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

Abstract

Introduction: Plasma B-type natriuretic peptide concentration (BNP) is a marker of cardiac dysfunction [1]. It is unclear whyextremely high concentrations have been reported in sepsis with preserved systolic function [2]. This study sought to evaluaterelationships 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).Conclusions: In this model, sepsis was associated with echocardiographic evidence of diastolic dysfunction resemblingclinical sepsis without an associated increase in BNP. HR was an independent predictor of BNP, accounting for 56% of variation.