DISSOCIATED CEREBRAL VASOPARALYSIS IN ACUTE LIVER-FAILURE - A HYPOTHESIS OF GRADUAL CEREBRAL HYPEREMIA

Background/Aims: 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-reactivit y and autoregulation. In patients with fulminant hepatic failure and i n the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cerebral vasoparalysis. Since also CO2-react ivity may then be compromised, it was studied in patients with fulmina nt hepatic failure and rats with thioacetamide-induced liver failure. Methods: In ten patients (median age 32 (range 20-48) years)) and in t en age-matched volunteers, cerebral perfusion was evaluated by transcr anial Doppler assessed mean flow velocity (V-mean) in the middle cereb ral artery during hypo- and hypercapnia. In six rats with liver failur e and in six control rats, cerebral blood flow was measured repeatedly by the intracarotid (133)Xenon injection technique. Results: In the p atients 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 pa tients, 2.2 (1.8-5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p<0.05). In the rat s, PaCO2 was reduced from 39 (37-40) to 30 (29-31) mmHg and then raise d 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), re spectively. In all rats with liver failure CO2-reactivity was abolishe d during hypercapnia, while it was 1.5% mmHg(-1) in the control rats ( p<0.01). Conclusions: The finding that cerebral CO2 reactivity is redu ced in hypercapnia, while it is preserved in hypocapnia, suggests that gradual dilatation of the cerebral resistance vessels develops in ful minant hepatic failure and connects previous morphological studies wit h changes in the regulation of cerebral blood flow, i.e. impaired cere bral autoregulation and blunted CO2-reactivity.