PRESERVATION OF CEREBRAL BLOOD-FLOW RESPONSES TO HYPOXIA AND ARTERIAL-PRESSURE ALTERATIONS IN HYPERAMMONEMIC RATS

Acute hyperammonemia causes cerebral edema, elevated intracranial pres sure and loss of cerebral blood flow (CBF) responsivity to CO2. Inhibi tion of glutamine synthetase prevents these abnormalities. If the loss of CO2 responsivity is secondary to the mechanical effects of edema, one would anticipate loss of responsivity to other physiological stimu li, such as hypoxia and changes in mean arterial blood pressure (MABP) . To test this possibility, pentobarbital-anesthetized rats were subje cted to either hypoxic hypoxia (PaO2 approximate to 30 mm Hg), hemorrh agic hypotension (MABP approximate to 70 and 50 mm Hg), or phenylephri ne-induced hypertension (MABP approximate to 125 and 145 mm Hg). CBF w as measured with radiolabeled microsphere. Experimental groups receive d intravenous ammonium acetate (approximate to 50 mu mol min(-1) kg(-1 )) for 6 h to increase plasma ammonia to 50-600 mu M. Control groups r eceived sodium acetate plus HCl to prevent metabolic alkalosis. The in crease in CBF during 10 min of hypoxia after 6 h of ammonium acetate i nfusion (84 +/- 19 to 259 +/- 52 ml min(-1) 100 g(-1)) was similar to that after sodium acetate infusion (105 +/- 20 to 265 +/- 76 mi min(-1 ) 100 g(-1)). Cortical glutamine concentration was elevated equivalent ly in hyperammonemic rats subjected to normoxia only or to 10 min of h ypoxia. With severe hypotension, CBF was unchanged in both the ammoniu m (80 +/- 20 to 76 +/- 24 ml min(-1) 100 g(-1)) and the sodium (80 +/- 14 to 73 +/- 16 mi min(-1) 100 g(-1)) acetate groups, With moderate h ypertension, CBF was unchanged. With the most severe hypertension, sig nificant increases in CBF occurred in both groups, but there was no di fference between groups. We conclude that hypoxic and autoregulatory r esponses are intact during acute hyperammonemia. The previously observ ed loss of CO2 responsivity is not the result of a generalized vasopar alysis to al physiological stimuli.