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


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 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.


CONCLUSIONS
In this model, an increase in CBF with VP hastens the development of brain edema while increasing ammonia delivery to the brain.
Chung
Chuhan
C
Hepatology Section and Department of Medicine, VA Chicago Health Care System, Lakeside Division and Northwestern University, 400 E. Ontario St., Chicago, IL 60611, USA. a-blei@northwestern.edu
Vaquero
Javier
J
Gottstein
Jeanne
J
Blei
Andres T
AT
D000641:Ammonia / Q000097:blood / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D001929:Brain Edema / Q000139:chemically induced*; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D007427:Intracranial Pressure / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D010100:Oxygen / Q000378:metabolism; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D065092:Antidiuretic Hormone Receptor Antagonists; D014662:Vasoconstrictor Agents; D014867:Water; D014667:Vasopressins; D000641:Ammonia; D010100:Oxygen