Prolonged left ventricular dysfunction induced by sequential multifocal ischemic infarcts in dogs

A method of creating multifocal ischemia in animals leading to left ventricular (LV) functional impairment is described. In a series of 10 mongrel dogs, electrodes were implanted in multiple branches of the coronary arteries. Subsequently, in seven animals, an 800-microA anodal current was applied for 3 h repeatedly over a span of 4-9 weeks. After current application, serum creatine kinase cardiac isoenzyme increased by 12.2 +/- 4.6 U/L (p less than 0.01) and ischemic electrocardiographic changes were consistently present. After an average of 10.7 current applications, all animals were tachypneic on mild exertion. Repeated measurement of LV function demonstrated a substantial reduction in cardiac reserve. No significant changes in three control animals were observed. The animals were sacrificed 80 days (range 49-108 days) after the initial current application. Presacrifice cineangiography and postmortem examination disclosed coronary artery occlusions, stenoses, recanalizations, and collateralization in the distributions expected on the basis of the time elapsed since electrode activation. In all cases, the myocardium exhibited diffuse fibrosis. This method reliably brings about multifocal myocardial ischemic changes in dogs and may provide a chronic LV failure model particularly suitable for the evaluation of LV assist systems.