An Ovine Model of Acute Myocardial Infarction and Chronic Left Ventricular Dysfunction

Abstract

In order to develop and validate an ovine model of myocardial infarction with subse quent impairment of left ventricular function, 15 instrumented sheep underwent selective microembolization of the left coronary arteries with 0.5 mL 90 micron polystyrene beads. Hemodynamics and plasma hormones were measured preembolization (baseline) and then at hours 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 arrhythmias. In the remaining sheep, left ventricular systolic pressure and stroke work (both P<0.001 ) were reduced promptly and remained below basal levels. Mean arterial pressure (P<0.001) increased initially, then decreased to below basal levels by hour 6. Heart rate (P<0.001) and left atrial pressure (P<0.05) were increased while cardiac output was decreased (P<0.05). Left ventricular ejection fraction at day 7 was reduced (38.8 ±3.5 vs 46.0 ±3.9% preem bolization ; P<0.05). The cardiac enzymes creatine kinase (P<0.001) and troponin-T (P< 0.001) were increased following microembolization and returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain natriuretic peptides (both P< 0.001) and plasma renin activity (P<0.005) were all increased following embolization. This ovine model mimics the hemodynamic and neurohumoral features of acute myocardial infarction, resulting in left ventricular dysfunction, and should prove suitable for the study of interventions in a number of these conditions.