Regional stiffening of the mitral valve anterior leaflet in the beating ovine heart

Left atrial muscle extends into the proximal third of the mitral valve (MV) anterior leaflet and transient tensing of this muscle has been proposed as a mechanism aiding valve closure. If such tensing occurs, regional stiffness in the proximal anterior mitral leaflet will be greater during isovolumic contraction (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference will be selectively abolished by β-receptor blockade. We tested this hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and after administration of esmolol (ESML). Heterogeneous finite element models of each anterior leaflet were developed using marker coordinates over matched pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were simulated using measured left ventricular and atrial pressures and a response function was computed as the difference between simulated and measured displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and EDGE leaflet regions were iteratively varied until the response function reached a minimum. The stiffness values at this minimum were interpreted as the in vivo regional material properties of the anterior leaflet. For all regions and all CTRL beats IVC stiffness was 40–58% greater than IVR stiffness. ESML reduced ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly implicate transient tensing of leaflet atrial muscle during IVC as the basis of the ANNULAR IVC–IVR stiffness difference.     

Vagal nerve stimulation reduces anterior mitral valve leaflet stiffness in the beating ovine heart

Aim: The functional significance of the autonomic nerves in the anterior mitral valve leaflet (AML) is unknown. We tested the hypothesis that remote stimulation of the vagus nerve (VNS) reduces AML stiffness in the beating heart. Methods: Forty-eight radiopaque-markers were implanted into eleven ovine hearts to delineate left ventricular and mitral anatomy, including an AML array. The anesthetized animals were then taken to the catheterization laboratory and 4-D marker coordinates obtained from biplane videofluoroscopy before and after VNS. Circumferential (E_circ) and radial (E_rad) stiffness values for three separate AML regions, Annulus, Belly and Edge, were obtained from inverse finite element analysis of AML displacements in response to trans-leaflet pressure changes during isovolumic contraction (IVC) and isovolumic relaxation (IVR). Results: VNS reduced heart rate: 94±9 vs. 82±10 min^?1, (mean±SD, p<0.001). Circumferential AML stiffness was significantly reduced in all three regions during IVC and IVR (all p<0.05). Radial AML stiffness was reduced from control in the annular and belly regions at both IVC and IVR (P<0.05), while the reduction did not reach significance at the AML edge. Conclusion: These observations suggest that one potential functional role for the parasympathetic nerves in the AML is to alter leaflet stiffness. Neural control of the contractile tissue in the AML could be part of a central control system capable of altering valve stiffness to adapt to changing hemodynamic demands.     

Tricuspid valve leaflet strains in the beating ovine heart

Biomechanics and Modeling in Mechanobiology - The tricuspid leaflets coapt during systole to facilitate proper valve function and, thus, ensure efficient transport of deoxygenated blood to the...     

Stress–strain behavior of mitral valve leaflets in the beating ovine heart

Excised anterior mitral leaflets exhibit anisotropic, non-linear material behavior with pre-transitional stiffness ranging from 0.06 to 0.09 N/mm² and post-transitional stiffness from 2 to 9 N/mm². We used inverse finite element (FE) analysis to test, for the first time, whether the anterior mitral leaflet (AML), in vivo, exhibits similar non-linear behavior during isovolumic relaxation (IVR). Miniature radiopaque markers were sewn to the mitral annulus, AML, and papillary muscles in 8 sheep. Four-dimensional marker coordinates were obtained using biplane videofluoroscopic imaging during three consecutive cardiac cycles. A FE model of the AML was developed using marker coordinates at the end of isovolumic relaxation (when pressure difference across the valve is approximately zero), as the reference state. AML displacements were simulated during IVR using measured left ventricular and atrial pressures. AML elastic moduli in the radial and circumferential directions were obtained for each heartbeat by inverse FEA, minimizing the difference between simulated and measured displacements. Stress–strain curves for each beat were obtained from the FE model at incrementally increasing transmitral pressure intervals during IVR. Linear regression of 24 individual stress–strain curves (8 hearts, 3 beats each) yielded a mean (±SD) linear correlation coefficient (r²) of 0.994±0.003 for the circumferential direction and 0.995±0.003 for the radial direction. Thus, unlike isolated leaflets, the AML, in vivo, operates linearly over a physiologic range of pressures in the closed mitral valve.     

