LARGE ANIMAL-MODEL OF ISCHEMIC MITRAL REGURGITATION

A large animal model of ischemic mitral regurgitation (MR) that resemb les the multiple presentations of the human disease was developed in s heep. In 76 sheep hearts, the anatomy of the coronary arterial circula tion was determined by observation and polymer casts. Two variations, types A and 8, which differed by the vessel that supplied the left ven tricular apex, were found. In all hearts, the circumflex coronary arte ry has three marginal branches and terminates in the posterior descend ing 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 n ot infarct either papillary muscle, significantly (p < 0.001) increase s LV cavity size 48% at the high papillary muscle level by 8 weeks, an d does not cause MR. Ligation of the second and third marginal branche s infarcts 21.4% +/- 4.0% of the LV mass, includes the posterior papil lary muscle, significantly increases (p < 0.001) LV cavity size 75%, a nd causes severe MR by 8 weeks. Ligation of the second and third margi nal branches and the posterior descending coronary artery infarcts 35% to 40% of the LV mass, increases LV cavity size 39% within 1 hour, an d causes massive MR. After moderate (21% to 23%) LV infarction, develo pment of ischemic MR requires both LV dilatation and posterior papilla ry muscle infarction; neither condition alone produces MR. Large poste rior wall infarctions (35% to 40%) that include the posterior papillar y muscle produce immediate, severe MR. This sheep model of ischemic MR reproduces the acute and chronic presentations of the clinical diseas e without injury to the anatomic subunits of the valve. The model indi cates that altered ventricular geometry and changes in the spatial rel ationship between the infarcted papillary muscle and other components of the valve are of primary importance in the development of ischemic MR.