The objectives of this study were to define the spectrum of regional myocardial function changes during acute ischemia in closed chest animals by using newly developed ultrasonic strain rate and strain indexes derived from regional color Doppler myocardial imaging (CDMI) velocity data. Myocardial ischemia was induced in 18 pigs either with acute total 20-second occlusions (group 1, n = 12) or graded hypoperfusion (40 to 0 mL/min, group 2, n = 6) of the circumflex coronary artery. In addition, a dobutamine challenge (5 to 10 μg/kg per minute) was performed during sustained subtotal ischemia (10 mL/min) in group 2. CDMI acquisitions with parasternal views monitored the myocardial posterior wall function. Regional radial strain rate and strain (ϵ_r) were measured for systole, isovolumic relaxation, early diastole, and atrial filling, respectively. During total and graded ischemia, ϵ_r profiles were consistently modified, showing a delayed onset and a decrease in regional systolic thickening as well as increased postsystolic thickening. Radial strain rate and ϵ_r indexes decreased consistently during systole and early diastole and increased during isovolumic relaxation. End-systolic ϵ_r could differentiate total ischemia from severe hypoperfusion (10 mL/min), decreasing from 32% ± 8% to 16% ± 5% (versus 60% ± 10% at baseline). During dobutamine infusion (10 μg/kg per minute), end-systolic ϵ_r tended to decrease from 27% ± 5% to 18% ± 11%, whereas postsystolic thickening increased by 2-fold (P < .05). The combined analysis of regional deformation characteristics and global cardiac event timing derived from CDMI data can identify and quantify regional function changes induced by experimental acute ischemia in closed chest pigs. This would appear to be a potentially promising new noninvasive approach to the clinical evaluation of ischemia-induced changes in segmental myocardial function. (J Am Soc Echocardiogr 2001;14:874-84.)