Ischemia-Induced Model of Diastolic Dysfunction in Sheep

ABSTRACT

Background: Ischemic heart failure with normal ejection fraction (HFNEF) is an increasingly recognized entity that carries similar morbidity and mortality than low ejection fraction heart failure. Animal models of diastolic dysfunction mimicking this condition are lacking and are essential for the development of therapeutic strategies. Methods and Results: Eight Corriedale sheep, 18 ± 5 months old, were included in the study. Basal echocardiography and myocardial perfusion evaluation (SPECT) was performed. Acute myocardial infarction (AMI) was made by occlusion (90 min) and reperfusion of the second diagonal branch of the anterior descending coronary artery. Two months after AMI, echocardiography and SPECT evaluation were performed prior to sacrifice. Basal and 2 months echocardiography showed similar fractional shortening and ventricular dimensions in each animal except for an increase in left atrial diameter. No mitral regurgitation was evidenced. SPECT imaging and pathology confirmed infarction in the apical, apico-anterior, and apico-septal segments. Conclusion: A novel model of ischemia-induced diastolic dysfunction with preserved ventricular thickness and ejection fraction is described. This model opens the possibility of testing therapeutic options for patients with this condition.

Keywords: :

• animal models of disease
• acute myocardial infarction
• diastolic dysfunction
• single photon emission tomography
• echocardiography
• systolic dysfunction