Altered collagen concentration in mitral valve leaflets: biochemical and finite element analysis

Ischemic mitral regurgitation or ventricular wall motion abnormalities will alter the stress distribution in the mitral valve. We hypothesize that in response, the regional collagen concentration will be altered and will significantly impact the stress distribution in the mitral valve.

Two sheep served as normal (sham) controls. Two other sheep had coronary ligation resulting in abnormal ventricular wall motion. Four sheep underwent ligation to infarct the posteromedial papillary muscle, resulting in ischemic regurgitation. After 4 or 8 weeks, the mitral valves were excised, and the anterior leaflet sections were subjected to an assay for collagen concentration. Next, in a finite element model, to simulate changes in collagen concentration, the tissue stiffness was increased by 20%, and then decreased by 20%. In another model, the thickness of the tissue was increased by 20%, and then combined with decreased tissue stiffness. Physiologic loading pressures were applied, and leaflet stress, chordal stress, and coaptation results were analyzed.

The average collagen concentration in the normal sheep leaflets was 59.2% (dry weight), 50.6% in the ischemic controls, and 45.8% in the papillary muscle infarct group. Collagen concentration was greatest at the midline and decreased toward the commissures. Increased tissue stiffness resulted in increased leaflet and chordal stresses, as well as reduced coaptation. Decreased stiffness resulted in the opposite. Increased tissue thickness reduced leaflet and chordal stresses, but also reduced coaptation. The combination of increased tissue thickness and decreased stiffness demonstrated the greatest reduction in leaflet and chordal stress, while maintaining normal leaflet coaptation.

The observed changes may demonstrate an early effort to compensate for increased leaflet stress. Microstructural alterations may demonstrate an early effort to compensate for altered physiologic loading to reduce stress and maintain coaptation. It is crucial in repairing or partially replacing thickened tissue that normal geometry and physiology be restored.