BACKGROUND Transection of the secondary chordae on the anterior leaflet of the mitral valve to relieve leaflet tethering and reduce regurgitation is an experimentally proven procedure to correct functional mitral regurgitation. In this study, we sought to investigate if transecting the secondary chordae has an impact on the marginal chordal force on the same leaflet. METHODS Adult porcine mitral valves (N =8) were studied in a pulsatile heart simulator, in which the papillary muscle positions can be precisely positioned. The anterior marginal chordae were instrumented with miniature transducers to measure the chordal forces. Each valve was studied under baseline conditions, three different tethering conditions [apical, apical-lateral, apical-lateral-posterior], and following chordal cutting in the three tethering conditions. The temporal changes, the peak and average marginal chordal forces under each condition are reported. RESULTS Apical tethering increased marginal chordal force by an average 96% but remained unchanged after chordal cutting. With apical-lateral tethering, marginal chordal force increased by 210% from baseline, and further increased to 350% of baseline after chordal cutting. After apical-lateral-posterior tethering, the marginal chordal force increased to 335% of baseline before transection and by 548% after the transection. CONCLUSIONS Increase in marginal chordal force after secondary chordal cutting depends on the location of the papillary muscles and the extent of leaflet tethering. While, chordal cutting may not alter the valve mechanics under minimal leaflet tethering, it significantly impacts the mechanics when the leaflet tethering is more pronounced, which is typically seen in patients with functional mitral regurgitation.

BACKGROUND Surgical reconstruction of a flail posterior leaflet is a routine mitral valve repair, the techniques for which have evolved from leaflet resection to leaflet preservation. Artificial ePTFE neochordae are frequently used to stabilize the flail leaflet, and seldom translocation of the native secondary chordae of the valve to the leaflet free edge is used. In this study, we sought to investigate the efficacy of the two techniques to correct posterior leaflet prolapse and reduce mitral regurgitation, and quantify the acute post-repair leaflet kinematics. METHODS Adult porcine mitral valves (N =7) were studied in a pulsatile left heart experimental model in which isolated P2 flail was mimicked by marginal chordal transection. Baseline conditions were established in each valve under normal conditions (control), and followed by induction of isolated P2 flail by transecting the two marginal chordae on the posterior leaflet free edge (disease). The flail posterior leaflet was reconstructed using artificial neochordae (repair 1) and then native chordal translocation (repair 2). Reduction in leaflet flail, changes in mitral regurgitation fraction, leaflet coaptation length, and posterior leaflet mobility were measured using B-mode echocardiography or color doppler. RESULTS At baseline, all the valves were competent with no mitral regurgitation. After transection of the marginal chordae on the posterior leaflet, isolated P2 flail was evident with 13.7±13% regurgitation. Reconstruction with artificial neochordae eliminated leaflet flail and reduced mitral regurgitation to 3.2± 2.8%, and with chordal translocation leaflet flail was corrected and mitral regurgitation was measured at 2.3±2.6%. Using either repair techniques, leaflet coaptation and mobility of the repaired leaflets were adequate and comparable to the baseline measurements. CONCLUSIONS Comparable reduction leaflet flail and regurgitation, and restoration of physiological leaflet coaptation with the two techniques indicates that under acute conditions, use of artificial neochordae or native chordal translocations have similar benefits.

The importance of tissue remodelling is widely accepted, but the mechanism by which the remodelling process occurs remains poorly understood. At the tissue scale, the concept of tensional homeostasis, in which there exists a target stress for a cell and remodelling functions to move the cell stress towards that target, is an important foundation for much theoretical work. We present here a theoretical model of a cell in parallel with a network to study what factors of the remodelling process help the cell move towards mechanical stability. The cell-network system was deformed and kept at constant stress. Remodelling was modelled by simulating strain-dependent degradation of collagen fibres and four different cases of collagen addition. The model did not lead to complete tensional homeostasis in the range of conditions studied, but it showed how different expressions for deposition and removal of collagen in a fibre network can interact to modulate the cell's ability to shield itself from an imposed stress by remodelling the surroundings. This study also showed how delicate the balance between deposition and removal rates is and how sensitive the remodelling process is to small changes in the remodelling rules.

The minor type IV collagen chain, which is a significant component of the glomerular basement membrane in healthy individuals, is known to assemble into large structures (supercoils) that may contribute to the mechanical stability of the collagen network and the glomerular basement membrane as a whole. The absence of the minor chain, as in Alport syndrome, leads to glomerular capillary demise and eventually to kidney failure. An important consideration in this problem is that the glomerular capillary wall must be strong enough to withstand the filtration pressure and porous enough to permit filtration at reasonable pressures. In this work, we propose a coupled feedback loop driven by filtration demand and tensional homeostasis of the podocytes forming the outer portion the glomerular capillary wall. Briefly, the deposition of new collagen increases the stiffness of basement membrane, helping to stress shield the podocytes, but the new collagen also decreases the permeability of the basement membrane, requiring an increase in capillary transmural pressure drop to maintain filtration; the resulting increased pressure outweighs the increased glomerular basement membrane stiffness and puts a net greater stress demand on the podocytes. This idea is explored by developing a multiscale simulation of the capillary wall, in which a macroscopic (μm-scale) continuum model is connected to a set of microscopic (nm-scale) fiber network models representing the collagen network and the podocyte cytoskeleton. The model considers two cases: healthy remodeling, in which the presence of the minor chain allows the collagen volume fraction to be increased by thickening fibers, and Alport syndrome remodeling, in which the absence of the minor chain allows collagen volume fraction to be increased only by adding new fibers to the network. The permeability of the network is calculated based on previous models of flow through a fiber network, and it is updated for different fiber radii and volume fractions. The analysis shows that the minor chain allows a homeostatic balance to be achieved in terms of both filtration and cell tension. Absent the minor chain, there is a fundamental change in the relation between the two effects, and the system becomes unstable. This result suggests that mechanobiological or mechanoregulatory therapies may be possible for Alport syndrome and other minor-chain collagen diseases of the kidney.