AN OVINE MODEL OF ACUTE MYOCARDIAL-INFARCTION AND CHRONIC LEFT-VENTRICULAR DYSFUNCTION

In order to develop and validate an ovine model of myocardial infarcti on with subsequent impairment of left ventricular function, 15 instrum ented sheep underwent selective microembolization of the left coronary arteries with 0.5 mL 90 micron polystyrene beads. Hemodynamics and pl asma hormones were measured preembolization (baseline) and then at hou rs 2, 4, 6, and 12 and days 1, 2, 3, 5 and 7 postembolization. Of the 15 sheep studied, 2 (13%) died on the day of embolization from arrhyth mias. In the remaining sheep, left ventricular systolic pressure and s troke work (both P<0.001) were reduced promptly and remained below bas al levels. Mean arterial pressure (P<0.001) increased initially, then decreased to below basal levels by hour 6. Heart rate (P<0.001) and le ft atrial pressure (P<0.05) were increased while cardiac output was de creased (P<0.05). Left ventricular ejection fraction at day 7 was redu ced (38.8 +/-3.5 vs 46.0 +/-3.9% preembolization; P<0.05). The cardiac enzymes creatine kinase (P<0.001) and troponin-T (P<0.001) were incre ased following microembolization and returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain natriuretic peptides (bo th P<0.001) and plasma renin activity (P<0.005) were all increased fol lowing embolization. This ovine model mimics the hemodynamic and neuro humoral features of acute myocardial infarction, resulting in left ven tricular dysfunction, and should prove suitable for the study of inter ventions in a number of these conditions.