Contraction Delay Research Articles

Segmental anhidrosis and heat intolerance

A 62 year-old woman with no previous medical history presented to the Dermatology department with sweating disorders for several years. She described segmental hyperhidrosis and hyperemia while running. This excessive sweating occurred in the left hemiface, the left half of the trunk, the left upper limb and the right lower limb (Fig. 1A). This was associated with heat intolerance and previous faintness during sport. She did not describe any chest pain before faintness and the cardiac auscultation was normal. The neurological examination revealed a diffuse areflexia in the absence of any sensory or motor disorders. By illuminating the right eye, we observed a delay in ipsilateral pupillary contraction, whereas we observed an absence of the consensual photomotor reflex of the right eye by illuminating the left eye (Adie's tonic pupil, Fig. 1B and C, and Supplementary file 1). However, she did not complain of reduced visual acuity. Ross syndrome is a rare autonomic disorder caused by a selective degenerative process of the postganglionic cholinergic sudomotor neurons [[1]Sommer C. Lindenlaub T. Zillikens D. Toyka K.V. Naumann M. Selective loss of cholinergic sudomotor fibers causes anhidrosis in Ross syndrome.Ann Neurol. 2002; 52: 247-250Google Scholar]. Ross syndrome is diagnosed by the presence of a triad of symptoms associating segmental anhidrosis (with compensatory hyperhidrosis), Adie's tonic pupil and areflexia [[2]Mishra A.K. Kharkongor M. Kuriakose C.K. George A.A. Peter D. Carey R.A.B. et al.Is ross syndrome an autoimmune entity? A case series of 11 patients.Can J Neurol Sci. 2017; 44: 318-321Google Scholar]. The main complaint of patients is generally the segmental compensatory hyperhidrosis, the anhidrosis in contrast is not even noticed. The two other signs must be specifically examined for to make the diagnosis. The deep tendon hyporeflexia or areflexia affects the four limbs, whereas the tonic pupil is observed on the pathological and anhidrotic side of the face. It has been proposed to treat hyperhidrosis with botulinum toxin [[3]Bergmann I. Dauphin M. Naumann M. Flachenecker P. Müllges W. Koltzenburg M. et al.Selective degeneration of sudomotor fibers in Ross syndrome and successful treatment of compensatory hyperhidrosis with botulinum toxin.Muscle Nerve. 1998; 21: 1790-1793Google Scholar], but this treatment may theoretically increase the heat intolerance and the risk of faintness during sport. Even if the disorder is benign, the objective is to avoid any faintness. Clinicians should advise patients with Ross syndrome to wear light clothing for sports and to avoid excessive heat exposure.

Method for estimating tensiomyography parameters from motion capture data

Tensiomyography is a muscle performance assessment technique that measures its mechanical responses. In this study, we explore a possibility to replace traditional tensiomyography measurement system with motion capture. The proposed method allows for measurement of multiple muscle's points simultaneously, while achieving measurements during a patient's movements. The results show that approximately 5 mm error is achieved when estimating maximal muscle displacement, while time delay in muscle contraction and contraction time are assessed with upto 20 ms error. As confirmed by physicians, the introduced errors are with the acceptable margin and, thus, the obtained results are medically valid.

Optimal Swing Support During Walking Using Wireless Pneumatic Artificial Muscle Driver

This study evaluates the effect of swing support during walking using a wireless pneumatic artificial muscle (PAM) driver on hip and knee flexion angles. This driver can control two contraction parameters of the PAM: delay of contraction from the trigger and duration of contraction through a smartphone. Eleven healthy young individuals participated in this study. We asked the participants to walk with two PAMs attached to the left hip joint and a pressure sensor placed under the right heel to trigger the contraction. During the experiment, the contraction parameters were randomly changed: 0, 100, or 200 ms for the delay and 0, 100, 200, or 300 ms for the duration. The experimental results revealed significant differences in the hip and knee flexion angles, hip joint angular excursion, and stride length among the conditions. In addition, the optimal parameter differed among the subjects. It was confirmed that this individual variation was related to the walking speed of the subject, without PAM assistance.

