Abstract
Background: Following transient hypoxia-ischaemia (HI) a latent phase or therapeutic window exists when intervention, such as hypothermia, may ameliorate the secondary energy failure (SEF), which is associated with neuronal death. In clinical practice, there is an unavoidable lag between the recognition of HI and the opportunity to initiate neuroprotective interventions; the precise duration of the therapeutic window is unknown.
Aims: To assess the relationships between the severity of transient HI, the duration of the latent phase and the regional SEF quantified by the brain-water apparent diffusion coefficient (ADC).
Methods: Eighteen newborn piglets were subjected to transient HI (bilateral carotid occlusion and FiO2 12–16%) for up to 45min giving a range of insult severity within the bore of a 7 Tesla magnetic resonance (MR) scanner. During HI phosphorus MR spectroscopy was used to assess insult severity, which was quantified by the duration and magnitude of depletion of nucleotide triphosphate (NTP) relative to the exchangeable high-energy phosphate pool (EPP). Grey matter ADC was serially measured to provide an index of the severity of SEF. The 99% confidence interval (CI) for NTP/EPP prior to HI was defined. The duration of the latent phase was the period following HI between NTP/EPP recovering to within CI and NTP/EPP falling below CI again indicating the development of SEF.
Results: The latent phase duration correlated negatively with insult severity (r=-0.625, p<0.05). During SEF cortical ADC correlated linearly with the duration of the latent phase (r=0.852, p<0.01 at 12 hours and r=0.89, p<0.05 at 24 hours).
Conclusion: The more severe the acute HI insult, the shorter the latent phase. A shorter latent phase led to a greater extent of subsequent brain SEF. Newborn infants who have suffered severe HI may be less likely to respond to neuroprotective treatments because of the shorter therapeutic window.
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Iwata, O., De Vita, E., Bainbridge, A. et al. 180 Cerebral Energy Depletion During Hypoxia-Ischaemia, Therapeutic Window, and Regional Severity of Secondary Energy Failure in Newborn Piglets. Pediatr Res 58, 385 (2005). https://doi.org/10.1203/00006450-200508000-00209
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DOI: https://doi.org/10.1203/00006450-200508000-00209