Abstract
RATIONALE: Neonatal sepsis remains a major problem, partly due to their consequences on cardiorespiratory control. The latter manifest as severe cardiorespiratory events and cause substantial morbidity and mortality, especially in preterm infants. The link between neonatal sepsis, inflammation and altered cardiac and respiratory activity remains poorly understood. Our research program aims to further characterize this link in newborn lambs, who are closer to the human newborn than the murine models previously studied.METHODS: Two six-hour polysomnography recordings were performed on two consecutive days in eight full-term newborn lambs. During the first recording, an IV saline injection (= control) was given, whereas the second recording was performed after an IV injection of 2.5 μg/kg of E. coli LPS 0127:B8. Body temperature, arterial blood gases, states of alertness, locomotor activity, respiratory and heart rates, arterial blood pressure, apneas and cardiac decelerations were measured. RESULTS: LPS injection induced a biphasic increase in body temperature [max To = +1.3oC at 30 and 180 min] and decreased locomotor activity [38.7 (35.4, 54) vs. 93.8 (73, 128.1) m, median (Q1,Q3), p = 0.03] and active wakefulness [21 (17, 23) vs. 28 (19, 31) % p= 0.01] vs. control condition. Meanwhile, quiet wakefulness [51 (47, 53) vs. 42 (37, 47) %, p = 0.03], number of cardiac decelerations [37 (33, 89) vs. 19 (13, 34), p = 0.05], heart rate [245 (229, 261) vs. 180 (172, 183) .min-1, p = 0.005] and respiratory rate [61 (59, 63) vs. 49 (47, 52) .min-1, p = 0.0005] were increased, while total apnea duration [35.7 (18.2, 61.6) vs. 88.5 (42.7, 133.7) s, p = 0.04] was decreased. CONCLUSION: LPS injection mimics a bacterial sepsis in newborn lambs with multiple consequences, including cardiorespiratory alterations. Ongoing studies in the same lambs will provide further results on alterations of heart and respiratory rate variabilities, as well as on brainstem cardiorespiratory center inflammation. The present results will pave the way for similar studies in preterm lambs.