Papillary Muscles

BackgroundSphingolipid deposition in Fabry disease causes left ventricular (LV) hypertrophy, of which the accurate assessment is essential. Cardiovascular magnetic resonance (CMR) has been proposed as the gold standard. However, there is debate in the literature as to whether papillary muscles and trabeculations (P&T) should be included in LV mass (LVM).Methods/resultsWe examined the accuracy of 2 CMR methods of assessing LVM and LV volumes, including (M inc P&T) or excluding (M ex P&T) P&T, in a cohort of Fabry disease subjects (n = 20) compared to a matched control group (n = 20). Significant differences between the two measurement methods were observed for LV end-diastolic volume, LV end-systolic volume, LVM, and LV ejection fraction (LVEF) in both groups. These differences were significantly greater in the Fabry group compared to controls, except for LVEF. P&T contributed to a greater percentage of LVM in Fabry subjects than controls (20 ± 1% vs 13 ± 2%, p = 0.01). In the control group, both volume-derived methods (M inc P&T or MexP&T) provided accurate SV measurements compared with the internal reference of velocity-encoded aortic flow. In the Fabry group, inclusion of P&T (M inc P&T) resulted in good concordance with phase contrast flow imaging (difference between flow and volume techniques: 1 ± 3 ml, p = 0.7).ConclusionThe volumetric contribution of P&T in Fabry disease is markedly increased relative to healthy controls. Failure to account for this results in significant underestimation of LVM and results in misclassification of a proportion of subjects.

ObjectivesFunctional mitral regurgitation (FMR) is a significant complication of left ventricle (LV) dysfunction associated with poor prognosis and commonly treated by undersized ring annuloplasty. This study aimed to quantitatively simulate the treatment outcomes and mitral valve (MV) biomechanics following ring annulopalsty and papillary muscle relocation (PMR) procedures for a FMR patient.MethodsWe utilized a validated finite element model of the left heart for a patient with severe FMR and LV dilation from our previous study and simulated virtual ring annuloplasty procedures with various sizes of Edwards Classic and GeoForm annuloplasty rings. The model included detailed geometries of the left ventricle, mitral valve, and chordae tendineae, and incorporated age- and gender- matched nonlinear, anisotropic hyperelastic tissue material properties, and simulated chordal tethering at diastole due to LV dilation.ResultsRing annuloplasty with either the Classic or GeoForm ring improved leaflet coaptation and increased the total leaflet closing force while increased posterior mitral leaflet (PML) stresses and strains. Classic rings resulted in larger coaptation forces and areas compared to GeoForm rings. The PMR procedure further improved the leaflet coaptation, decreased the PML stress and strain for both ring shapes and all sizes in this patient model.ConclusionsThis study demonstrated that a rigorously developed patient-specific computational model can provide useful insights into annuloplasty repair techniques for the treatment of FMR patients and could potentially serve as a tool to assist in pre-operative planning for MV repair surgical or interventional procedures.

Multiphoton microscopy is a powerful, non-invasive technique to image biological specimens. One current limitation of multiphoton microscopy is resolution as many of the biological molecules and structures investigated by research groups are similar in size or smaller than the diffraction limit. To date, the combination of multiphoton and super-resolution imaging has proved technically challenging for biology focused laboratories to implement. Here we validate that the commercial super-resolution Airyscan detector from ZEISS, which is based on image scanning microscopy, can be integrated under warranty with a pulsed multi-photon laser to enable multiphoton microscopy with super-resolution. We demonstrate its biological application in two different imaging modalities, second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), to measure the fibre thicknesses of collagen and elastin molecules surpassing the diffraction limit by a factor of 1.7±0.3x and 1.4±0.3x respectively, in human heart and lung tissues, and 3-dimensional in vitro models. We show that enhanced resolution and signal-to-noise of SHG using the Airyscan compared to traditional GaAs detectors allows for automated and precise measurement of collagen fibres using texture analysis in biological tissues.

In this study, we aimed to investigate the effects of cumulative doses of Zn2+ (by exposing samples to 1 µM, 10 µM, and 100 µM ZnCl2) on myocardial papillary muscle contractions isolated from rat hearts in vitro and the roles of the zinc finger protein ZEB1 in this effect. In these preparations, 100 µM ZnCl2 application in different protocols caused a decrease in contraction force and an increase in contraction time in both frequency-dependent parameters and pre-expected stimuli when compared to the control group. Our study data show that Ca2+ homeostasis is closely related to increasing Zn2+ doses (especially at 100 µM ZnCl2 dose). Secondly, the levels of ZEB1, a zinc finger protein, were also significantly lower in the 100 µM ZnCl2 group compared to the other groups, which seems to be related to the increase in Ca2+ that triggers ROS production at high doses of Zn2+. The data of our study, which we conducted to understand the Zn2+ concentrations in the heart and to reveal new mechanisms that play a role in the regulation of Ca2+ dynamics in heart tissue and is the first research in the literature on this subject, show that in vitro zinc application may have a dose-dependent effect on myocardial papillary muscle contractions.