Contraction Wave Velocity Research Articles

Effects of gap junction inhibition on contraction waves in the murine small intestine in relation to coupled oscillator theory

Waves of contraction in the small intestine correlate with slow waves generated by the myenteric network of interstitial cells of Cajal. Coupled oscillator theory has been used to explain steplike gradients in the frequency (frequency plateaux) of contraction waves along the length of the small intestine. Inhibition of gap junction coupling between oscillators should lead to predictable effects on these plateaux and the wave dislocation (wave drop) phenomena associated with their boundaries. It is these predictions that we wished to test. We used a novel multicamera diameter-mapping system to measure contraction along 25- to 30-cm lengths of murine small intestine. There were typically two to three plateaux per length of intestine. Dislocations could be limited to the wavefronts immediately about the terminated wave, giving the appearance of a three-pronged fork, i.e., a fork dislocation; additionally, localized decreases in velocity developed across a number of wavefronts, ending with the terminated wave, which could appear as a fork, i.e., slip dislocations. The gap junction inhibitor carbenoxolone increased the number of plateaux and dislocations and decreased contraction wave velocity. In some cases, the usual frequency gradient was reversed, with a plateau at a higher frequency than its proximal neighbor; thus fork dislocations were inverted, and the direction of propagation was reversed. Heptanol had no effect on the frequency or velocity of contractions but did reduce their amplitude. To understand intestinal motor patterns, the pacemaker network of the interstitial cells of Cajal is best evaluated as a system of coupled oscillators.

Left Atrial Appendage Resection Versus Preservation During the Surgical Ablation of Atrial Fibrillation

Left atrial appendage (LAA) resection during the Maze procedure may decrease thromboembolic risks, but its preservation may improve left atrial contractile function. This study compared the clinical effects of LAA resection and preservation after the Maze procedure. A retrospective review was made of 379 patients (mean age 53.3 ± 12.6 years, 244 females) who underwent the cryo-Maze procedure in conjunction with mitral surgery from 1999 to 2011. The LAA was resected in 187 patients (resection group) but preserved in 192 patients (preservation group). Outcomes were compared using a propensity score study design based on 20 baseline characteristics to obtain well-matched patient pairs. Propensity score matching yielded 119 pairs of patients in whom there were no significant differences in baseline profiles between the two groups. During a mean follow-up of 3.1 ± 2.8 years, there were 16 deaths, 6 cases of stroke, and 39 cases of atrial fibrillation recurrence. There were no significant differences in stroke-free survival (p = 0.88) and freedom from AF while off antiarrhythmic drugs (p = 0.46) between the two groups. On serial echocardiographic assessments, patients in the preservation group showed a higher transmitral A-wave velocity (peak atrial contraction wave velocity; p = 0.47, 0.020, and 0.001 at 3, 6, and 12 months, respectively) and lower E/A ratio (peak early filling wave [E-wave] velocity / A-wave velocity; p = 0.34, 0.065, and 0.001 at 3, 6, and 12 months, respectively) at each timepoint compared with the resection group. Preservation of the LAA during the Maze procedure resulted in similar clinical and rhythm outcomes, but LA contractile function superior to that of LAA resection.

Stiffening of Embryonic Myocarium during Development Parallels Myosin and Matrix Expression and Dynamically Matches Cell Function

Healthy heart function and structure, from the tissue to cellular scale, depends on establishment of proper tissue mechanics. On the cellular scale, late embryonic, neonatal and adult cardiomyocytes exhibit mechanosensitivity to ECM elasticity [1], such that culturing on substrates of physiological stiffness of ∼10-20 kPa optimizes function. However, the heart begins functioning long before this mature mechanical environment is established. Here we examine the effects of microenvironment mechanics on chick cardiomyocyte function during early development, embryonic day 2-4 (E2-E4). Micropipette aspiration measurements give an effective Young's modulus of ∼1-2 kPa at these earliest stages. Quantitative Mass Spectroscopy of embryonic myocardium identifies abundant structural proteins that most likely contribute to tissue mechanics. In particular, collagen I expression parallels the mechanical stiffening of the heart tissue. Treatment with collagenase or transglutaminase respectively softens or stiffens heart tissue in a dose dependent manner while maintaining functional cellular contractile machinery. Both stiffening and softening whole heart tubes reduces tissue strain during contraction, suggesting an optimum mechanics for myocardial contraction even at the earliest functional stages. Contraction wave velocity, however, changes proportionally to the stiffness of the tissue. E3-4 cardiomyocytes cultured on collagen-coated polyacrylamide gel substrates of different stiffnesses are best able to contract on substrates of ∼1.5 kPa, consistent with the physiological stiffness of the tissue from which they were derived. As in the whole heart, the cells were also less able to contract on much softer substrates of 300 Pa, or stiffer substrates of 10 kPa or more. This further points to optimizing mechanics for cardiomyocyte strain that matches the physiological stiffness of myocardium throughout development. Finally, effects environmental mechanics on nuclear proteins during development are being explored.[1] Majkut SF, Discher DE. (2012). BMMB. Doi: 10.1007/s10237-012-0413-8