Right ventricular function and dyssynchrony in Brugada syndrome: Highlighting the importance of the mechanical substrate in the right ventricular outflow tract

BackgroundCurrent evidence suggests that Brugada syndrome (BrS), far from being a purely electrical condition, is associated with subtle mechanical abnormalities primarily affecting the right ventricle (RV). We aimed to characterize RV function in BrS and investigate the echocardiographic profile of patients with arrhythmic events, with a special focus on parameters of RV dyssynchrony using speckle-tracking echocardiography (STE). MethodsAn echocardiogram was performed in 71 BrS patients and 25 healthy controls. STE was performed to assess regional and global RV mechanics, including RV outflow tract shortening (RVOTS). RVOT contraction time was considered to calculate the modified RV mechanical dispersion (RVMDm). Arrhythmic events were prospectively evaluated in the BrS cohort. ResultsCompared to controls, BrS patients showed subtle contractile abnormalities, including impaired RV longitudinal strain, higher RV index of myocardial performance (RIMP) and lower RVOTS. BrS patients also exhibited a greater contraction delay between the lateral and the septal aspect of the RV. After a median follow-up of 7.3 year (IQR 5.2–10.8), 6 patients presented malignant arrhythmic events. RIMP >0.50, RVOTS <16.2% and RVMDm > 42 ms showed high sensitivity for the identification of BrS patients with arrhythmic events during follow-up. ConclusionsSubtle RV mechanical abnormalities were present in BrS patients. RIMP and RVOTS, a novel STE-derived parameter, were found to be sensitive markers of arrhythmic events. Adding the RVOT contraction time to the analysis of RVMD may help identify patients at higher risk, reflecting the importance of the RVOT mechanical substrate in the assessment of the arrhythmic risk in BrS.

Electromechanical delay during functional electrical stimulation induced cycling is a function of lower limb position

Introduction Functional electrical stimulation (FES) induced cycling has been shown to be an effective rehabilitation for those with lower limb movement disorders. However, a consequence of FES is an electromechanical delay (EMD) existing between the stimulation input and the onset of muscle force. The objective of this study is to determine if the cycle crank angle has an effect on the EMD. Methods Experiments were performed on 10 participants, five healthy and five with neurological conditions resulting in movement disorders. A motor fixed the crank arm of a FES-cycle in 10° increments and at each angle stimulation was applied in a random sequence to a combination of the quadriceps femoris and gluteal muscle groups. The EMD was examined by considering the contraction delay (CD) and the residual delay (RD), where the CD (RD) is the time latency between the start (end) of stimulation and the onset (cessation) of torque. Two different measurements were used to examine the CD and RD. Further, two multiple linear regressions were performed on each measurement, one for the left and one for the right muscle groups. Results The crank angle was determined to be statistically relevant for both the CD and RD. Conclusions Since the crank angle has a significant effect on both the CD and RD, the angle has a significant effect on the EMD. Therefore, future efforts should consider the importance of the crank angle when modelling or estimating the EMD to improve control designs and ultimately improve rehabilitative treatments. Implications for rehabilitation New model predicts the delayed response of muscle torque production to electrical stimulation as a function of limb position during FES cycling. The model can inform closed-loop electrical stimulation induced rehabilitative cycling.

Mechanical-electrical interaction of the right ventricle in patients with repaired tetralogy of fallot: the next step towards resynchronization in congenital heart disease

Abstract Introduction Patients with repaired tetralogy of Fallot (rTF) and severe pulmonary regurgitation frequently progress to dilation and dysfunction of the right ventricle (RV). It has been documented in the literature that there is a correlation between the duration of the QRS in the surface electrocardiogram and the hemodynamic parameters of the RV of these patients, suggesting the presence of a mechanical-electrical interaction. Purpose To determine if there is an association between the contraction delay in certain areas of the RV measured in M-mode echocardiography and the delay in electrical activation measured in the electroanatomic map (EAM) of RV in patients with rTF. Methods Unicentric and observational study of all patients with rTF undergoing EAM, echocardiography with study of RV asynchrony and cardiac magnetic resonance imaging (MRI). Activation delay in the antero-basal area and in the RV outflow tract (RVOT) in the EAM were both analysed (Figure 1A). The shortening delay in the same areas in M-mode echocardiography was also evaluated (Figure 1B, C). MRI data regarding volume and ejection fraction was also collected. Results 64 patients were included (36.7±10.6 years, 65% men). The mean total activation time of the RV (RV-TAT) was 127.3±42.4 ms. Activation mapping showed a recurrent pattern with beginning in the interventricular septum and ending in RV antero-basal region and/or RVOT. A linear positive correlation was observed between RV-TAT and the activation delay in both regions analysed (ρ=0.60 and ρ=0.52, respectively; p&amp;lt;0.001) and also between the electrical and mechanical delay in the anterior wall (ρ=0.41; p=0.001). On the other hand, it was observed a negative correlation between RV ejection fraction (RVEF), measured on MRI, and the RV-TAT (ρ=−0.41, p=0.002) and also between RVEF and the activation delay in the RV antero-basal region and in the RVOT (ρ=−0.32, p=0.016 and ρ=−0.36, p=0.007, respectively). Conclusions There is a mechanical-electrical interaction in the RV of patients with rTF, with a negative correlation between the activation delay and RVEF and between mechanical and electrical activation delay in specific anatomical regions (regional mechanical-electrical interaction). These results may guide future studies on resynchronization in this heart disease. Figure 1. EAM and echocardiographic measures Funding Acknowledgement Type of funding source: None

