This study was performed to determine whether endotoxemia causes diastolic cardiac dysfunction. Eleven healthy volunteers, 30 ± 6 years of age, underwent comprehensive transthoracic echocardiographic assessment including two-dimensional, M-mode transmitral and tissue Doppler of systolic and diastolic function at baseline and at 3 and 5 h after intravenous administration of purified Escherichia coli endotoxin (4 ng/kg). Data were analyzed by analysis of variance; P values of less than 0.05 were considered significant. Endotoxin administration resulted in a hyperdynamic state characterized by decreased mean arterial pressure and significant increase in cardiac index. This was accompanied by increases in several load-dependent systolic performance indices (3 and 5 h). Robust increases in peak systolic blood pressure/end-systolic volume index, one of the relatively load-independent contractility parameter, were also observed at 3 h after endotoxin administration. Transmitral peak early velocity (E), which represents early filling, significantly increased at 3 h after infusion. Late diastolic velocity (A), which represents atrial contraction, significantly increased at 3 and 5 h after infusion. The E/A ratio indicative of delayed relaxation significantly decreased due to increases in A (transmitral) and A (tissue Doppler) at 3 and 5 h after infusion. As expected, endotoxin infusion resulted in a hyperdynamic state associated with increases in systolic function indices including endocardial systolic velocities. The observed decreases in E/A (transmitral) and E/A (tissue Doppler) ratio were primarily due to increases in A and A. Moreover, isovolumic relaxation time and time constant for left ventricular relaxation, a load-independent parameter for ventricular relaxation, remained unchanged at 3 and 5 h after endotoxin infusion. Therefore, our findings are more likely due to enhanced atrial contractility resulting from increased sympathetic activity in response to reduction in left ventricular afterload and not due to altered diastolic filling characteristics. Copyright © 2006 by the Shock Society.