Active stiffening of mitral valve leaflets in the beating heart.

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 beta-receptor blockade and 2) sustained tone during isovolumic relaxation, 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 MV disease, but even the definitions of MV disease itself.

[1]  F. Yin,et al.  Biaxial mechanical behavior of excised porcine mitral valve leaflets. , 1995, The American journal of physiology.

[2]  J. Jew,et al.  Is the mitral valve passive flap theory overstated? An active valve is hypothesized. , 2004, Medical hypotheses.

[3]  H. Woollard The Innervation of the Heart. , 1926, Journal of anatomy.

[4]  P. McCarthy,et al.  Mitral valve stiffening in end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation. , 2005, The Journal of thoracic and cardiovascular surgery.

[5]  Magdi H. Yacoub,et al.  The cardiac valve interstitial cell. , 2003, The international journal of biochemistry & cell biology.

[6]  E. Sonnenblick,et al.  An Intrinsic Neuromuscular Basis for Mitral Valve Motion in the Dog , 1967, Circulation research.

[7]  M. Simionescu,et al.  Interstitial Cells of the Heart Valves Possess Characteristics Similar to Smooth Muscle Cells , 1986, Circulation research.

[8]  R. A. Murphy,et al.  Length‐Tension Relationship of Smooth Muscle of the Hog Carotid Artery , 1973, Circulation research.

[9]  M R de Leval,et al.  Innervation of human atrioventricular and arterial valves. , 1996, Circulation.

[10]  B. Pieske,et al.  Ca(2+) handling in isolated human atrial myocardium. , 2000, American journal of physiology. Heart and circulatory physiology.

[11]  T. Cooper,et al.  Electrical activity of the canine mitral valve in situ. , 1969, The American journal of physiology.

[12]  S. Biasi,et al.  Histochemical and ultrastructural study on the innervation of human and porcine atrio-ventricular valves , 2004, Anatomy and Embryology.

[13]  K S Kunzelman,et al.  Nondestructive analysis of mitral valve collagen fiber orientation. , 1991, ASAIO transactions.

[14]  R. B. Smith Intrinsic innervation of the atrioventricular and semilunar valves in various mammals. , 1971, Journal of anatomy.

[15]  M. M. Montiel Muscular apparatus of the mitral valve in man and its involvement in left-sided cardiac hypertrophy. , 1970, The American journal of cardiology.

[16]  Malcolm R. Miller,et al.  STUDIES ON THE NERVE ENDINGS IN THE HEART. , 1964, The American journal of anatomy.

[17]  S. Kawai,et al.  Morphological study on vagal innervation in human atrioventricular valves using histochemical method. , 1993, Japanese circulation journal.

[18]  R. A. Murphy,et al.  Force‐Velocity and Series Elastic Characteristics of Smooth Muscle from the Hog Carotid Artery , 1974, Circulation research.

[19]  Magdi H. Yacoub,et al.  Localization and pattern of expression of extracellular matrix components in human heart valves. , 2005, The Journal of heart valve disease.

[20]  Mark Eastwood,et al.  Force generation of different human cardiac valve interstitial cells: relevance to individual valve function and tissue engineering. , 2007, The Journal of heart valve disease.

[21]  P. Dagum,et al.  Ablation of mitral annular and leaflet muscle: effects on annular and leaflet dynamics. , 2003, American journal of physiology. Heart and circulatory physiology.

[22]  G. Mitchell THE INNERVATION OF THE HEART , 1953, British heart journal.

[23]  Y. Fung,et al.  Mechanical properties of isolated mammalian ureteral segments. , 1971, The American journal of physiology.

[24]  J. Jew,et al.  Tyrosine hydroxylase- and nitric oxide synthase-immunoreactive nerve fibers in mitral valve of young adult and aged Fischer 344 rats. , 1996, Journal of the autonomic nervous system.

[25]  T Cooper,et al.  Structural basis of cardiac valvar function. , 1966, Archives of surgery.

[26]  O. Johansson,et al.  Distribution of PGP 9.5, TH, NPY, SP and CGRP immunoreactive nerves in the rat and guinea pig atrioventricular valves and chordae tendineae , 1997, Journal of anatomy.

[27]  R. P. Cochran,et al.  Stress/Strain Characteristics of Porcine Mitral Valve Tissue: Parallel Versus Perpendicular Collagen Orientation , 1992, Journal of cardiac surgery.

[28]  A. Chester,et al.  Molecular and functional characteristics of heart-valve interstitial cells , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[29]  J Günter Grossmann,et al.  Collagen organization in canine myxomatous mitral valve disease: an x-ray diffraction study. , 2007, Biophysical journal.

[30]  W. Nagel Handbuch der Physiologie des Menschen. , 1905 .

[31]  U. Stenevi,et al.  Adrenergic and non-adrenergic valvular nerves of the heart , 2005, Experientia.

[32]  Smith Rb Intrinsic innervation of the atrioventricular and semilunar valves in various mammals. , 1971 .

[33]  A. L. Wit,et al.  Electrophysiological Properties of Cardiac Muscle in the Anterior Mitral Valve Leaflet and the Adjacent Atrium in the Dog: POSSIBLE IMPLICATIONS FOR THE GENESIS OF ATRIAL DYSRHYTHMIAS , 1973, Circulation research.

[34]  R. Hibbs,et al.  The atrioventricular valves of the guinea-pig. II. An ultrastructural study. , 1973, The American journal of anatomy.

[35]  F. Guilak,et al.  Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. , 2006, American journal of physiology. Heart and circulatory physiology.

[36]  Daniel B Ennis,et al.  Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis. , 2008, American journal of physiology. Heart and circulatory physiology.

[37]  R. Hibbs,et al.  The atrioventricular valves of the guinea-pig. I. A light microscopic study. , 1973, The American journal of anatomy.

[38]  Karen May-Newman,et al.  The structure and mechanical properties of the mitral valve leaflet-strut chordae transition zone. , 2004, Journal of biomechanical engineering.

[39]  D. V. Priola,et al.  Mechanical activity of canine mitral valve in situ. , 1970, The American journal of physiology.

[40]  T. Williams,et al.  Variations in atrioventricular valve innervation in four species of mammals. , 1990, The American journal of anatomy.

[41]  T. Tsumori,et al.  Ultrastructural evidence for innervation of the endothelium and interstitial cell in the atrioventricular valves of the Japanese monkey , 1994, The Anatomical record.

[42]  T. H. Williams FAST-CONDUCTING FIBRES IN THE MITRAL VALVE , 1964, British heart journal.

[43]  T. H. Williams MITRAL AND TRICUSPID VALVE INNERVATION , 1964, British heart journal.

[44]  Andrew L. Wit,et al.  Canine Mitral Complex: ULTRASTRUCTURE AND ELECTROMECHANICAL PROPERTIES , 1972, Circulation research.

[45]  A. L. Wit,et al.  Ultrastructure and Transmembrane Potentials of Cardiac Muscle in the Human Anterior Mitral Valve Leaflet , 1979, Circulation.

[46]  B. Ehinger,et al.  Adrenergic and cholinesterase-containing neurons of the heart , 2004, Histochemie.

[47]  I. Taylor,et al.  Atrioventricular and semilunar valve vascularization in rabbits and guinea pigs. , 1971, Acta anatomica.