A Mathematical Simulation of the Ureter: Effects of the Model Parameters on Ureteral Pressure/Flow Relations

Ureteral peristaltic mechanism facilitates urine transport from the kidney to the bladder. Numerical analysis of the peristaltic flow in the ureter aims to further our understanding of the reflux phenomenon and other ureteral abnormalities. Fluid-structure interaction (FSI) plays an important role in accuracy of this approach and the arbitrary Lagrangian-Eulerian (ALE) formulation is a strong method to analyze the coupled fluid-structure interaction between the compliant wall and the surrounding fluid. This formulation, however, was not used in previous studies of peristalsis in living organisms. In the present investigation, a numerical simulation is introduced and solved through ALE formulation to perform the ureteral flow and stress analysis. The incompressible Navier-Stokes equations are used as the governing equations for the fluid, and a linear elastic model is utilized for the compliant wall. The wall stimulation is modeled by nonlinear contact analysis using a rigid contact surface since an appropriate model for simulation of ureteral peristalsis needs to contain cell-to-cell wall stimulation. In contrast to previous studies, the wall displacements are not predetermined in the presented model of this finite-length compliant tube, neither the peristalsis needs to be periodic. Moreover, the temporal changes of ureteral wall intraluminal shear stress during peristalsis are included in our study. Iterative computing of two-way coupling is used to solve the governing equations. Two phases of nonperistaltic and peristaltic transport of urine in the ureter are discussed. Results are obtained following an analysis of the effects of the ureteral wall compliance, the pressure difference between the ureteral inlet and outlet, the maximum height of the contraction wave, the contraction wave velocity, and the number of contraction waves on the ureteral outlet flow. The results indicate that the proximal part of the ureter is prone to a higher shear stress during peristalsis compared with its middle and distal parts. It is also shown that the peristalsis is more efficient as the maximum height of the contraction wave increases. Finally, it is concluded that improper function of ureteropelvic junction results in the passage of part of urine back flow even in the case of slow start-up of the peristaltic contraction wave.

A New Method for Detection and Quantification of Heartbeat Parameters in Drosophila, Zebrafish, and Embryonic Mouse Hearts

The genetic basis of heart development is remarkably conserved from Drosophila to mammals, and insights from flies have greatly informed our understanding of vertebrate heart development. Recent evidence suggests that many aspects of heart function are also conserved and the genes involved in heart development also play roles in adult heart function. We have developed a Drosophila heart preparation and movement analysis algorithm that allows quantification of functional parameters. Our methodology combines high-speed optical recording of beating hearts with a robust, semi-automated analysis to accurately detect and quantify, on a beat-to-beat basis, not only heart rate but also diastolic and systolic intervals, systolic and diastolic diameters, percent fractional shortening, contraction wave velocity, and cardiac arrhythmicity. Here, we present a detailed analysis of hearts from adult Drosophila, 2-3-day-old zebrafish larva, and 8-day-old mouse embryos, indicating that our methodology is potentially applicable to an array of biological models. We detect progressive age-related changes in fly hearts as well as subtle but distinct cardiac deficits in Tbx5 heterozygote mutant zebrafish. Our methodology for quantifying cardiac function in these genetically tractable model systems should provide valuable insights into the genetics of heart function.

Abstract 2822: Imaging of the Propagation of the Contraction Wave Using RF-Based Speckle Tracking In Vivo