Visual complications of mitral leaflet prolapse.

Four young women and six older men with mitral leaflet prolapse presented with visual disturbances consistent with embolism in the ophthalmic or posterior cerebral circulation. Cardiac arrhythmias were common, but these are rarely associated with focal ischaemia. The evidence that mitral leaflet prolapse caused the embolism in these patients is suggestive but not conclusive. Further studies are needed. All patients with acute cerebral or ocular ischaemia should undergo through cardiovascular assessment, which should include routine echocardiography.     

Stability analysis of one-dimensional dynamical systems applied to an isolated beating heart

In this paper we propose a new model of an isolated beating heart. The model is described by a one-dimensional non-linear discrete dynamical system which depends on several parameters. Applying stability analysis we investigate the dynamic properties of the non-linear system. We find those domains in the parameter space in which the equilibrium point of the system (the fixed point) and the periodic orbits are attractors and in which they are unstable. These domains correspond to a normal and abnormal beating heart, i.e. when the end diastolic volumes are stable time invariant and time variant, respectively. On transition between these domains there is a bifurcation which gives rise to a pair of attracting points of period 2. This case corresponds to the simplest type of period doubling behavior of an abnormal beating heart, called mechanical alternans. Our results provide qualitative and quantitative predictions which can be used for comprehensive experimental design.     

Ablation of mitral annular and leaflet muscle: effects on annular and leaflet dynamics

Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferential phenol ablation of the MA and anterior mitral leaflet (AML) muscle. Radiopaque markers were sutured to the left ventricle, MA, and both mitral leaflets in 18 sheep. In 10 sheep, phenol was applied circumferentially to the atrial surface of the mitral annulus and the hinge region of the AML, whereas 8 sheep served as controls. Animals were studied with biplane video fluoroscopy for computation of 3-D mitral annular area (MAA) and leaflet shape. MAA contraction (MAACont) was determined from maximum to minimum value. Presystolic MAA (PS-MAACont) reduction was calculated as the percentage of total reduction occurring before end diastole. Phenol ablation decreased PS-MAACont (72 +/- 6 vs. 47 +/- 31%, P = 0.04) and delayed valve closure (31 +/- 11 vs. 57 +/- 25 ms, P = 0.017). In control, the AML had a compound sigmoid shape; after phenol, this shape was entirely concave to the atrium during valve closure. These data indicate that myocardial fibers on the atrial side of the valve influence the 3-D dynamic geometry and shape of the MA and AML.     

In vivo dynamic strains of the ovine anterior mitral valve leaflet

Understanding the mechanics of the mitral valve is crucial in terms of designing and evaluating medical devices and techniques for mitral valve repair. In the current study we characterize the in vivo strains of the anterior mitral valve leaflet. On cardiopulmonary bypass, we sew miniature markers onto the leaflets of 57 sheep. During the cardiac cycle, the coordinates of these markers are recorded via biplane fluoroscopy. From the resulting four-dimensional data sets, we calculate areal, maximum principal, circumferential, and radial leaflet strains and display their profiles on the averaged leaflet geometry. Average peak areal strains are 13.8±6.3%, maximum principal strains are 13.0±4.7%, circumferential strains are 5.0±2.7%, and radial strains are 7.8±4.3%. Maximum principal strains are largest in the belly region, where they are aligned with the circumferential direction during diastole switching into the radial direction during systole. Circumferential strains are concentrated at the distal portion of the belly region close to the free edge of the leaflet, while radial strains are highest in the center of the leaflet, stretching from the posterior to the anterior commissure. In summary, leaflet strains display significant temporal, regional, and directional variations with largest values inside the belly region and toward the free edge. Characterizing strain distribution profiles might be of particular clinical significance when optimizing mitral valve repair techniques in terms of forces on suture lines and on medical devices.     

