VFR (Endo > Epi) was observed in all three phases, whereas a significant transmural gradient in [K+]o (Epi > Endo) occurred only in the late phase of ischemic VF. In the Isch group, the VFR decrease and inexcitability started to occur at much lower [K+]o than in the HighK group, especially in the Epi. Combining KATP activation with hyperkalemia only shifted the VFR-[K+]o curve upward (an effect opposite to real ischemia) without changing the [K+]o threshold for asystole. We conclude that hyperkalemia and/or KATP activation cannot adequately explain the heterogeneous electrical depression and electrical failure during ischemic VF.