EXPERIMENTAL-MODEL OF CHRONIC GLOBAL LEFT-VENTRICULAR DYSFUNCTION SECONDARY TO LEFT CORONARY MICROEMBOLIZATION

A model of chronic left ventricular dysfunction characterized by left ventricular dilation, elevated filling pressures and histologic changes has been lacking. In this study the use of coronary microsphere embolization-induced ischemia was explored as a method of producing chronic left ventricular dysfunction. Acute ischemic left ventricular dysfunction was induced in 13 mongrel dogs with 50-mu-m plastic microspheres until the peak positive first derivative of left ventricular pressure (dP/dt) decreased by 25% and the left ventricular end-diastolic pressure increased to greater-than-or-equal-to 12 mm Hg. After 8 weeks of observation, hemodynamic and echocardiographic variables were measured in each dog. Acute left ventricular dysfunction resulted in a dilated left ventricle with systolic dysfunction (area ejection fraction 24 +/- 6% vs. 57 +/- 9% initially, p < 0.01) and elevated left ventricular filling pressures. Isovolumetric relaxation was prolonged and the peak rapid filling/atrial filling velocity and integral ratios were reduced. Eight weeks after embolization, there was an increased left ventricular size (end-diastolic area 15.1 +/- 2.1 cm2 at 8 weeks vs. 13.5 +/- 1.4 cm2 early after microsphere injection, p < 0.05), unchanged end-systolic area, improved area ejection fraction and increased left ventricular mass. Left ventricular end-diastolic pressure increased and, despite continued abnormal relaxation, the peak rapid filling/atrial filling velocity and integral ratios increased to above baseline values, demonstrating a "restrictive" pattern. Gross and histologic examination revealed diffuse, patchy scarring associated with perivascular fibrosis. Thus, coronary microsphere embolization resulted in a model of chronic moderate left ventricular systolic dysfunction and abnormal diastolic function characterized by a "restrictive" filling pattern.