Alteration of the native mitral valve (MV) shape has been hypothesized to have a profound effect on the local tissue stress distribution, and is potentially linked to limitations in repair durability. The present study was undertaken to elucidate the relation between MV annular shape and central mitral valve anterior leaflet (MVAL) strain history, using flat annuloplasty in an ovine model. In addition, we report for the first time the presence of residual in-vivo leaflet strains. In-vivo leaflet deformations were measured using sonocrystal transducers sutured to the MVAL (n=10), with the 3D positions acquired over the full cardiac cycle. In six animals a flat ring was sutured to the annulus and the transducer positions recorded, while in the remaining four the MV was excised from the exsanguinated heart and the stress-free transducer positions obtained. In the central region of the MVAL the peak stretch values, referenced to the minimum left ventricular pressure (LVP), were 1.10 ± 0.01 and 1.31 ± 0.03 (mean ± standard error) in the circumferential and radial directions, respectively. Following flat ring annuloplasty, the central MVAL contracted 28% circumferentially and elongated 16% radially at minimum LVP, and the circumferential direction was under a negative strain state during the entire cardiac cycle. After valve excision from the exsanguinated heart, the MVAL contracted significantly (18% and 30% in the circumferential and radial directions, respectively), indicating the presence of substantial in-vivo residual strains. While the physiological function of the residual strains (and their associated stresses) are at present unknown, accounting for their presence is clearly necessary for accurate computational simulations of MV function. Moreover, we demonstrated that changes in annular geometry dramatically alter valvular functional strains in-vivo. As levels of homeostatic strains are related to tissue remodeling and homeostasis, our results suggest that surgically-introduced alterations in MV shape could lead to the long term MV mechanobiological and microstructural alterations that could ultimately affect MV repair durability.

Background Studies of the biomechanical response of the left ventricle (LV) to myocardial infarction (MI) have identified infarct expansion as an important phenomenon that both initiates and sustains adverse LV remodeling. We tested the hypothesis that infarct modification via material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling. Methods Twenty-one sheep had anteroapical infarction and were randomized to either injection of 2.6ml of saline or 2.6ml of a tissue filler material into the infarct within 3 hours of coronary occlusion. Animals were followed for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Post-mortem morphometric measurements were performed on the excised heart to quantify infarct thickness; regional blood flow was assessed with colored microspheres. Infarct material properties were directly measured using biaxial tensile testing. Results Treatment animals had less infarct expansion and reduced LV dilatation 8 weeks after MI (LV systolic volumes 60.8±4.3ml vs. 80.3±6.9ml, p<0.05). Ejection fraction was greater in the treatment animals (31.0±2.6% vs. 27.6±1.3%, p<0.05). The treatment group had thicker infarcts (5.5±0.2mm vs. 2.2±0.3mm, p<0.05) and greater infarct blood flow than control groups (0.22±0.04ml/min/g vs. 0.11±0.03ml/min/g, p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts. Conclusion Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection resulting in the amelioration of both infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm.

While the role of collagen and elastin fibrous components in heart valve valvular biomechanics has been extensively investigated [see Sacks et al. 2009 J. Biomech. 42, 1804-24], the biomechanical role of the glycosaminoglycan (GAG) gelatinous-like material phase remains unclear. In the present study, we investigated the biomechanical role of GAGs in porcine aortic valve (AV) leaflets under tension utilizing enzymatic removal. Tissue specimens were removed from the belly region of porcine AVs and subsequently treated with either an enzyme solution for GAG removal, or a control (buffer with no enzyme) solution. A dual stress level test methodology was used to determine the effects at low and high (physiological) stress levels). In addition, planar biaxial tests were conducted both on-axis (i.e. aligned to the circumferential and radial axes) and at 45° off-axis to induce maximum shear, to explore the effects of augmented fiber rotations on the fiber-fiber interactions. Changes in hysteresis were used as the primary metric of GAG functional assessment. A simulation of the low force experimental setup was also conducted to clarify the internal stress system and provide viscoelastic model parameters fo this loading range. Results indicated that under planar tension the removal of GAGs had no measureable affect extensional mechanical properties (either on- or 45° off-axis) including peak stretch, hysteresis, or creep. Interestingly, in the low force range, hysteresis was markedly reduced from 35.96 ± 2.65% in control group to 25.00 ± 1.64% (p < 0.001) as a result of GAG removal. Collectively, these results suggest that GAGs do not play a direct role in modulating the time-dependent tensile properties of valvular tissues. Rather, they appear to be strongly connected with fiber-fiber and fiber-matrix interactions at low forces levels. Thus, we speculate that GAGs may be important in providing a damping mechanism to reduce leaflet flutter when the leaflet is not under high tensile stress.

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