The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced following intrauterine inflammation and dopamine infusion

Abstract

Background: Neurovascular coupling leads to an increase in local cerebral blood flow and oxygenation in response to increased neural activity. Reduced cerebral functional responses may predispose to tissue hypoxia when neural activity is increased. Intrauterine inflammation, identified clinically as chorioamnionitis, is a major contributor to the neuropathology arising after preterm birth. The impact of chorioamnionitis on the preterm cerebral functional haemodynamic response is unknown. Previously, we have reported that somatosensory stimulation produces predominantly positive cerebral haemodynamic responses (i.e., increased cerebral oxygenation) in preterm lambs, which are reduced with dopamine treatment. As preterm infants born after chorioamnionitis often suffer from hypotension and are treated with dopamine, we aimed to investigate how chorioamnionitis with and without dopamine treatment affect the cerebral haemodynamic response in preterm lambs.

Methods: At 119 days of gestation, intrauterine inflammation was induced by intra-amniotic injection of lipopolysaccharide (LPS) in pregnant ewes. At 126-7 days of gestation (term is ~147 days), these LPS-exposed lambs were delivered and mechanically ventilated. The cerebral functional response was assessed by near infrared spectroscopy as changes in cerebral oxy- and deoxyhaemoglobin (ΔoxyHb, ΔdeoxyHb), following left median nerve stimulation of 1.8, 4.8 and 7.8 s durations without dopamine; and 4.8 and 7.8 s stimulations with intravenous dopamine infusion.

Results: Stimulation for 1.8, 4.8 and 7.8 s durations led to negative functional responses (decreased ΔoxyHb) in 5 (62.5%), 5 (62.5%) and 4 (50%) of 8 preterm lambs respectively, while other lambs showed positive responses (increased ∆oxyHb). Dopamine infusion increased baseline tissue oxygenation index (TOI), oxyHb and total Hb. In lambs with a positive functional response, dopamine decreased the evoked ΔoxyHb response, increasing the overall incidence of negative cerebral haemodynamic responses.

Conclusions: Somatosensory stimulation produced mostly negative responses with decreased cerebral oxygenation in preterm lambs exposed to intrauterine inflammation, contrasting with our previous findings of predominantly positive responses in non-inflamed, control, preterm lambs. Dopamine increased baseline cerebral oxygenation, but further increased the incidence of negative functional responses. Impaired neurovascular coupling leading to intermittent localised tissue hypoxia may therefore contribute to the neuropathy in infants with chorioamnionitis, with the risk of injury exacerbated with dopamine treatment.

Keywords: Cerebral functional haemodynamic response; Chorioamnionitis; Dopamine; Intrauterine inflammation; Neurovascular coupling; Preterm brain.