COLLAGEN-SYNTHESIS IS UP-REGULATED IN MITRAL-VALVES SUBJECTED TO ALTERED STRESS

Mitral regurgitation (MR) and abnormal ventricular wall motion (AVWM) are two cardiac conditions that may increase mitral valve (MV) stresse s. Theoretically, increased stress could induce damaging MV tissue alt erations. These alterations may impair the preferred option of repair, and mandate replacement. It is hypothesized that MV collagen synthesi s is upregulated in response to MR and AVWM. To test this hypothesis i n a pilot study, an ischemic sheep model (n = 8) was employed. Four sh eep underwent selective coronary artery ligation to infarct a papillar y muscle, which resulted in MR. Two other sheep underwent similar coro nary ligation to create AVWM. As controls, two sheep underwent sham su rgery (no ligation). Sheep were killed 4 or 8 weeks post operatively a nd their MVs were sectioned. Sections were stained with an antibody (S P1.D8, University of Iowa) to procollagen I (precursor to collagen I). The percent area of procollagen stain present was measured by image a nalysis (Optimas Corporation) and used as an indicator of collagen syn thesis. Procollagen results indicated that MV collagen synthesis was u pregulated by a factor of 1.8 in both the MR and AVWM groups versus co ntrols. In addition, results showed greater upregulation in anterior l eaflets compared with posterior leaflets in both infarct groups. These results indicate that MV collagen synthesis is upregulated in respons e to MR and AVWM.