Hirata T, Koehler R C, Brusilow S W, Traystman R J
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
J Cereb Blood Flow Metab. 1995 Sep;15(5):835-44. doi: 10.1038/jcbfm.1995.104.
Acute hyperammonemia causes cerebral edema, elevated intracranial pressure and loss of cerebral blood flow (CBF) responsivity to CO2. Inhibition 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 stimuli, such as hypoxia and changes in mean arterial blood pressure (MABP). To test this possibility, pentobarbital-anesthetized rats were subjected to either hypoxic hypoxia (PaO2 approximately 30 mm Hg), hemorrhagic hypotension (MABP approximately 70 and 50 mm Hg), or phenylephrine-induced hypertension (MABP approximately 125 and 145 mm Hg). CBF was measured with radiolabeled microspheres. Experimental groups received intravenous ammonium acetate (approximately 50 mumol min-1 kg-1) for 6 h to increase plasma ammonia to 500-600 microM. Control groups received sodium acetate plus HCl to prevent metabolic alkalosis. The increase in CBF during 10 min of hypoxia after 6 h of ammonium acetate infusion (84 +/- 19 to 259 +/- 52 ml min-1 100 g-1) was similar to that after sodium acetate infusion (105 +/- 20 to 265 +/- 76 ml min-1 100 g-1). Cortical glutamine concentration was elevated equivalently in hyperammonemic rats subjected to normoxia only or to 10 min of hypoxia. With severe hypotension, CBF was unchanged in both the ammonium (80 +/- 20 to 76 +/- 24 ml min-1 100 g-1) and the sodium (80 +/- 14 to 73 +/- 16 ml min-1 100 g-1) acetate groups. With moderate hypertension, CBF was unchanged. With the most severe hypertension, significant increases in CBF occurred in both groups, but there was no difference between groups. We conclude that hypoxic and autoregulatory responses are intact during acute hyperammonemia. The previously observed loss of CO2 responsivity is not the result of a generalized vasoparalysis to all physiological stimuli.
急性高氨血症可导致脑水肿、颅内压升高以及脑血流量（CBF）对二氧化碳反应性丧失。抑制谷氨酰胺合成酶可预防这些异常情况。如果二氧化碳反应性丧失是由水肿的机械作用继发引起的，那么可以预期对其他生理刺激的反应性也会丧失，比如缺氧和平均动脉血压（MABP）变化。为了验证这种可能性，对戊巴比妥麻醉的大鼠进行低氧性缺氧（动脉血氧分压约30 mmHg）、出血性低血压（MABP约70和50 mmHg）或去氧肾上腺素诱导的高血压（MABP约125和145 mmHg）处理。用放射性微球测量CBF。实验组静脉输注醋酸铵（约50 μmol·min⁻¹·kg⁻¹）6小时，以使血浆氨水平升至500 - 600 μM。对照组输注醋酸钠加盐酸以预防代谢性碱中毒。醋酸铵输注6小时后，在10分钟缺氧期间CBF的增加（从84±19至259±52 ml·min⁻¹·100 g⁻¹）与输注醋酸钠后相似（从105±20至265±76 ml·min⁻¹·100 g⁻¹）。仅处于常氧状态或经历10分钟缺氧的高氨血症大鼠，其皮质谷氨酰胺浓度升高程度相当。在严重低血压时，醋酸铵组（从80±20至76±24 ml·min⁻¹·100 g⁻¹）和醋酸钠组（从80±14至73±16 ml·min⁻¹·100 g⁻¹）的CBF均未改变。在中度高血压时，CBF也未改变。在最严重高血压时，两组的CBF均显著增加，但两组之间无差异。我们得出结论，在急性高氨血症期间，缺氧反应和自身调节反应是完整的。先前观察到的二氧化碳反应性丧失并非对所有生理刺激的全身性血管麻痹的结果。
