Delayed whole-body cooling to 33 or 35 degrees C and the development of impaired energy generation consequential to transient cerebral hypoxia-ischemia in the newborn piglet.

OBJECTIVES: Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the "latent phase" may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33 degrees C or 35 degrees C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI. METHODS: Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2) HI-Trectal 35 degrees C (HI-35; n = 7), and (3) HI-Trectal 33 degrees C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed. RESULTS: Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming. CONCLUSIONS: Whole-body hypothermia for 24 hours at either 35 or 33 degrees C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33 degrees C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase.

Simultaneous NIR-EPR spectroscopy of rat brain oxygenation.

Changes in cerebral oxygenation were simultaneously monitored by electric paramagnetic resonance (EPR) oximetry and near-infrared spectroscopy (NIRS). The tissue oxygen tension (t-pO2) was measured with an L-band (1.2 GHz) EPR spectrometer with an external loop resonator and the concentration of oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] were measured with a full-spectral NIRS system. Mean cerebral hemoglobin saturation (SmcO2) was calculated from the absolute [HbO2] and [Hb]. Six adult male rats were implanted with lithium phthalocyanine (LiPc) crystals into the left cerebral cortex. The change in oxygenation of the brain was induced by altering the inspired oxygen fraction (FiO2) in air from 0.30 at baseline to 0.0, 0.05, 0.10, and 0.15 for 1, 2, 5, and 5 minutes, respectively, followed by reoxygenation with an FiO2 = 0.30. Although both t-pO2 and SmcO2 values showed a decrease during reduced FiO2 followed by recovery on reoxygenation, it was found that SmcO2 recovered more rapidly than t-PO2 during the recovery phase. The recovery of t-pO2 is not only related to blood oxygenation, but also to delivery, consumption, and diffusion of oxygen into the tissue from the vascular system. Further studies will be required to determine the exact mechanisms for the delay between the recovery of SmcO2 and t-pO2.