Active stiffening of mitral valve leaflets in the beating heart

Abstract

The anterior leaflet of the mitral valve (MV), viewed traditionally as a passive membrane, is shown to be a highly active structure in the beating heart. Two types of leaflet contractile activity are demonstrated: 1) a brief twitch at the beginning of each beat (reflecting contraction of myocytes in the leaflet in communication with and excited by left atrial muscle) that is relaxed by midsystole and whose contractile activity is eliminated with β-receptor blockade and 2) sustained tone during isovolumic relaxation, insensitive to β-blockade, but doubled by stimulation of the neurally rich region of aortic-mitral continuity. These findings raise the possibility that these leaflets are neurally controlled tissues, with potentially adaptive capabilities to meet the changing physiological demands on the heart. They also provide a basis for a permanent paradigm shift from one viewing the leaflets as passive flaps to one viewing them as active tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to MV disease, but even the definitions of MV disease itself.

Electromechanical coupling between the atria and mitral valve

“…We have previously shown edge stiffening to be unaffected by ␤-blockade or neural stimulation (5) and in the present study now show it to be unaffected by loss of atrial depolarization, as well. The hypothesis of Krishnamurthy et al (8) suggests that a change in shape of the AL edge, brought about by the initial contact between the AL and PL during IVC, provides geometric stiffening of the AL edge, in that subsequent pressure changes acting on this new edge geometry produce reduced leaflet-edge displacements relative to those observed with the same pressure change later in systole.…”

“…As previously described (5), cardiac cycle timing and finite-element models of the AL were individually defined for each beat using matched IVC and IVR pressure intervals for that beat. The initial geometry for each model was defined by the coordinate values for each leaflet, annular and papillary tip marker at the reference states used in previous analyses (5,8). A leaflet surface was generated from leaflet and annular marker positions.…”

“…This contraction is also believed to be the cellular basis for the substantial AL stiffening observed during isovolumic contraction (IVC) (5). Such stiffening, observed primarily as a stiffening transient in the annular third of the AL (8), subsides by isovolumic relaxation (IVR) (9).…”

Modeling active muscle contraction in mitral valve leaflets during systole: a first approach

“…This indicates that something is missing in the model. There are several investigations that have documented both muscle fibers, muscle cells, and innervation in the mitral leaflets (Wit et al 1979;Filip et al 1986;Sonnenblick et al 1967;Curtis and Priola 1992;Montiel 1970;DeBiasi et al 1984;Kawano et al 1993;Marron et al 1996;Timek et al 2003;Itoh et al 2009). It can be convincingly argued that these tissues should have an active role in the mitral valve motion (Williams and Jew 2003;Itoh et al 2009), and is one part of the model that is missing in order to obtain the flat shape of the leaflets at peak systole instead of the bulging.…”

Anterior mitral leaflet curvature in the beating ovine heart: a case study using videofluoroscopic markers and subdivision surfaces

“…These are orthogonal to the directions of minimum curvature n(κ min ), which, in turn, might be correlated to the preferred microstructural orientations of the leaflet, see, e.g., Kunzelman and Cochran (1992), Itoh et al (2009), for a discussion on leaflet anisotropy, histological staining, and a conceptual model of the leaflet microstructure, respectively.…”