title: Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia.
abstract: OBJECTIVE
  Normally, cerebral blood flow responds to changes in the arterial carbon dioxide tension (PaCO2) but not to changes in mean arterial pressure, commonly referred to as the cerebral CO2-reactivity and autoregulation. In patients with fulminant hepatic failure and in the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cerebral vasoparalysis. Since also CO2-reactivity may then be compromised, it was studied in patients with fulminant hepatic failure and rats with thioacetamide-induced liver failure.
  
  
  METHODS
  In ten patients (median age 32 (range 20-48) years)) and in ten age-matched volunteers, cerebral perfusion was elevated by transcranial Doppler assessed mean flow velocity (V(mean)) in the middle cerebral artery during hypo- and hyper-capnia. In six rats with liver failure and in six control rats, cerebral blood flow was measured repeatedly by the intracarotid 133 Xenon injection technique.
  
  
  RESULTS
  In the patients and volunteers, PaCO2 was lowered from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (34-48) mmHg by hypercapnia or 5% CO2 inhalation. During hypocapnia, the CO2-reactivity did not differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. 3.0 (1.7-5.0)% mmHg(-1), while it was reduced during hypercapnia in the patients, 2.2 (1.8-5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p < 0.05). In the rats, PaCO2 was reduced from 39 (37-40) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During hypocapnia, CO2-reactivity was similar in rats with liver failure and in control rats, 2.3 vs 2.7% mmhg(21), respectively. In all rats with liver failure CO2-reactivity was abolished during hypercapnia, while it was 1.5% mmHg(-1) in the control rats (p < 0.01).
  
  
  CONCLUSIONS
  The finding that cerebral CO2 reactivity is reduced in hypercapnia, while it is preserved in hypocapnia, suggests that gradual dilation of the cerebral resistance vessels develops in fulminant hepatic failure and connects previous morphological studies with changes in the regulation of cerebral blood flow, i.e. impaired cerebral autoregulation and blunted CO2-reactivity.
authors.affiliation: Department of Hepatology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: F S
authors.initials: FS
authors.lastname: Larsen
authors.forename: B
authors.initials: B
authors.lastname: Adel Hansen
authors.forename: F
authors.initials: F
authors.lastname: Pott
authors.forename: E
authors.initials: E
authors.lastname: Ejlersen
authors.forename: N H
authors.initials: NH
authors.lastname: Secher
authors.forename: O B
authors.initials: OB
authors.lastname: Paulson
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000818:Animals; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000209:etiology; D005260:Female; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000150:complications*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D006940:Hyperemia / Q000209:etiology; D016857:Hypocapnia / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide
chemical_list: D013853:Thioacetamide