Left Ventricular Diastolic Filling Characteristics Are Not Impaired but Systolic Performance Was Augmented in the Early Hours of Experimental Endotoxemia in Humans

Abstract

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.

Myocardial depression in sepsis: From pathogenesis to clinical manifestations and treatment

“…In these patients, all abnormalities recovered within 7 days after sepsis resolution. In contrast, Marthu et al [94] observed no diastolic dysfunction during a 5-hour endotoxin infusion in healthy volunteers. A recent study in which 262 patients with severe sepsis and septic shock were studied [95] showed that diastolic dysfunction was not only common but also that it represented a major predictor of mortality in this setting.…”

Sepsis-induced Cardiomyopathy

“…In patients with diastolic dysfunction prior to the SIMD, difficult weaning from mechanical ventilation and increased need for inotropic support could be predicted [43, 44]. Mathru and coworkers [45], in a case-control pilot study with a group of 11 young people (aged 30 ± 6 years), previously healthy and endotoxin-challenged volunteers who had not received empirical volume loading, despite stating that knowledge of diastolic function status could be very helpful to predict how a septic patient would respond to changes in preload, didn´t find statistically significant differences in diastolic function with the control group. The authors found significant increase in wave A and E/A ratio after-endotoxin infusion and no significant changes from baseline in the E wave (p <0.05).…”

Cardiovascular Responses During Sepsis

“…The studies above clearly show that 4-6 ng kg -1 of LPS in healthy human subjects are able to induce a hyperdynamic state characterized by a tendency for hypotension, a markedly decreased SVR and elevated CO at constant (352,506) or decreased preload (322,326). As it will be discussed, contractility is increased (326) or unchanged at 3 hours (506), and, at 5 hours, unaltered (326) or depressed in the presence of volume loading (265,322,506).…”

“…In terms of Guyton's equilibrium diagram, the increase of CO at constant or decreased C P observed in LPS-treated healthy volunteers (326,352,506) implies a change of both the functional properties of the systemic circulation and of the heart. In Figure 5 the equilibrium point before the LPS injection is point A corresponding to a CO of 5.5 L min -1 and a CVP of 5 mmHg.…”

“…Broken lines show the effects of endotoxin. In healthy volunteers, without fluid loading, LPS causes an increase of cardiac output (CO) at constant (506) or decreased (322,326) central venous pressure (CVP). The former possibility is shown by operating point E, which univocally implies a counterclockwise rotation of the cardiac function curve (from CFC c to CFC e ).…”