Chung, C., Vaquero, J., Gottstein, J. & Blei, A. T. Vasopressin accelerates experimental ammonia-induced brain edema in rats after portacaval anastomosis. J. Hepatol. 39, 193-199
Hepatology Section and Department of Medicine, VA Chicago Health Care System, Lakeside Division and Northwestern University, 400 E. Ontario St., Chicago, IL 60611, USA. Journal of Hepatology
(Impact Factor: 11.34).
08/2003; 39(2):193-9. DOI: 10.1016/S0168-8278(03)00185-5
Cerebral hyperemia is an important contributor to the development of brain edema in fulminant hepatic failure. Rats receiving an ammonia infusion after portacaval anastomosis (PCA) demonstrate a rise in cerebral blood flow (CBF) with brain edema at 180 min. Vasopressin (VP), a systemic vasoconstrictor which in the rat dilates cerebral vessels through V(2) receptors, was used to ascertain the effects of increasing CBF.
Changes in CBF were measured with Laser Doppler flowmetry (LDF). Absolute CBF was measured with radioactive microspheres to calculate oxygen and ammonia uptake.
Compared to the NH(3)+Vehicle group, VP+NH(3) infusion accelerated the rise in CBF (117+/-21 vs. -6+/-12%, P<0.01), and the development of brain edema (81.09+/-0.17 vs. 80.29+/-0.06%, P<0.01). Radioactive microspheres confirmed these results (254+/-44 vs. 106+/-9.5 ml/min/100 g, P<0.01). Oxygen uptake was similar. Ammonia uptake was more than twofold higher in the VP+NH(3) group. A V(1) antagonist negated the higher mean arterial pressure (MAP) that occurs with VP but cerebral hyperemia still occurred. A V(2) antagonist resulted in similar systemic pressures, CBF and brain water compared to the VP+NH(3) group.
In this model, an increase in CBF with VP hastens the development of brain edema while increasing ammonia delivery to the brain.
Available from: Javier Vaquero
- "Both cerebral hyperemia and loss of autoregulation are corrected by hypothermia. In the portacaval-shunted rat receiving an ammonia infusion, where CBF and brain edema are intimately connected  , the reduction of brain edema by hypothermia was accompanied by the prevention of cerebral hyperemia . Similarly, studies in patients with ALF and refractory intracranial hypertension showed that the rapid reduction of ICP after starting mild hypothermia was paralleled by decreases of CBF and cerebral uptake of ammonia  . "
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ABSTRACT: Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.
Available from: Debbie L Shawcross
Available from: Nanna Macaulay
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