Ischaemic Thresholds and Development of Ischaemia
In experiments with reversible middle cerebral artery occlusion (MCAO) in cats and monkeys, reversible paralysis occurs when CBF is reduced to 23 ml/100 g/min and irreversible paralysis supervenes when CBF is permanently reduced to about 17–18 ml (Heiss et al. 1976, Jones et al. 1981). In studies of gerbils subjected to acute cerebral ischaemia by carotid ligation, a CBF threshold of CBF at 20 m1/100 g/min has been defined; below this threshold MR spectroscopy shows metabolic failure with phosphocreatine and ATP decline, combined with lactate accumulation and a fall in intracellular pH indication that failure of synaptic function is a direct consequence of energy failure (Crockard et al. 1987). In experiments with primates subjected to MCAO, pH in the extracellular space remains stable until CBF levels of 20 ml/100 g/min; below this value pH fell rapidly (Harris et al. 1987) and an increase in brain water was observed (Symon et al. 1979). If CBF falls to about 10 ml/100 g/min, further cytotoxic oedema occurs as a result of sodium passage into the cells.