Gene silencing of extracellular matrix protein 1 (ECM1) results in phenotypic alterations of dermal fibroblasts reminiscent of clinical features of lichen sclerosus

BackgroundLichen sclerosus (LS) is an acquired inflammatory mucocutaneous disease affecting the anogenital area, characterized histologically by hyalinosis and thickened vessel walls in the dermis. The presence of serum autoantibodies against extracellular matrix protein 1 (ECM1) in LS patients may suggest its involvement in disease pathogenesis. ObjectiveTo examine if reduced ECM1 production by dermal fibroblasts contributes to the pathogenic features of LS. MethodsGene expression in ECM1 knockdown human dermal fibroblasts was analyzed by cDNA microarray. Functional enrichment for genes involved in cellular functions was conducted. Protein expression was analyzed by ELISA and confocal laser scanning microscopy using LS skin. ResultsMicroarray analysis identified 3035 differentially expressed genes in ECM1 knockdown cells, wherein 1471 were upregulated genes related exclusively to cell adhesion, proliferation, apoptosis, intracellular signaling, and extracellular matrix organization. Further narrowing with criteria specific for localization and function of ECM1 identified 48 upregulated genes identified to have structural, fibrogenic, and carcinogenic properties. Of these, laminin-332 and collagen-IV displayed altered immunolabeling within the basement membrane zone (BMZ) and dermal vessels in LS skin, similar to that of collagen-VII, which exhibited unchanged transcription levels in ECM1-knockdown fibroblasts. Collagen-VII bound to recombinant ECM1 in a solid-phase immunoassay and colocalized with ECM1 in the skin BMZ. Further, ECM1-knockdown fibroblasts exhibited a marked delay in cell migration and gel contraction. ConclusionIn the absence of ECM1 expression in fibroblasts there is selective dysregulation and disassembly of structural and extracellular matrix molecules, which may result in microstructural abnormalities reminiscent of LS.

The impact of right bundle branch block on right ventricular size and function assessed by three-dimensional speckle-tracking echocardiography.

To determine the influence of right bundle branch block (RBBB) on right ventricular (RV) size and function, we investigated the association between complete RBBB (CRBBB) and RV volume, function, and dyssynchrony by three-dimensional echocardiography. In this retrospective, cross-sectional study, 103 consecutive patients with adequate three-dimensional echocardiographic images were divided into the CRBBB, middle-range QRS, and narrow QRS group. RV volumetric and functional data were compared between the three groups. Among the 103 patients (44.8 ± 18.7years, 50 men), the CRBBB group comprised 26 (25%) patients and the middle-range QRS group comprised 48 (47%). The CRBBB group showed a significant contraction delay in the RV inlet free wall and outflow tract; larger RV end-diastolic and systolic volume index (RV-EDVI, RV-ESVI); and lower RV systolic function. On dividing the CRBBB patients into two (with or without mechanical dyssynchrony), those with RV dyssynchrony showed larger RV-EDVI (121 ± 45 vs. 85 ± 25 mL/m2, P = 0.019) and RV-ESVI (93 ± 42 vs. 56 ± 20 mL/m2, P = 0.009) and smaller RV ejection fraction (24 ± 11 and 34 ± 11%, P = 0.026) than those without RV dyssynchrony. RV dyssynchrony in CRBBB patients might have an adverse effect on RV volume and function. Three-dimensional speckle-tracking echocardiography could provide additional and beneficial data during assessment of RV dyssynchrony.

