EXTRACELLULAR ISCHEMIA MARKERS IN REPEATED GLOBAL-ISCHEMIA AND SECONDARY HYPOXEMIA MONITORED BY MICRODIALYSIS IN RAT-BRAIN

The aim of this study was to explore the usefulness of extracellular m arkers of cerebral ischaemia. Cortical microdialysate concentrations o f the energy related metabolites lactate, pyruvate, glucose, adenosine , inosine, hypoxanthine and xanthine, were measured in rats subjected to repeated transient ischaemia. The animals were subjected to one or two 10-min periods of global ischaemia produced by induced intracrania l hypertension, with a 2 h period of reperfusion after each insult. In addition, the effect of superimposed secondary hypoxaemia and hypoten sion was studied. In general, there was a good agreement between the e xtracellular markers and known intracellular energy disturbances under similar conditions, including marked transient increases of lactate, lactate/pyruvate ratio, inosine and hypoxanthine. Several new observat ions were made: (1) glucose appeared to be a useful marker of severe i schaemia and recirculation? (2) a marked post-ischaemic xanthine forma tion was observed implicating a substantial loss of salvageable hypoxa nthine as well as increased production of superoxide radicals, (3) a b lunted purine response was noted after the second insult, reflecting a reduced intracellular adenine nucleotide pool, and (4) a different pa ttern of ischaemia markers was observed during secondary hypoxia as co mpared to hypoxia with hypotension. In conclusion, extracellular lacta te, pyruvate, glucose, adenosine, inosine hypoxanthine and xanthine al l seem valuable as ischaemia markers. The results support the usefulne ss of intracerebral microdialysis for monitoring of energy metabolic d isturbances caused by cerebral ischaemia/hypoxia. The pattern of extra cellular ischaemia markers may help differentiate between various caus es of energy perturbations, such as different degrees of ischaemia and hypoxia.