Positive end expiratory pressure (PEEP) improves oxygenation in mechanically ventilated preterm neonates by preventing lung collapse. However, high PEEP may alter cerebral blood flow secondary to the increased intrathoracic pressure, predisposing to brain injury. The precise effects of high PEEP on cerebral haemodynamics in the preterm brain is unknown. We aimed to assess the effect of PEEP on microvessels in the preterm brain using synchrotron radiation (SR) microangiography which, enables in vivo real-time high-resolution imaging of the cerebral vasculature. Preterm lambs (0.8 gestation, n=4) were delivered via caesarean section, anaesthetised and ventilated. SR microangiography of the right cerebral hemisphere was performed with iodine contrast administered into the right carotid artery, during PEEP ventilation of 5 and 10 cmH2O respectively. Carotid blood flow was measured using an ultrasonic flow probe placed around the left carotid artery. An increase of PEEP from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm), but decreased diameter of larger cerebral vessels (>500 µm) in all 4 lambs. Additionally, the higher PEEP increased the cerebral contrast transit time in 3 of the 4 lambs. Carotid blood flow increased in 2 lambs which, also had increased carbon dioxide levels during PEEP 10. Our results suggest that PEEP of 10 cmH2O alters the preterm cerebral haemodynamics, with prolonged cerebral blood flow transit and engorgement of small cerebral microvessels likely due to the increased intrathoracic pressure. These microvascular changes are generally not reflected in global assessment of cerebral blood flow or oxygenation.

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Neurovascular coupling has been well-defined in the adult brain, but variable and inconsistent responses have been observed in the neonatal brain. The mechanisms that underlie functional haemodynamic responses in the developing brain are unknown. Synchrotron radiation (SR) microangiography enables in vivo high-resolution imaging of the cerebral vasculature. We exploited SR microangiography to investigate the microvascular changes underlying the cerebral haemodynamic response in preterm (n = 7) and 7–10-day old term lambs (n = 4), following median nerve stimulation of 1.8, 4.8 and 7.8 sec durations. Increasing durations of somatosensory stimulation significantly increased the number of cortical microvessels of ≤200 µm diameter in 7–10-day old term lambs (p < 0.05) but not preterm lambs where, in contrast, stimulation increased the diameter of cerebral microvessels with a baseline diameter of ≤200 µm. Preterm lambs demonstrated positive functional responses with increased oxyhaemoglobin measured by near infrared spectroscopy, while 7–10-day old term lambs demonstrated both positive and negative responses. Our findings suggest the vascular mechanisms underlying the functional haemodynamic response differ between the preterm and 7–10-day old term brain. The preterm brain depends on vasodilatation of microvessels without recruitment of additional vessels, suggesting a limited capacity to mount higher cerebral haemodynamic responses when faced with prolonged or stronger neural stimulation.