A new method to recommend left ventricular lead positions for improved CRT volumetric response and long-term prognosis

ObjectivesUsing ECG-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), we sought to develop and validate a new method to recommend left ventricular (LV) lead positions in order to improve volumetric response and long-term prognosis after cardiac resynchronization therapy (CRT). MethodsSeventy-nine patients received gated SPECT MPI at baseline, and echocardiography at baseline and follow-up. The volumetric response referred to a reduction of ≥ 15% in LV end-systolic volume 6 months after CRT. After excluding apical, septal, and scarred segments, there were three levels of recommended segments: (1) the optimal recommendation: the latest contracting viable segment; (2) the 2nd recommendation: the late contracting viable segments whose contraction delays were within 10° of the optimal recommendation; and (3) the 3rd recommendation: the viable segments adjacent to the optimal recommendation when there was no late contracting viable segment. ResultsAfter excluding 11 patients whose LV lead was placed in apical or scarred segments, 75.6% of the patients concordant to recommended LV segments (n = 41) responded to CRT while 51.9% of those with non-recommended LV lead locations (n = 27) were responders (P = .043). Response rates were 76.9%, 76.9%, and 73.3% (P = .967), respectively, when LV lead was implanted in the optimal recommendation (n = 13), the 2nd recommendation (n = 13), and the 3rd recommendation (n = 15). LV leads placed at recommended segments reduced composite events of all-cause mortality or heart failure (HF) rehospitalization compared with pacing at non-recommended segments (log-rank χ2 = 5.623, P = .018). ConclusionsPacing in the recommended LV lead segments identified on gated SPECT MPI was associated with improved volumetric response to CRT and long-term prognosis.

Echocardiographic assessment of ventricular contraction and synchrony in children with isolated complete atrioventricular block and epicardial pacing: Implications of interventricular mechanical delay.

To assess the correlations between interventricular mechanical delay (IVMD) and cardiac function in children with isolated complete atrioventricular block and epicardial pacing. We enrolled 13 children (six boys) with an epicardial dual-chamber pacemaker due to isolated complete or advanced atrioventricular block. The patients were 9.8 (range, 6.8-15.3) years old, and none had symptomatic heart failure at the follow-up visit. Ventricular pacing sites, which remained the same for 7.2 (1.6-12.3) years, were the left ventricle (LV) in two patients, right ventricle (RV) in four patients, and both ventricles in seven patients. IVMD was ≤40ms in six patients (short IVMD group) and >40ms in seven patients (long IVMD group). Compared with the long IVMD group, the short IVMD group was associated with better LV longitudinal strain (-20% [-24% to -18%] vs -16% [-20% to -13%], P<.05). The short IVMD group had superior LV mechanical synchrony than the long IVMD group (septal to lateral delay of the time to peak longitudinal strain 15 [-16-78] ms vs 78 [13-93] ms, P<.05; standard deviation of the time to peak radial strain 13 [9-34] ms vs 35 [18-64] ms, P<.05). In children with epicardial pacing at LV, RV, or both ventricles, a left-sided contraction delay was associated with poorer LV contraction and impaired LV synchrony. IVMD will help to stratify patients during follow-up.

Peristaltic-Like Motion of the Human Fetal Right Ventricle and its Effects on Fluid Dynamics and Energy Dynamics.

In both adult human and canine, the cardiac right ventricle (RV) is known to exhibit a peristaltic-like motion, where RV sinus (inflow region) contracts first and the infundibulum (outflow region) later, in a wave-like contraction motion. The delay in contraction between the sinus and infundibulum averaged at 15% of the cardiac cycle and was estimated to produce an intra-ventricular pressure difference of 15mmHg. However, whether such a contractile motion occurs in human fetuses as well, its effects on hemodynamics remains unknown, and are the subject of the current study. Hemodynamic studies of fetal hearts are important as previous works showed that healthy cardiac development is sensitive to fluid mechanical forces. We performed 4D clinical ultrasound imaging on eight 20-weeks old human fetuses. In five fetal RVs, peristaltic-like contractile motion from the sinus to infundibulum ("forward peristaltic-like motion") was observed, but in one RV, peristaltic-like motion was observed from the infundibulum to sinus ("reversed peristaltic-like motion"), and two RVs contraction delay could not be determined due to poor regression fit. Next, we performed dynamic-mesh computational fluid dynamics simulations with varying extents of peristaltic-like motions for three of the eight RVs. Results showed that the peristaltic-like motion did not affect flow patterns significantly, but had significant influence on energy dynamics: increasing extent of forward peristaltic-like motion reduced the energy required for movement of fluid out of the heart during systolic ejection, while increasing extent of reversed peristaltic-like motion increased the required energy. It is currently unclear whether the peristaltic-like motion is an adaptation to reduce physiological energy expenditure, or merely an artefact of the cardiac developmental process.

