LARGE ANIMAL-MODEL OF ISCHEMIC MITRAL REGURGITATION

A large animal model of ischemic mitral regurgitation (MR) that resembles the multiple presentations of the human disease was developed in sheep. In 76 sheep hearts, the anatomy of the coronary arterial circulation was determined by observation and polymer casts. Two variations, types A and 8, which differed by the vessel that supplied the left ventricular apex, were found. In all hearts, the circumflex coronary artery has three marginal branches and terminates in the posterior descending coronary artery. The amount and location of left ventricular (LV) mass supplied by each marginal circumflex branch was determined by dye injection and planimetry. In type A hearts, ligation of the first and second marginal branches infarcts 23% +/- 3.0% of the LV mass, does not infarct either papillary muscle, significantly (p < 0.001) increases LV cavity size 48% at the high papillary muscle level by 8 weeks, and does not cause MR. Ligation of the second and third marginal branches infarcts 21.4% +/- 4.0% of the LV mass, includes the posterior papillary muscle, significantly increases (p < 0.001) LV cavity size 75%, and causes severe MR by 8 weeks. Ligation of the second and third marginal branches and the posterior descending coronary artery infarcts 35% to 40% of the LV mass, increases LV cavity size 39% within 1 hour, and causes massive MR. After moderate (21% to 23%) LV infarction, development of ischemic MR requires both LV dilatation and posterior papillary muscle infarction; neither condition alone produces MR. Large posterior wall infarctions (35% to 40%) that include the posterior papillary muscle produce immediate, severe MR. This sheep model of ischemic MR reproduces the acute and chronic presentations of the clinical disease without injury to the anatomic subunits of the valve. The model indicates that altered ventricular geometry and changes in the spatial relationship between the infarcted papillary muscle and other components of the valve are of primary importance in the development of ischemic MR.