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Regional differences in wall motion and wall thickening were quantitated in the normal left ventricle using two-dimensional echocardiography (2-D echo). Using a computer-aided system, the left ventricle was subdivided in a standardized manner into 40 segments of five 2-D echo short-axis cross sections from the mitral valve level to the low left ventricle or apex. Measurements of sectional and segmental cavity areas, muscle areas and endocardial as well as epicardial peritneters, allowed assessment of contractile function using such indexes as endocardial systolic fractional area change (FAC), wall thickening (WTh), and circumferential fiber shortening (shortening). In 50 normal anesthetized, closed-chest dogs (including 10 studies in the conscious state) and in 32 normal humans, left ventricular contractile function increased significantly from base to apex. Thus, in anesthetized dogs, sectional FAC, WTh and shortening increased from left ventricular base to apex as follows: 39.4 ± 5.1% to 61.6 ± 7.2%, 20.5 ± 6.6% to 46.7 11.5% and 22.7 ± 3.4% to 35.4 5.9%, respectively. Similar trends were noted in conscious dogs. In man, sectional FAC, WTh and shortening also increased from the mitral valve to the low left ventricular level: 38.8 3.3% to 60.7 4.5%, 23.9 ± 5.6% to 28.9 ± 7.6% and 21.4 ± 5.0% to 30.6 ± 5.6%, respectively. Detailed segmental analysis in individual cross sections also revealed regional differences in contraction. Generally, contraction was most vigorous in posterior regions of the left ventricle. The septal regions exhibited lowest contraction at the base, but also the greatest increase from base to apex, both in the canine and human. Lateral regions did not show significant changes along the length of the left ventricle. Diastolic wall thickness also varied. We conclude that contraction in the normal left ventricle cannot be assumed to be uniform or symmetrical. These normal regional differences in function should be taken into account when evaluating altered physiologic states and in studying effects of therapeutic interventions.