Arterial pH modulation of regional cerebral blood flow during hyperammonemia in dogs.
Acute hyperammonemia at normal arterial pH causes selective increases in midbrain blood flow in dogs. Unexpectedly, further increases occur with hypocapnia. We investigated whether metabolic acidemia and alkalemia modulate the distribution of ammonium across the blood-brain barrier and if, in turn, midbrain blood flow is effectively modulated. In dogs anesthetized with pentobarbital sodium, hyperammonemia (approximately 940 microM) was produced by a 210-min infusion of ammonium acetate. Concurrent infusion of NaHCO3 increased arterial pH to 7.53 +/- 0.02 (SE), whereas HCl infusion decreased pH to 7.11 +/- 0.01. Normocapnia was maintained. Cerebrospinal fluid [HCO3-] increased 5 mM with alkalemia (one-half of the increase in blood) and was unchanged with acidemia. Thus cerebrospinal fluid [H+]/blood [H+] was greater with alkalemia than acidemia. The corresponding ratio for ammonium was likewise greater with alkalemia (0.70 +/- 0.06) than acidemia (0.44 +/- 0.08). Microsphere-determined blood flow to midbrain more than doubled in the alkalemic group but was unchanged in the acidemic group. No other region along the neuraxis or in cerebrum showed increased blood flow in either hyperammonemic group. Alkalemia without hyperammonemia did not increase midbrain blood flow. Thus metabolic acidemia-alkalemia significantly alters ammonium partitioning into cerebrospinal fluid, and this alteration is sufficiently great to exert a specific physiological effect manifested by changes in midbrain blood flow.
Weigle
C G
CG
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Koehler
R C
RC
Brusilow
S W
SW
Traystman
R J
RJ
D000641:Ammonia / Q000097:blood* / Q000134:cerebrospinal fluid; D000818:Animals; D001784:Blood Gas Analysis; D001921:Brain / Q000098:blood supply / Q000502:physiology; D002536:Cerebral Arteries / Q000502:physiology*; D004285:Dogs; D005260:Female; D005971:Glutamates / Q000097:blood; D018698:Glutamic Acid; D005973:Glutamine / Q000097:blood; D006439:Hemodynamics / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008659:Metabolic Diseases / Q000097:blood; D009994:Osmolar Concentration; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow
D005971:Glutamates; D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia