TY - JOUR
T1 - Evidence of adaptive mitral leaflet growth
AU - Rausch, Manuel K.
AU - Tibayan, Frederick A.
AU - Craig Miller, D.
AU - Kuhl, Ellen
N1 - Funding Information:
We thank Paul Chang for technical assistance and Maggie Brophy for careful marker image digitization, and George T. Daughters III for computation of 4D data from biplane 2D marker coordinates. This work was supported in part by the National Institutes of Health grants R01 HL29589 and R01 HL67025 to D. Craig Miller, and by the National Science Foundation CAREER award CMMI-0952021 to Ellen Kuhl.
PY - 2012
Y1 - 2012
N2 - Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. Recent studies suggest that mitral leaflets have the potential to grow and reduce the degree of regurgitation. Leaflet growth has been associated with papillary muscle displacement, but role of annular dilation in leaflet growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced by papillary muscle tethering and annular dilation, triggers chronic leaflet growth. To decipher the mechanisms that drive the growth process, we further quantified regional and directional variations of growth. Five adult sheep underwent coronary snare and marker placement on the left ventricle, papillary muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the snares to create inferior myocardial infarction. We recorded marker coordinates at baseline, acutely (immediately post-infarction), and chronically (five weeks post-infarction). From these coordinates, we calculated acute and chronic changes in ventricular, papillary muscle, and annular geometry along with acute and chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p< 0.001) induced chronic posterior papillary muscle displacement of 13.49. mm (p=0.07). Chronic mitral annular area, commissural and septal-lateral distances increased by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area, circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non-significant regional variations (p=0.868). Our study demonstrates that mechanical stretch, induced by annular dilation and papillary muscle tethering, triggers mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may open new avenues to pharmacologically or surgically manipulate mechanotransduction pathways to augment mitral leaflet area and reduce the degree of regurgitation.
AB - Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. Recent studies suggest that mitral leaflets have the potential to grow and reduce the degree of regurgitation. Leaflet growth has been associated with papillary muscle displacement, but role of annular dilation in leaflet growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced by papillary muscle tethering and annular dilation, triggers chronic leaflet growth. To decipher the mechanisms that drive the growth process, we further quantified regional and directional variations of growth. Five adult sheep underwent coronary snare and marker placement on the left ventricle, papillary muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the snares to create inferior myocardial infarction. We recorded marker coordinates at baseline, acutely (immediately post-infarction), and chronically (five weeks post-infarction). From these coordinates, we calculated acute and chronic changes in ventricular, papillary muscle, and annular geometry along with acute and chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p< 0.001) induced chronic posterior papillary muscle displacement of 13.49. mm (p=0.07). Chronic mitral annular area, commissural and septal-lateral distances increased by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area, circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non-significant regional variations (p=0.868). Our study demonstrates that mechanical stretch, induced by annular dilation and papillary muscle tethering, triggers mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may open new avenues to pharmacologically or surgically manipulate mechanotransduction pathways to augment mitral leaflet area and reduce the degree of regurgitation.
KW - Cardiac mechanics
KW - Growth
KW - Mitral leaflet
KW - Mitral valve
KW - Regurgitation
KW - Remodeling
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U2 - 10.1016/j.jmbbm.2012.07.001
DO - 10.1016/j.jmbbm.2012.07.001
M3 - Article
C2 - 23159489
AN - SCOPUS:84868670461
SN - 1751-6161
VL - 15
SP - 208
EP - 217
JO - Journal of the Mechanical Behavior of Biomedical Materials
JF - Journal of the Mechanical Behavior of Biomedical Materials
ER -