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A7238 - Cardiorespiratory Alterations in an Ovine Neonatal Model of Bacterial Infection
Author Block: S. Nault1, A. Levasseur1, C. Nadeau1, N. Samson1, P. Pladys2, J. Praud1; 1University of Sherbrooke, Sherbrooke, QC, Canada, 2University of Rennes 1, Rennes, France.
RATIONALE: Postnatal infections remain a major problem, partly due to their consequences on cardiorespiratory control. The latter manifests as severe cardiorespiratory events in premature newborns with late-onset sepsis as well as in young infants with community-acquired infections. While studies in rodents support an inhibitory role for PGE2 on respiratory centers (Hofstetter AO, 2007), the link between infection, inflammation and alterations in cardiorespiratory control remains ill-understood. We hypothesize that newborn ovine models, including full-term and preterm lambs, can help gaining further insight into the mechanisms involved in that link, paving the way for better care and detection of infected newborns. As a first step in this research program, the aim of the present study was to describe the clinical responses of full-term newborn lambs to lipopolysaccharides (LPS) IV injection, as a model of systemic inflammation due to neonatal bacterial infection. METHODS: Two six-hours polysomnography recordings were performed on two consecutive days in seven full-term, newborn lambs aged 3-4 days. During the first recording (control), an IV saline injection was given, whereas the second recording was performed after IV injection of 2.5 μg/kg of E. coli LPS 0127:B8, a Toll-like receptor-4 agonist. General condition and cardiorespiratory variables, including respiratory and heart rates, systemic arterial pressure, apneas, cardiac decelerations and O2 desaturations were assessed. RESULTS: Compared to control, LPS IV injection induced a generalized hypotonia and increased sleepiness, as well as a significant increase in body temperature (double-peak in 4/7 lambs). Simultaneously, a significant increase in respiratory rate (p = 0.02) and heart rate (p = 0.02) was observed vs control. While the number of cardiac decelerations was increased after LPS (p = 0.04), no significant difference was observed for apneas. Finally, no alterations in arterial pressure or SaO2 were observed after IV LPS.
CONCLUSION: The present data confirm that LPS IV injection induces cardiorespiratory activity alterations in full-term newborn lambs. Assessment of heart rate and respiratory rate variability, as well as responses to vagal stimulation, are now being performed. Further studies will have to assess the inflammatory mechanisms at the level of the cardiorespiratory centers. Finally, studies in preterm lambs will allow to determine the impact of prematurity on the effects of LPS on cardiorespiratory centers. FUNDING: Supported by the Canadian Institutes of Health Research and the Canada Research Chair in Neonatal Respiratory Physiology.