Right ventricular loading leads to diastolic septal flattening in man without necessarily requiring right ventricular pressure to exceed left ventricular pressure. This observation suggested that the unstressed septal configuration is flat and that its normal concave shape is due to the left-to-right transseptal pressure gradient. To examine this hypothesis, we studied septal configuration by two-dimensional echocardiography in nine patients with normal global and regional left ventricular function during surgery for coronary artery disease. The transseptal pressure gradient was obtained from pulmonary capillary wedge pressure minus right atrial pressure. Measurements were obtained at control (open chest, intact pericardium [C]), with the pericardium open (OP), on cardiopulmonary bypass (CPB), and after cardiac arrest (CA). There were no changes in any measurements between C and OP or between CPB and CA. Left ventricular end-diastolic cavity area decreased from 16.5 +/- 2.1 cm2 at C to 11.1 +/- 4.5 cm2 after CPB, and further decreased to 8.9 +/- 3.5 cm2 after CA (p less than .001), yet the septum flattened, as shown by an increase in its radius of curvature from 1.7 +/- 0.5 cm during C to 2.5 +/- 0.7 cm after CPB, and to 2.9 +/- 1.0 cm after CA (p less than .001), or from 0.4 +/- 0.1 to 0.8 +/- 0.4 to 1.1 +/- 0.5 U (p less than .001) when normalized for cavity area. Diastolic transseptal pressure gradient was reduced from 4.1 +/- 2.3 mm Hg during C to 1.1 +/- 1.8 mm Hg after CPB, and to 0.5 +/- 1.4 mm Hg after CA (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)