Studies of experimental cerebral ischaemia using nuclear magnetic resonance and hydrogen clearance.

The object of this research has been to examine various aspects of brain metabolism and physiology during and after ischaemia, which was produced by carotid artery occlusion. Firstly, the relationship between energy metabolism (measured by 31P and 1H NMR spectroscopy) and CBF (using hydrogen clearance) during ischaemia was examined. A remotely (manually) controlled snare system to occlude the carotid arteries and a computerised rapid method of calculating CBF gave a greater degree of control over the blood flow than was previously possible. Small changes in energy metabolites were seen at flows between 20 and 30 ml 100 g-1 min-1 with a marked deterioration of energy metabolism at flows below 20 ml 100 g-1 min-1. The potential of this model for testing therapeutic agents was explored using hypothermia. Specific gravity microgravimetry has been used to measure the development of oedema after ischaemia, and this has been correlated with the time course of recovery of phosphorus-containing metabolites, intracellular pH (pHi) and lactate. Phosphorus metabolites returned to pre-ischaemic levels by 12 minutes, pHi by 20 minutes, and lactate by 50 minutes. There was a lag of about 10 minutes before lactate began to be cleared from the brain. Oedema was still resolving at 3 hours of reperfusion. Magnetic resonance imaging was used to examine changes in the brain after various periods of ischaemia. This showed that the extent of injury to the brain, as judged by the appearance of lesions on reperfusion, was dependent on the duration of ischaemia. Changes in the images occurred between 2.5 to 5 minutes after carotid artery occlusion if cerebral blood flow was reduced below 15 to 20 ml 100 g-1 min-1 which is the threshold for failure of the cellular ionic pumps. To examine the hypoxic component of ischaemia separately, a hypoxia model (without ischaemia) was developed, which demonstrated that energy metabolites in the brain are very resistant to hypoxia. Half the animals in the study showed an increase in lactate prior to any change in phosphorus metabolites, which suggests that 1H NMR may be more sensitive than 31P NMR at detecting hypoxic/ischaemic changes in the brain