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Am J Physiol Heart Circ Physiol (April 10, 2009). doi:10.1152/ajpheart.00120.2009
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00120.2009v1
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Submitted on February 4, 2009
Revised on March 9, 2009
Accepted on April 3, 2009

ACTIVE STIFFENING OF MITRAL VALVE LEAFLETS IN THE BEATING HEART

Akinobu Itoh1, Gaurav Krishnamurthy1, Julia C. Swanson1, Daniel B Ennis2, Wolfgang Bothe, Ellen Kuhl1, Matts Karlsson3, Lauren R. Davis, D. Craig Miller4, and Neil B. Ingels, Jr.5*

1 Stanford University
2 UCLA
3 Linköping University
4 Falk Cardiovascular Research Center
5 Research Institute of the Palo Alto Medical Foundation

* To whom correspondence should be addressed. E-mail: ingels{at}stanford.edu.

The anterior leaflet of the mitral valve, 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: 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) which is relaxed by mid-systole and whose contractile activity is eliminated with {beta}-receptor blockade; and sustained tone during IVR, insensitive to {beta}-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 mitral valve disease, but even the definitions of mitral valve disease itself.







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