Right ventricular dyssynchrony in pulmonary hypertension: Phase analysis using FDG-PET imaging

BackgroundRight ventricular (RV) performance in patients of pulmonary hypertension (PH) requires optimal assessment. The objective of this study is to develop phase analysis using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging as a feasible tool for evaluation of RV dyssynchrony in PH. Methods and ResultsFifty-four PH patients with well-characterized hemodynamic parameters were enrolled. All subjects performed FDG-PET imaging for RV phase analysis and RV function evaluation. Two-dimensional echocardiography with speckle tracking analysis was conducted to obtain RV time to peak systolic strain (PSST) as a comparison. The median contraction delay difference between RV middle free wall and septum measured by PET phase analysis (RVPDPET) was 20.12° (interquartile range, 4.99°-30.10°). The median difference of PSST between RV middle free wall and middle septal wall (RVPDEcho) measured by echocardiography was 43.98° (interquartile range, 6.25°-72.00°). RVPDPET was well correlated with RVPDEcho (r = 0.685, P < .001). RV phase standard deviation (RVSD) and histogram bandwidth (RVBW) derived from PET phase histogram were significantly correlated with cardiac index, RV ejection fraction, 6-minute walking distance, and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) (RVSD: r = −0.532, P < .001; r = −0.551, P < .001; r = −0.544, P < .001; r = 0.404, P < .01; respectively, RVBW: r = −0.492, P < .001; r = −0.466, P < .001; r = −0.544, P < .001; r = 0.349, P = .01, respectively), while there were no significant correlations between RVSD and RVBW with hemodynamic parameters (right atrial pressure, right ventricular systolic pressure, right ventricular end-diastolic pressure, mean pulmonary artery pressure, and total pulmonary resistance). ConclusionsContraction delays between RV free wall and septum in PH measured by phase analysis and speckle tracking echocardiography were well correlated. RV dyssynchrony measured by phase analysis of FDG-PET was significantly related to RV dysfunction. Phase analysis of FDG-PET is feasible to evaluate RV mechanical dyssynchrony in patients of PH.

Development and validation of a phase analysis tool to measure interventricular mechanical dyssynchrony from gated SPECT MPI

ObjectivesThe purpose of this study is to develop a right-ventricular (RV) phase analysis tool which when coupled with our left ventricular (LV) phase analysis tool can provide measurement of the interventricular mechanical dyssynchrony from gated SPECT myocardial perfusion imaging (MPI), and validate the tool by electrocardiography (ECG). MethodsFor each patient, short-axis LV and RV SPECT MPI images were input into an automatic sampling algorithm to generate the 3D maximal count circumferential profiles for both LV and RV in each cardiac frame. Subsequently, the samples of LV and RV were separately used by our phase analysis tool based on the first-harmonic Fourier approximation to calculate the contraction onset for each sample. The difference between contraction onsets of the middle LV free wall and middle LV septal wall represented the LV contraction delay; the difference between contraction onsets of the middle RV free wall and middle RV septal wall represented the RV contraction delay. The difference between the LV and RV contraction delays represented the interventricular contraction delay, which was compared with the interventricular conduction delay classified by ECG to validate the concordance of interventricular mechanical and electrical dyssynchrony. Sixty-one bundle branch block (BBB) patients with ischemic-dilated cardiomyopathy (26, 42.6%) or non-ischemic-dilated cardiomyopathy (35, 57.4%), who underwent 12-lead surface ECG and gated resting Tc-99m sestamibi SPECT, were retrospectively analyzed in this study. ResultsIn the 30 patients with left bundle branch block (LBBB) by ECG, there were 27 patients whose LV contracted later than the RV according to SPECT; and in the 31 patients with right bundle branch block (RBBB) by ECG, there were 26 patients whose LV contracted earlier than the RV according to SPECT. In total, an agreement rate of 86.9% (53 of 61) was achieved between SPECT and ECG. The Kappa agreement rate was 73.8% (95% confidence interval 0.57-0.91). ConclusionThe preliminary results showed promise for the measurement of interventricular mechanical dyssynchrony in BBB patients with dilated cardiomyopathy using our phase analysis tool.

Relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging and cardiac reverse remodeling levels after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) can provide cardiac reverse remodeling (RR), which may include mechanical reverse remodeling (MRR) and/or electrical reverse remodeling (ERR). However, uncoupling of MRR and ERR is not uncommon, and the underlying mechanisms are not clear. This study aimed to evaluate the relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging (MPI) and cardiac RR post-CRT. Forty-one patients (26 men, mean age 66±10years) with heart failure received CRT for at least 12months were assigned to three groups according to their levels of RR: I, MRR+ERR (ESV reduced ≥15% and intrinsic QRS duration reduced ≥10ms); II, MRR only (ESV reduced ≥15%); and III, non-responder (the others). All the patients also underwent MPI under transient CRT-off to evaluate the intrinsic myocardial substrates, including myocardial scar, LV volumes and function, systolic dyssynchrony, and activation sequences. In addition, ventricular tachycardia (VT) and ventricular fibrillation (VF) detected by the CRT devices during follow-up periods were also recorded. Quantitative analysis of MPI showed that there were significant differences for scar burden [15.9±9.5, 26.8±16.1, and 45.6±15.1% for group I (n=15), II (n=16), and III (n=10), respectively, p<0.001], EDV (136.6±64.9, 221.6±123.9, and 351.8±216.3ml, p=0.002), ESV (82.6±59.8, 172.3±117.2, and 293.3±209.6ml, p=0.001), LVEF (44.9±15.0, 25.6±10.9, and 21.5±11.7%, p<0.001), systolic phase SD (23.4°±10.3°, 36.0°±16.2°, and 57.0°±22.2°, p<0.001), and bandwidth (72.5°±31.1°, 113.4°±56.4°, and 199.1°±90.1°, p<0.001). Myocardial scar interfered with the normal propagation of mechanical activation, resulting in heterogeneous activation sequences. Compared with group II (MRR only), group I (ERR+MRR) had significantly less initial activation segments (1.9±1.0 vs. 2.6±0.7, p<0.05) and shorter maximal contraction delay (46.9°±12.9° vs. 58.8°±18.5°, p<0.05). During the periods of follow-up, 21 patients developed VT/VF, including only 1 patient (1 VT) in group I (6.7%), 8 patients (7 VT and 1 VF) in group II (50%), and 9 patients (7 VT and 5 VF) in group III (90%). The characteristics of myocardial substrates as assessed by MPI differed significantly between different levels of cardiac RR post-CRT. Myocardial scar played an important role in the development of ERR. Different cardiac RR levels contributed to different incidences of ventricular arrhythmia, and the combination of ERR and MRR provided highest anti-arrhythmic effects.

Consequences of intravascular lymphatic valve properties: a study of contraction timing in a multi-lymphangion model.

The observed properties of valves in collecting lymphatic vessels include transmural pressure-dependent bias to the open state and hysteresis. The bias may reduce resistance to flow when the vessel is functioning as a conduit. However, lymphatic pumping implies a streamwise increase in mean pressure across each valve, suggesting that the bias is then potentially unhelpful. Lymph pumping by a model of several collecting lymphatic vessel segments (lymphangions) in series, which incorporated these properties, was investigated under conditions of adverse pressure difference while varying the refractory period between active muscular contractions and the inter-lymphangion contraction delay. It was found that many combinations of the timing parameters and the adverse pressure difference led to one or more intermediate valves remaining open instead of switching between open and closed states during repetitive contraction cycles. Cyclic valve switching was reliably indicated if the mean pressure in a lymphangion over a cycle was higher than that in the lymphangion upstream, but either lack of or very brief valve closure could cause mean pressure to be lower downstream. Widely separated combinations of refractory period and delay time were found to produce the greatest flow-rate for a given pressure difference. The efficiency of pumping was always maximized by a long refractory period and lymphangion contraction starting when the contraction of the lymphangion immediately upstream was peaking. By means of an ex vivo experiment, it was verified that intermediate valves in a chain of pumping lymphangions can remain open, while the lymphangions on either side of the open valve continue to execute contractions.

