Objective To describe effects of non‐ablative erbium‐doped:yttrium‐aluminium‐garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. Design Animal experimental, randomised, sham and estrogen‐treatment controlled study with blinding for primary outcome. Setting KU Leuven, Belgium. Sample Twenty‐four ewes. Methods Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1‐month interval; three sham manipulations with a 1‐month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. Main outcome measures Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. Results Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser‐treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen‐substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. Conclusions Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. Tweetable abstract Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

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Secondary mitral regurgitation occurs when a left ventricular problem causes leaking of the mitral valve. The altered left ventricular geometry changes the orientation of the subvalvular apparatus, thereby affecting the mechanical stress on the mitral valve. This in turn leads to active remodeling of the mitral valve, in order to compensate for the ventricular remodeling. In this study, a biomechanical analysis was performed on eight human mitral valves with secondary mitral regurgitation and ten healthy human mitral valves to better understand this pathophysiology and its effect on the mechanical properties of these tissues. Samples were obtained from the anterior and posterior leaflet and used for planar biaxial mechanical experiments. Uniaxial experiments were performed on four groups of mitral valve chords: anterior basal, anterior marginal, posterior basal and posterior marginal chords. The mechanical response of the mitral valve leaflets was fitted to the May-Newman and Yin constitutive model, whereas the material parameters of the third order Ogden model were determined for the chord samples. Next, stiffnesses calculated at low and high stress levels were statistically analyzed. Leaflet samples with secondary mitral regurgitation showed a small thickness increase and a change in anisotropy index compared to healthy control valves. Diseased leaflets were more compliant circumferentially and stiffer radially, resulting in anisotropic samples with the radial direction being stiffest. In addition, chord samples were slightly thicker and less stiff at high stress in secondary mitral regurgitation, when grouped per leaflet type and insertion region. These results confirm mechanical alterations due to the pathophysiological valvular changes caused by left ventricular remodeling. It is important that these changes in mechanical behavior are incorporated into computational models of the mitral valve.

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Collagen fibers and their orientation greatly influence an artery's mechanical characteristics, determining its transversely isotropic behavior. It is generally assumed that these fibers are deposited along a preferred direction to maximize the load bearing capacity of the vessel wall. This implies a large spatial variation in collagen orientation which can be reconstructed in numerical models using so-called reorientation algorithms. Until now, these algorithms have used the classical continuum mechanics modeling framework which requires knowledge of tissue-level parameters and the artery's stressfree reference state, which is inaccessible in a clinical context. We present an algorithm to compute the preferred fiber distribution compatible with the constrained mixture theory, which orients two collagen fiber families according to the loading experienced by the isotropic non-collagenous extracellular matrix, without requiring prior knowledge of the stress-free state. Because consensus is lacking whether stress or stretch is the determining factor behind the preferred fiber distribution, we implemented both approaches and compared the results with experimental microstructural data of an abdominal aorta. The stress-based algorithm was able to describe several experimentally observed transitions of the fiber distribution across the intima, media and adventitia.