Increased concentration of hypoxanthine in human central cerebrospinal fluid after subarachnoid haemorrhage

Summary The adenine nucleotide metabolites hypoxanthine, xanthine and uric acid were determined by high performance liquid chromatography in cerebrospinal fluid (CSF) from 25 patients with subarachnoid haemorrhage (SAH) and from 26 control subjects. In addition, the haemoglobin and protein levels in the CSF of the patients were determined.In 13 subjects, from which lumbar CSF was collected three, six and nine days after SAH, there was a gradual increase in 8 patients for hypoxanthine and in 3 of the 13 patients for xanthine and uric acid. The mean concentrations were not significantly higher than the controls. In 12 SAH patients, consecutive CSF fractions of 10 ml were collected peroperatively during surgical clipping of aneurysms. The hypoxanthine concentrations increased continously from lumbar to central CSF samples. Hypoxanthine levels were 6.5±1.0 M in lumbar CSF compared to 11.8±2.3 M in central CSF (p<0.001), while xanthine, uric acid, haemoglobin and protein levels were equally distributed. Furthermore, the SAH patients showed about 3 times higher concentrations of central CSF hypoxanthine (p<0.01) and xanthine (p<0.05) while that for uric acid was similar compared to all control subjects. Also, an in vitro study showed that the increased concentrations of the adenine nucleotide metabolites could not be caused by degradation of blood components in the subarachnoid space.It is presumed that the increased central CSF concentrations of hypoxanthine that were demonstrated in patients after SAH could be a sensitive marker for brain tissue ischaemia. However, since there was no correlation between the hypoxanthine levels, clinical condition or cerebral vascular diameter, other factors have to be excluded before ischaemia alone could explain the elevated central hypoxanthine levels in patients without major clinical dysfunction after SAH.This study was supported by grants from Karolinska Institutet, the Swedish National Society against Heart and Chest disease, The Swedish Society of Medical Sciences, Wibergs Foundation, Boehringer Ingelheim and the Swedish Medical Research Council (proj. no. 7485).