Selective microembolization of the circumflex coronary artery in an ovine model: Dilated, ischemic cardiomyopathy and left ventricular dysfunction

Background: Ventricular remodeling often occurs after myocardial infarction, yet the natural history remains unpredictable because of the chronicity of the process and therapeutic interventions involved. We induced cardiac dysfunction in an ovine model via selective microembolization of the circumflex coronary artery (LCx) to test the hypothesis that ventricular remodeling progresses following coronary microembolization for up to 24 months. Methods and Results: Sheep underwent weekly selective microembolization of the LCx until left ventricular ejection fraction stabilized <35% for 2 consecutive weeks. In a subgroup carried out to 4 months, the end-systolic pressure-volume relationship slope decreased from 2.3 +/- 0.6 (baseline) to 1.3 +/- 0.5 at month 4 (P <.05). In a second group, echocardiography at 24 months, the ejection fraction decreased from 51 +/- 3% (baseline) to 25 +/- 2% (month 5) (P <.05) and stabilized through month 24 (23 +/- 5%, P <.05), whereas left ventricular end-systolic area and left ventricular end-diastolic area increased by 222% and 98%, respectively, through month 24. Conclusions: Selective microembolization of the LCx induces left ventricular dysfunction followed by dilated, ischemic cardiomyopathy, which continues to progress for up to 2 years despite stabilization of left ventricular ejection fraction. This model of ventricular remodeling secondary to microinfarction may be a useful experimental platform for large animal heart failure investigations.