S Iwata

118 Delayed Hypoyhermia is Neuroprotective in Moderate, but not Severe, Perinatal Hypoxic-Ischaemic Brain Injury

118 Delayed Hypoyhermia is Neuroprotective in Moderate, but not Severe, Perinatal Hypoxic-Ischaemic Brain Injury

268 Effect of Delayed Whole-Body Cooling to 33°C or 35°C After Transient Cerebral Hypoxia-Ischaemia in the Newborn Piglet

Background: Although delayed cooling after transient perinatal cerebral hypoxia-ischaemia (HI) shows great therapeutic potential in clinical and experimental studies, fundamental questions remain about the optimal cooling temperature and mode of cooling. Aims: To investigate: (i) the effect of delayed cooling at 33°C or 35°C on the evolution of secondary energy failure (SEF) (ii) the relationship between cerebral energy metabolism during SEF and neuronal death.Methods: Piglets were randomised to: (i) HI-normothermic rectal temperature (T) (n=12), (ii) HI-T35°C (n=7), and (iii) HI-T33°C (n=10). Groups (ii) and (iii) were cooled to the target rectal temperature between 2–26 hours following HI. Serial global phosphorous magnetic resonance spectroscopy was used to assess SEF over 48 hrs. At 48 hrs the brain was perfusion fixed and dead neurons assessed in the cortex and deep grey matter. The effect of cooling on SEF (indexed by the nucleotide triphosphate/exchangeable phosphate pool ratio (NTP/EPP)) was assessed using a linear model, which incorporated a random effect for each subject and fixed effects for groups.Results: The cooled groups had significantly higher NTP/EPP than the normothermia group; HI-normothermic mean (95% CI) NTP/EPP was 0.131 (0.118, 0.144); HI-T35°C 0.149 (0.136, 0.162); HI-T33°C 0.149 (0.136, 0.162) (p= 0.032 for HI-T35°C; p=0.044 for HI-T33°C, both vs normothermia). There was no difference in NTP/EPP between HI-T35°C and HI-T33°C (p=0.996). Minimal NTP/EPP 36–48 hours after HI was linearly correlated with neuronal death in cortical and deep grey matter (p<0.05).Conclusions: Compared to normothermia, delayed whole body cooling (33°C and 35°C) ameliorated global SEF. No advantage in global cerebral energy metabolism was detected with cooling to 33°C compared to 35°C, however further work is required to assess whether there is regional variation in the optimal brain temperature for neuroprotection. Minimal NTP/EPP during SEF correlated with neuronal death.Background: Although delayed cooling after transient perinatal cerebral hypoxia-ischaemia (HI) shows great therapeutic potential in clinical and experimental studies, fundamental questions remain about the optimal cooling temperature and mode of cooling. Aims: To investigate: (i) the effect of delayed cooling at 33°C or 35°C on the evolution of secondary energy failure (SEF) (ii) the relationship between cerebral energy metabolism during SEF and neuronal death.Methods: Piglets were randomised to: (i) HI-normothermic rectal temperature (T) (n=12), (ii) HI-T35°C (n=7), and (iii) HI-T33°C (n=10). Groups (ii) and (iii) were cooled to the target rectal temperature between 2–26 hours following HI. Serial global phosphorous magnetic resonance spectroscopy was used to assess SEF over 48 hrs. At 48 hrs the brain was perfusion fixed and dead neurons assessed in the cortex and deep grey matter. The effect of cooling on SEF (indexed by the nucleotide triphosphate/exchangeable phosphate pool ratio (NTP/EPP)) was assessed using a linear model, which incorporated a random effect for each subject and fixed effects for groups.Results: The cooled groups had significantly higher NTP/EPP than the normothermia group; HI-normothermic mean (95% CI) NTP/EPP was 0.131 (0.118, 0.144); HI-T35°C 0.149 (0.136, 0.162); HI-T33°C 0.149 (0.136, 0.162) (p= 0.032 for HI-T35°C; p=0.044 for HI-T33°C, both vs normothermia). There was no difference in NTP/EPP between HI-T35°C and HI-T33°C (p=0.996). Minimal NTP/EPP 36–48 hours after HI was linearly correlated with neuronal death in cortical and deep grey matter (p<0.05).Conclusions: Compared to normothermia, delayed whole body cooling (33°C and 35°C) ameliorated global SEF. No advantage in global cerebral energy metabolism was detected with cooling to 33°C compared to 35°C, however further work is required to assess whether there is regional variation in the optimal brain temperature for neuroprotection. Minimal NTP/EPP during SEF correlated with neuronal death.