In vitro dynamic strain behavior of the mitral valve posterior leaflet

Knowledge of mitral valve (MV) mechanics is essential for the understanding of normal MV function, and the design and evaluation of new surgical repair procedures. In the present study, we extended our investigation of MV dynamic strain behavior to quantify the dynamic strain on the central region of the posterior leaflet. Native porcine MVs were mounted in an in-vitro physiologic flow loop. The papillary muscle (PM) positions were set to the normal, taut, and slack states to simulate physiological and pathological PM positions. Leaflet deformation was measured by tracking the displacements of 16 small markers placed in the central region of the posterior leaflet. Local leaflet tissue strain and strain rates were calculated from the measured displacements under dynamic loading conditions. A total of 18 mitral valves were studied. Our findings indicated the following: (1) There was a rapid rise in posterior leaflet strain during valve closure followed by a plateau where no additional strain (i.e., no creep) occurred. (2) The strain field was highly anisotropic with larger stretches and stretch rates in the radial direction. There were negligible stretches, or even compression (stretch < 1) in the circumferential direction at the beginning of valve closure. (3) The areal strain curves were similar to the stretches in the trends. The posterior leaflet showed no significant differences in either peak stretches or stretch rates during valve closure between the normal, taut, and slack PM positions. (4) As compared with the anterior leaflet, the posterior leaflet demonstrated overall lower stretch rates in the normal PM position. However, the slack and taut PM positions did not demonstrate the significant difference in the stretch rates and areal strain rates between the posterior leaflet and the anterior leaflet. The MV posterior leaflet exhibited pronounced mechanically anisotropic behavior Loading rates of the MV posterior leaflet were very high. The PM positions influenced neither peak stretch nor stretch rates in the central area of the posterior leaflet. The stretch rates and areal strain rates were significantly lower in the posterior leaflet than those measured in the anterior leaflet in the normal PM position. However, the slack and taut PM positions did not demonstrate the significant differences between the posterior leaflet and the anterior leaflet. We conclude that PM positions may influence the posterior strain in a different way as compared to the anterior leaflet.     

Mechanism of incomplete mitral leaflet coaptation--interaction of chordal restraint and changes in mitral leaflet coaptation geometry. Insight from in vitro validation of the premise of force equilibrium

Clinically observed incomplete mitral leaflet coaptation was reproduced in vitro by altering the balance of the chordal tethering and chordal coapting force components. Mitral leaflet coaptation geometry was distorted by changes of the spatial relations between the papillary muscles and the mitral valve as well as hemodynamics. Mitral leaflet malalignment was accentuated by a redistribution of the chordal tethering and coapting force components. For the overall assessment of systolic mitral leaflet configuration in functional mitral regurgitation it is important to consider the interaction between chordal restraint and an altered mitral leaflet coaptation geometry.     

Interlayer micromechanics of the aortic heart valve leaflet

While the mechanical behaviors of the fibrosa and ventricularis layers of the aortic valve (AV) leaflet are understood, little information exists on their mechanical interactions mediated by the GAG-rich central spongiosa layer. Parametric simulations of the interlayer interactions of the AV leaflets in flexure utilized a tri-layered finite element (FE) model of circumferentially oriented tissue sections to investigate inter-layer sliding hypothesized to occur. Simulation results indicated that the leaflet tissue functions as a tightly bonded structure when the spongiosa effective modulus was at least 25 % that of the fibrosa and ventricularis layers. Novel studies that directly measured transmural strain in flexure of AV leaflet tissue specimens validated these findings. Interestingly, a smooth transmural strain distribution indicated that the layers of the leaflet indeed act as a bonded unit, consistent with our previous observations (Stella and Sacks in J Biomech Eng 129:757–766, 2007) of a large number of transverse collagen fibers interconnecting the fibrosa and ventricularis layers. Additionally, when the tri-layered FE model was refined to match the transmural deformations, a layer-specific bimodular material model (resulting in four total moduli) accurately matched the transmural strain and moment-curvature relations simultaneously. Collectively, these results provide evidence, contrary to previous assumptions, that the valve layers function as a bonded structure in the low-strain flexure deformation mode. Most likely, this results directly from the transverse collagen fibers that bind the layers together to disable physical sliding and maintain layer residual stresses. Further, the spongiosa may function as a general dampening layer while the AV leaflets deforms as a homogenous structure despite its heterogeneous architecture.     

