Vasopressin accelerates experimental ammonia-induced brain edema in rats after portacaval anastomosis

Background/Aims: 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 V2 receptors, was used to ascertain the effects of increasing CBF. Methods: Changes in CBF were measured with Laser Doppler flowmetry (LDF). Absolute CBF was measured with radioactive microspheres to calculate oxygen and ammonia uptake. Results: Compared to the NH3+Vehicle group, VP+NH3 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+NH3 group. A V1 antagonist negated the higher mean arterial pressure (MAP) that occurs with VP but cerebral hyperemia still occurred. A V2 antagonist resulted in similar systemic pressures, CBF and brain water compared to the VP+NH3 group. Conclusions: In this model, an increase in CBF with VP hastens the development of brain edema while increasing ammonia delivery to the brain.