The effect of alternating current stimulation on the esophageal motility of rabbits

Objective To observe the effect of electrical stimulation on the movement of rabbits esophagus, and to promote effective esophageal peristalsis and determine the best electrical pacing parameters. Methods After anesthesia, 24 healthy rabbits underwent open surgery and the lower esophagus was exposed. The esophagus was stimulated with the multi-channel signal generator, and the changes of esophagus pressure and the length of esophageal contraction with high resolution manometry were recorded.(1) The effects on contraction pressure of esophagus body and lower esophageal sphincter (LES) after single site electrical stimulation under different parameters were observed.The stimulation modes utilized were electric current 3 mA, 5 mA and 8 mA, frequency 5 Hz, 10 Hz and 20 Hz, pulsewidth 0.25 ms, 25 ms and 50 ms, waveform of single phase and double phase.(2)The esophagus was sequentially stimulated. The stimulation mode utilized was electric current 5 mA, frequency 20 Hz, pulsewidth 25 ms, stimulation duration 3 s, single phase square wave. Results At electrical stimulation on the esophagus body and LES, contraction delay was 13.00±1.54 ms and 12.00±0.73 ms respectively. The contraction pressure of esophageal body was significantly positively related tothe electric current (R=0.968, P<0.01), the pulse width(R=0.971, P<0.01), and the frequency (R=0.947, P<0.01). The length of contraction in 10 Hz group was shorter than that of the 20 Hz group(1.33±0.06 cm VS 1.80±0.00 cm, P<0.05). The contraction pressure of LES was also significantly positively related to the electric current(R=0.965, P<0.01), the pulse width (R=0.973, P<0.01), and the frequency (R=0.842, P<0.01). The pressure of lower esophageal sphincter of single phase square wave was greater than that of the double phase square group (P<0.05). Under the same parameters, the contraction pressure of LES group was lower than that of the esophageal body group (27.33±1.15 mmHg VS 104.00±6.00 mmHg, P<0.05). Esophageal sequential contraction was induced by multi-points sequential electrical stimulation. Conclusion Single point electric stimulation can cause esophageal contraction immediately without obvious delay. Within a certain range, the esophageal contraction pressure is positively correlated with electric current, frequency and pulse width. The contraction pressure of single square phase wave is greater than that of the double square phase wave. The contraction pressure of esophageal body is greater than that of LES after electric stimulation. Multi-points sequential electrical stimulation can promote sequential movement of esophagus. Key words: Electrostimulation; Achalasia; Gastroesophageal reflux; High resolution manometry; Low esophageal sphincter

Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix

Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported collagen gels that create lateral boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix.

Recoordination of opposing walls drives the response to cardiac resynchronization therapy: a longitudinal study using a strain discoordination index.

Intraventricular dyssynchrony has traditionally been studied by means of contraction delays between different myocardial segments. Recently, the discoordination of opposing wall contraction throughout the cardiac cycle has been proposed as a more faithful predictor of response. Aim of the current study was to evaluate which parameters - mechanical dyssynchrony or discoordination - normalize with left ventricular response to cardiac resynchronization therapy (CRT). Cardiac mechanics were analysed before and after 6 months of CRT in 53 patients with left bundle branch block and advanced heart failure. Discoordination was quantified by means of the transverse strain discoordination index (TSDI) at basal and mid-ventricular segments; this index takes into account the percentage of time in the cardiac cycle in which cardiac deformation (transverse strain) of the two opposing walls occurs in noncoordinated directions. Dyssynchrony indices included septal to lateral peak-to-peak transverse strain delay and the standard deviation of time to peak tissue velocity in 12 mid-basal segments (Yu index). Around 63% of patients met the response criteria. Several baseline indices were predictive of reverse remodelling; TSDI at the mid-ventricular level demonstrated the best accuracy. Time from Q to peak velocity and strain tended to increase in all explored myocardial segments; despite a trend towards a decrease in septal-to-lateral strain delay, the latter decreased equally in responders and in nonresponding patients. Yu index decreased in responders more than in nonresponders, with borderline significance. Basal and medium TSDI remained unchanged in nonresponders and consistently normalized in patients who responded to CRT. The changes in TSDI were significantly correlated with improvements in left ventricular end-systolic volume and ejection fraction; the strongest correlation was observed for changes in TSDI measured at the mid-ventricular level. Left ventricular reverse remodelling after CRT is accompanied by the recoordination of opposite-wall contraction, as testified by changes in mid-ventricular TSDI, which also reveals as a very good predictor of response. On the contrary, changes of segmental peak-to-peak delays (dyssynchrony indices) fail to capture the complex nature of left ventricular response to CRT.

Simulation studies of circular muscle contraction, longitudinal muscle shortening, and their coordination in esophageal transport.

On the basis of a fully coupled active musculomechanical model for esophageal transport, we aimed to find the roles of circular muscle (CM) contraction and longitudinal muscle (LM) shortening in esophageal transport, and the influence of their coordination. Two groups of studies were conducted using a computational model. In the first group, bolus transport with only CM contraction, only LM shortening, or both was simulated. Overall features and detailed information on pressure and the cross-sectional area (CSA) of mucosal and the two muscle layers were analyzed. In the second group, bolus transport with varying delay in CM contraction or LM shortening was simulated. The effect of delay on esophageal transport was studied. For cases showing abnormal transport, pressure and CSA were further analyzed. CM contraction by itself was sufficient to transport bolus, but LM shortening by itself was not. CM contraction decreased the CSA and the radius of the muscle layer locally, but LM shortening increased the CSA. Synchronized CM contraction and LM shortening led to overlapping of muscle CSA and pressure peaks. Advancing LM shortening adversely influenced bolus transport, whereas lagging LM shortening was irrelevant to bolus transport. In conclusion, CM contraction generates high squeezing pressure, which plays a primary role in esophageal transport. LM shortening increases muscle CSA, which helps to strengthen CM contraction. Advancing LM shortening decreases esophageal distensibility in the bolus region. Lagging LM shortening no longer helps esophageal transport. Synchronized CM contraction and LM shortening seems to be most effective for esophageal transport.

Abstract 20350: Discordant Left Bundle Branch Block is Associated With Left Ventricular Dyssyncrhony at Cardiac Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy

LBBB is frequently linked to left ventricular (LV) dyssynchrony and adverse prognosis in HF. LBBB has been defined as concordant (cLBBB) or discordant (dLBBB), when associated in lead I and V5, V6 with a positive or negative T wave respectively. dLBBB has been associated with a worse clinical and prognostic profile in HF patients. We sought to evaluate association between different patterns of LV dV/dT curves at CMR, LBBB morphology, clinical correlates and prognostic role in patients with nonischemic systolic HF. Methods and Results: One hundred and fifteen consecutive patients with LBBB were submitted between 2004 and 2014 to a complete cardiological evaluation, including CMR with analysis of dV/dT curves of LV contraction, and follow-up for cardiac events. We distinguished two different patterns of global and segmental LV systole: a “narrow” pattern (NP) generated by synchronous contraction of wall segments; a “wide” pattern (WP), when delay in contraction between wall segments resulted in a prolungation of systolic peak with a flat or notched morphology. Fourteen patients presenting with normal LV dimensions and function all had cLBBB and NP, while out of 101 patients with HF, those with dLBBB (65%) presented with shorter QRS duration (p &lt; .01) and higher level of NT-proBNP (p &lt; .001). WP was observed more frequent in dLBBB patients (p &lt; .003) as a mark of greater intraventricular dyssynchrony. According to systolic pattern, those with WP had higher levels of NT-proBNP, lower EF and higher LV volumes than those with NP, whereas no significant difference was found in QRS duration. At multivariate analysis only dLBBB (p=.006) and EF (p=.001) were independent predictors of WP. At Kaplan-Meier analysis, the presence of WP was associated with a worse prognosis considering a composite end-point of cardiac death, hospitalization for HF and ICD shock (p&lt;.005). At Cox analysis only presence of WP (p = .029) and level of NT-proBNP (p= .004) were independent predictors. Conclusions: In nonischemic systolic HF patients with LBBB, presence of a WP at CMR dV/dT curves is associated with dLBBB, identifies greater LV dyssynchrony with possible major benefits from resynchronization therapy and is an independent prognosticator.