Sepsis-associated diastolic dysfunction without elevated plasma B-type natriuretic peptide

Introduction

Plasma B-type natriuretic peptide concentration (BNP) is a marker of cardiac dysfunction [1]. It is unclear why extremely high concentrations have been reported in sepsis with preserved systolic function [2]. This study sought to evaluate relationships between BNP and in vivo diastolic function in a rat cecal ligation and perforation (CLP) model of sepsis.

Methods

With institutional ethics committee approval (UQ AEC Protocol 675/05), 24 male Sprague–Dawley rats (518 ± 56 g) were studied. Rats were assigned to CLP (n = 12), sham surgery (sham, n = 6) or anaesthesia without surgery (control, n = 6). Echocardiography (15 MHz rodent probe) and venous blood sampling (BNP enzyme immunoassay) were performed prior to intervention (baseline; T0) and 18–22 hours following intervention (final; T2).

Results

Prior to final evaluation, three CLP rats (25%) and one sham rat (during anaesthesia) died. Baseline differences between groups (ANOVA) were demonstrated for heart rate (HR) (CLP 340 ± 36 bpm, sham 351 ± 19 bpm, control 300 ± 12 bpm; P = 0.02), peak passive to active diastolic transmitral velocity ratio (E/A) (CLP 1.7 ± 0.65, sham 1.26 ± 0.27, control 2.34 ± 0.59; P = 0.048) and A velocity (CLP 0.574 ± 0.13 m/s, sham 0.733 ± 0.33 m/s, control 0.411 ± 0.07 m/s; P = 0.03). BNP was not significantly different between groups (CLP 0.676 ± 0.179 ng/ml; sham 0.719 ± 0.202 ng/ml; control 0.503 ± 0.006 ng/ml; P = 0.07). At T2, CLP was compared with sham and control (ANCOVA with adjustment for baseline values). Compared with control rats, CLP rats demonstrated higher HR (CLP 402 ± 46 bpm, control 305 ± 11 bpm; P = 0.003), higher A velocity (CLP 0.802 ± 0.152 m/s, control 0.501 ± 0.103 m/s; P = 0.01), and lower E/A (CLP 1.02 ± 0.23, control 1.74 ± 0.46; P = 0.004). BNP was not significantly different in the CLP group (CLP 0.743 ± 0.225 ng/ml, sham 0.756 ± 0.213 ng/ml (P = 0.3), control 0.509 ± 0.026 ng/ml (P = 0.7)). At T2, multiple linear regression with backward elimination yielded HR as the only independent predictor of BNP (adjusted r² = 0.56, P < 0.001).

Conclusion

In this model, sepsis was associated with echocardiographic evidence of diastolic dysfunction resembling clinical sepsis without an associated increase in BNP. HR was an independent predictor of BNP, accounting for 56% of variation.