CEREBRAL BLOOD-FLOW AUTOREGULATION IS ABSENT IN RATS WITH THIOACETAMIDE-INDUCED HEPATIC-FAILURE

Cerebral blood flow normally remains constant within a wide range of mean arterial blood pressure values. In fulminant hepatic failure, however, it is not known whether autoregulation of cerebral blood Row is maintained. In the present study, cerebral blood flow autoregulation was investigated in rats 3 days after induction of fulminant hepatic failure. Wistar rats were given intraperitoneal thioacetamide or saline injections. The mean arterial blood pressure was varied by means of norepinephrine infusion or venesection, respectively. As mean arterial blood pressure declined, repeated cerebral blood flow measurements were performed by the intracarotid (113)Xenon injection method. The relation between mean arterial blood pressure and cerebral blood flow was examined by statistical regression analysis, and the lower limit of autoregulation was determined in each rat. Cerebral blood flow baseline values were unaltered in liver failure compared to the control group (73 (36-92) vs. 79 (57-87) ml.100 g(-1).min(-1), median and range). Baseline mean arterial blood pressure was also similar in the two groups (90 (75-113) vs. 95 (70-112)). Mean arterial blood pressure varied between 40 (35-50) and 110 (90-135) mmHg in the control rats and between 50 (45-68) and 110 (95-126) mmHg in the rats with liver failure. A lower limit of autoregulation was identified in all control rats at a mean arterial blood pressure of 67 (55-78) mmHg. Below this limit, cerebral blood flow declined in parallel with mean arterial blood pressure. None of the rats with liver failure exhibited autoregulation, and cerebral blood flow changed in parallel with mean arterial blood pressure. In conclusion, cerebral blood flow autoregulation seems to be absent in rats with thioacetamide-induced hepatic failure. Cerebral blood flow decreases in parallel with blood pressure and, during hypotensive episodes, the decrease in brain perfusion may be too low to maintain sufficient brain metabolism. (C) Journal of Hepatology.