Hypothermia Prolongs the Viability of Ischemic Brain Tissue Due to Neuroprotection Linked to Redistribution of Oxygen in Brain: Positron Emission Tomography Study of the Critical First 6h After Stroke in Pigs

The objective of this study was to verify how 32°C hypothermia reduces the energy metabolism to a level that is commensurate with the prevailing blood flow and hence allows adequate distribution of oxygen to the entire brain tissue using positron emission tomography (PET) in pigs. The hypothermia reduced cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) to 50% of the baseline in 3 and 5 h, respectively. The oxygen extraction fraction (OEF) was significantly elevated to 140% of the baseline in 3h, indicating a reduction of the driving pressure of oxygen delivery in response to the reduced metabolic need, and then gradually returned to the level of the baseline. Cerebral metabolic rate of glucose (CMRglc) decreased to 75% of the baseline at 6 h of hypothermia in response to the lowered metabolism for maintenance of cellular integrity. Cerebral blood volume (CBV) decreased slightly at 3 h and to 72% of the baseline at 6 h of hypothermia. In the stroke model, the hypothermia following reperfusion decreased significantly the volume of infarction even in severe ischemia, whereas the reperfusion alone did not decrease the volume in severe ischemia. Thus, 32°C hypothermia prolongs the therapeutic time window even in severe ischemia by reducing base CMRO2, i.e., the neuroprotection linked to redistribution of oxygen in brain.