title: Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure.
abstract: OBJECTIVE
  The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively).
  
  
  METHODS
  In 17 patients (aged 18-60 years) with acute liver failure and severe hyperammonemia (182 ± 36 μM (mean ± SD)), cerebral microdialysis was performed, and ICP and CPP were monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and pyruvate were measured.
  
  
  RESULTS
  The hypoxanthine concentration was 23.0 ± 12 μM in early samples and 11.7 ± 6.8 μM in late samples (normal level ~2.0 μM). The inosine concentration was 7.2 ± 7.1 μM and 2.8 ± 1.6 μM, and the LP ratio was 55.8 ± 21.6 and 45.6 ± 20.8, respectively (normal level ~18). Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP, nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients without (n=8).
  
  
  CONCLUSIONS
  This study shows that the high cerebral LP ratio correlates to the hypoxanthine level in patients with acute liver failure. However, these metabolic alterations were not related to the development of intracranial hypertension.
authors.affiliation: Department of Hepatology, Rigshospitalet, University Hospital of Copenhagen, Denmark. peter.nissen.bjerring@rh.regionh.dk
authors.forename: Peter Nissen
authors.initials: PN
authors.lastname: Bjerring
authors.forename: John
authors.initials: J
authors.lastname: Hauerberg
authors.forename: Linda
authors.initials: L
authors.lastname: Jørgensen
authors.forename: Hans-Jørgen
authors.initials: HJ
authors.lastname: Frederiksen
authors.forename: Flemming
authors.initials: F
authors.lastname: Tofteng
authors.forename: Bent Adel
authors.initials: BA
authors.lastname: Hansen
authors.forename: Fin Stolze
authors.initials: FS
authors.lastname: Larsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000150:complications; D019271:Hypoxanthine / Q000378:metabolism*; D007288:Inosine / Q000378:metabolism; D019586:Intracranial Hypertension / Q000209:etiology; D007427:Intracranial Pressure; D019344:Lactic Acid / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D019289:Pyruvic Acid / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019271:Hypoxanthine; D019344:Lactic Acid; D007288:Inosine; D019289:Pyruvic Acid