OBJECTIVE : Using a combination of high-frequency ultrasonography, ECG gating, and RF-based motion estimation, our laboratory has developed a novel technique for the noninvasive mapping of contraction waves in the intact murine left ventricle. In this study, we sought to measure the velocity and direction of contraction waves in the murine heart during native conduction and pacing. METHODS : Twelve wild-type mice were anesthetized with IP pentobarbital, and an octapolar pacing catheter introduced into the right ventricle (RV) through the external jugular vein. In vivo ultrasound RF frames (30 MHz) were acquired at 8000 fps (Vevo 770, Visualsonics, Inc.), using ECG gating. Axial frame-to-frame motion were estimated using a speckle tracking method. Images were obtained in the parasternal long axis view under three conditions; sinus rhythm (SR), right atrial (RA) pacing, and RV pacing. Contraction was analyzed using ciné-loop images. RESULTS : Distinct contraction patterns were noted during isovolumic contraction (IC) ejection under all conditions. In SR, during IC, convergent motion of the septal wall (SW) and posterior wall (PW) began during the latter half of the QRS at the apex and spread basally, causing divergent movement at the base. At the onset of ejection, medial contraction spread to the base. Similar results were obtained with RA pacing. During RV pacing, the IC phase began with convergent motion of the basal SW and PW that spread apically, causing divergent motion of the apical SW and PW. During ejection, convergent motion of the apical SW and PW developed which spread to the basal SW and PW. This difference between SR/RA pacing and RV pacing was found in all mice (n=12). We found a significantly slower contraction wave velocity during RV pacing (0.5213 +/- 0.3125 m/s) than during SR/RA pacing (0.8496 ± 0.2214 and 0.8379 ± 0.1967 m/s, respectively) (p<0.01), in line with previously reported results. CONCLUSION : This study demonstrates the ability of this modality to noninvasively map the velocity and direction of contraction waves. Using this technique, we demonstrate the difference in motion patterns between native conduction and ventricular pacing. This technique has potential applications in the noninvasive assessment of ventricular dyssynchrony.

Right and left ventricular adaptation to hypoxia: a tissue Doppler imaging study

Hypoxia has been reported to alter left ventricular (LV) diastolic function, but associated changes in right ventricular (RV) systolic and diastolic function remain incompletely documented. We used echocardiography and tissue Doppler imaging to investigate the effects on RV and LV function of 90 min of hypoxic breathing (fraction of inspired O(2) of 0.12) compared with those of dobutamine to reproduce the same heart rate effects without change in pulmonary vascular tone in 25 healthy volunteers. Hypoxia and dobutamine increased cardiac output and tricuspid regurgitation velocity. Hypoxia and dobutamine increased LV ejection fraction, isovolumic contraction wave velocity (ICV), acceleration (ICA), and systolic ejection wave velocity (S) at the mitral annulus, indicating increased LV systolic function. Dobutamine had similar effects on RV indexes of systolic function. Hypoxia did not change RV area shortening fraction, tricuspid annular plane systolic excursion, ICV, ICA, and S at the tricuspid annulus. Regional longitudinal wall motion analysis revealed that S, systolic strain, and strain rate were not affected by hypoxia and increased by dobutamine on the RV free wall and interventricular septum but increased by both dobutamine and hypoxia on the LV lateral wall. Hypoxia increased the isovolumic relaxation time related to RR interval (IRT/RR) at both annuli, delayed the onset of the E wave at the tricuspid annulus, and decreased the mitral and tricuspid inflow and annuli E/A ratio. We conclude that hypoxia in normal subjects is associated with altered diastolic function of both ventricles, improved LV systolic function, and preserved RV systolic function.

Non-Invasive Detection of Acute Allograft Rejection in Children by Tissue Doppler Imaging: Myocardial Velocities and Myocardial Acceleration During Isovolumic Contraction

In adults, an acute decrease of regional myocardial velocities is a sensitive marker of rejection. In children, velocities are more variable. A new marker, myocardial acceleration during isovolumic contraction (IVA), appears to be less age-dependent than myocardial velocities. This study therefore compared tissue Doppler (TDI)-derived velocities and IVA as potential rejection markers for children. TDI was performed in 15 pediatric heart transplant recipients (age 8.0 +/- 3.6 years) during acute rejection and at baseline without rejection, 50 additional transplant children without rejection (7.8 +/- 5.9 years) and 30 age-matched healthy children (7.5 +/- 5.2 years). Color Doppler cine-loops of 3 cardiac cycles were stored as echocardiographic raw data. Using off-line post-processing, systolic (S) and diastolic (E) myocardial velocities and IVA were measured in 5 basal left ventricular segments. IVA is the peak isovolumic contraction wave velocity divided by acceleration time. Without rejection, transplant children had significantly lower diastolic velocities (basal lateral E 10.4 +/- 2.9 vs 11.9 +/- 2.6 cm/s; p < 0.001) and systolic velocities (S 5.6 +/- 1.4 vs 7.1 +/- 2.0 cm/s; p < 0.001) than normal age-matched controls, but IVA was similar (1.2 +/- 1.4 vs 1.3 +/- 0.5 m/s2). During rejection, all markers decreased significantly compared with age-matched normal control, the non-rejecting transplant group and individual baseline values. Regional myocardial velocities change significantly during acute allograft rejection in children. However, many children already have wall motion abnormalities at baseline, so results are often difficult to interpret. In contrast, isovolumic acceleration was normal without rejection and selectively decreased during the event. IVA is a promising non-invasive rejection marker for pediatric patients.