Cerebral blood flow autoregulation in experimental liver failure.
Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood/toxins into the systemic circulation thus mimicking intrahepatic shunting in ALF, PCA+NH(3) provided information about the additional effects of hyperammonemia Rats were intubated and sedated with pentobarbital. We measured CBF with laser Doppler, intracranial pressure (ICP) was measured in the fossa posterior and registered with a pressure transducer, brain water was measured using the wet-to-dry method, and cerebral glutamine/glutamate was measured enzymatically. The CBF autoregulatory index in both the GlN and PHx90 groups differed significantly from the control group. Conversely, CBF autoregulation was intact in the PCA and PCA+NH(3) groups despite high arterial ammonia, high cerebral glutamine concentration, and increased CBF and ICP. Increased water content of the brainstem or cerebellum was not associated with defective CBF autoregulation. In conclusion, impairment of CBF autoregulation is not caused by brain edema/high ICP. Nor does portacaval shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis and reduced liver mass are associated with loss of CBF autoregulation.
Department of Hepatology, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark. thomasdethloff@yahoo.dk
Thomas J
TJ
Dethloff
Gitte Moos
GM
Knudsen
Fin Stolze
FS
Larsen
D000641:Ammonia / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D019586:Intracranial Hypertension / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D017114:Liver Failure, Acute / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008955:Models, Cardiovascular; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D014867:Water / Q000378:metabolism
D014867:Water; D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia