Amidou Sissou Traore1, Thibault Leger2, Guilhem Pagès1, Lucie Cassagnes3,4, Azarnoush Kasra5, Jean-Marie Bonny1, and Luc Demaison2,6
1UR270 QuaPA, INRA, Saint-Genès Champanelle, France, 2UNH, INRA, Clermont-Ferrand, France, 3Department of diagnostic and interventional radiology, Clermont Ferrand University Hospital, Clermont-Ferrand, France, 4IGT, Institut Pascal, UMR 6602, CNRS, Clermont-Ferrand, France, 5Heart Surgery Department, Clermont Ferrand University Hospital, Clermont-Ferrand, France, 6CRNH, Clermont Auvergne University, Clermont-Ferrand, France
Synopsis
Severe sepsis is one of the leading cause of
death in the intensive care units (ICU) or in short time after discharge from
ICU. Developing a rat model of early sepsis involving caecal ligation and
puncture, we undertaken this cardiac MRI study to quantitatively assess myocardial
function and the protective effect of dietary EPA. Our results showed that, in
the exception of the rate of contraction, cardiac functions are less impacted
in the early hyperdynamic phase of sepsis with no/or milder modulation of dietary
EPA.
Introduction
Severe sepsis is a serious syndrome requiring adequate
medical care. It results in multi-organ damage with a significant toxicity:
during the early phase of sepsis, cardiac mechanical activity is increased, but
it progressively declines until cardiac failure. In the Western societies, the
consumption of omega6 (w6)
polyunsaturated fatty acids (PUFA) is too high whereas that of omega3 (w3) PUFA is too low. Yet the consequences of sepsis
could be altered by dietary PUFA which modulate the inflammatory process. The
aim of this study was to determine the effects of dietary eicosapentaenoic acid
(EPA or C20:5 w3) on the
adverse cardiac consequences of sepsis.Materials
Female Wistar rats (n = 32) were fed with a diet
deficient in w3 PUFA (n=16) or with a regime enriched with EPA
(n=16) (187 mg/day) for 14 days. Each group was then submitted (n=8) or not to
sepsis by caecal ligation and puncture (n=8). 48h after the surgical
intervention, the animals were anaesthetized with isofurane for cardiac MR
imaging.Methods
High resolution cine MR imaging was carried out at
11.7T (500MHz) with a 72-mm inner diameter volume coil. Ten to 12 contiguous
1-mm slices were acquired to cover the heart from the base to the apex using short-axis
left ventricular (LV) bright blood cine imaging protocol based on the navigator
self-gated FLASH sequence (repetition time (TR) / echo time (TE) 6/2.5 ms, flip
angle (FA) 8 degrees, field of view (FOV) 5x5 cm, matrix 256x256, slice
thickness 1 mm, oversampling 400). 16 movie frames were reconstructed per slice.
After imaging session, rats were euthanized and the heart removed for analysis
of mitochondrial function.
Image analysis was
performed using software Segment [1]. Semi-automatic
segmentation of the LV was performed as described in [2] to obtain morphological
and functional parameters, e.g., end diastolic volume (EDV), end systolic
volume (ESV), ejection fraction (EF), heart rate (HR) and cardiac output (CO), along
with the contraction and relaxation rates, which were derived from the time
evolution of EDV.Results
Figure 1 show an example of segmentation results
allowing the determination of the rates of contraction and relaxation. Sepsis
did not alter significantly the EDV, ESV, EF, HR and CO. The rate of relaxation
was not modified by the pathologic event either (Figure 2). However, the speed
of contraction tended to be increased (p = 0.085) with the sample size used in
the present study. Dietary EPA had no noticeable influence on the parameters of
cardiac morphology and function. In omega-3 deficient animals, early sepsis
induced an alteration of mitochondrial function in sepsis compared with control
rats: i) drop in mitochondrial respiration (p <0.001); ii) decline in ATP
production (p <0.05); iii) increased release of ROS (p <0.05). This
difference according to the operation undergone is not found in EPA animals.Discussion and conclusion
That sepsis tended to increase the rate of
contraction indicates that the pathology was in its early hyperdynamic phase
with an activation of cardiac function. Since in omega-3 deficient animals,
early sepsis induced drop in mitochondrial respiration (p <0.001) in sepsis
compared to control rats, with no difference observed in EPA animals, the absence
of difference in MRI global cardiac functions may attributed either the
anesthesia or to the early state of sepsis not perceptible in MRI.Acknowledgements
No acknowledgement found.References
[1]
http://segment.heiberg.se
[2] Riegler, J., Cheung,
K. K., Man, Y. F., Cleary, J. O., Price, A. N. and Lythgoe, M. F. (2010), J.
Magn. Reson. Imaging, 32: 869–877