Dynamics of flow in a mechanical heart valve: the role of leaflet inertia and leaflet compliance

In this work, we examine the dynamics of fluid flow in a mechanical heart valve when the solid inertia and leaflet compliance are important. The fluid is incompressible and Newtonian, and the leaflet is an incompressible neo-Hookean material. In the case of an inertialess leaflet, we find that the maximum valve opening angle and the time that the valve remains closed increase as the shear modulus of the leaflet decreases. More importantly, the regurgitant volume decreases with decreasing shear modulus. When we examined the forces exerted on the leaflet, we found that the downward motion of the leaflet is initiated by a vertical force exerted on its right side and, later on, by a vertical force exerted on the top side of the leaflet. In the case of solid inertia, we find that the maximum valve opening angle and the regurgitant volume are larger than in the case of an inertialess leaflet. These results highlight the importance of solid compliance in the dynamics of blood flow in a mechanical heart valve. More importantly, they indicate that mechanical heart valves with compliant leaflets may have smaller regurgitant volumes and smaller shear stresses than the ones with rigid leaflets.     

Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve

The mitral valve, as an active flap, forms the major part of the left ventricular inflow tract and therefore plays an important function in many aspects of left ventricular performance. The anterior leaflet of this valve is the largest and most ventrally placed of two leaflets that come together during ventricular systole to close the left atrioventricular orifice. Various neurotransmitters are responsible for different functions including controlling valve movement, inhibiting or causing the failure of impulse conduction in the valve and the sensation of pain. Nitric oxide acts as a gaseous free radical neurotransmitter, neuromediator and effective cardiovascular modulator. Acetyl-choline is known to function as a typical neurotransmitter. Histochemical methods for detection of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), as an indirect nitric oxide-synthase marker, and method for detection of acetylcholinesterase (AChE) were used. Both methods were performed on the same valve sample. A widespread distribution of nerve fibres was observed in the anterior leaflet of the mitral valve. The fine NADPH-d positive (nitrergic) nerve fibres were identified in all zones of valve leaflet. AChE positive (cholinergic) nerve fibres were identified forming dense network and fibres organized in stripes. Endocardial cells and vessels manifested heavy NADPH-d activity. Our observations suggest a different arrangement of nitrergic and cholinergic nerve fibres in the anterior leaflet of the mitral valve. The presence of nitrergic and cholinergic activity confirms the involvement of both neurotransmitters in nerve plexuses and other structures of mitral valve.Key words: NADPH-diaphorase, acetylcholinesterase, heart, mitral valve, nerve fibres, vessels, rat.     

Outward sodium current in beating heart cells.

This article is a study of the fast Na current during action potentials. We have investigated the outward Na current (Mazzanti, M., and L.J. DeFelice. 1987. Biophys. J. 52:95-100) in more detail, and we have asked whether it goes through the same channels associated with the rapid depolarization phase of action potentials. We address the question by patch clamping single, spontaneously beating, embryonic chick ventricle cells, using two electrodes to record the action potential and the patch current simultaneously. The chief limitation is the capacitive current, and in this article we describe a new method to subtract it. Varying the potential and the Na concentration in the patch pipette, and fitting the corrected currents to a standard model (Ebihara, L., and E.A. Johnson. 1980. Biophys. J. 32:779-790), provides evidence that the outward current is carried by the same channels that conduct the inward current. We compare the currents in beating cells to currents in nonbeating cells using whole-cell and cell-attached patch clamp recordings. The latter tend to show more positive Na reversal potentials, with the implication that internal Na is higher in beating cells. We propose that the plateau of the action potential, which is partly due to an inward Ca current, exceeds Na action current reversal potentials, and that this driving force gives rise to an outward movement of Na ions. The existence of such a current would imply that the fast repolarization phase after the upstroke of cardiac action potentials is partly due to the Na action current.