Interaction of CO2 and ammonia on cerebral blood flow and O2 consumption in dogs

Z. Brazilay, A. G. Britten, R. C. Koehler

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Studies of acutely induced hyperammonemia and chronic hyperammonemia associated with liver dysfunction suggest that cerebral blood flow (CBF) and O2 consumption (CMR(O)2)) become uncoupled and that CMR(O2) may depend on arterial CO2 tension (Pa(CO)2)). We examined CBF (radiolabeled microspheres) and CMR(O2) during hypercapnia (Pa(CO2) ≃ 74 Torr) and hypocapnia (Pa(CO)2) ≃ 21 Torr) both before and during intravenous ammonium acetate infusion in pentobarbital-anesthetized dogs. Continuous infusion over 120 min produced stable increases of arterial ammonia levels (1,400 μmol/l) by 30 min, whereas CBF, CMR(O2), and O2 extraction (measured at sagittal sinus) remained unchanged when Pa(CO2) was held constant (≃35 Torr). Acute hyperammonemia attenuated the increase in CBF during hypercapnia by 44% and abolished the decrease in CBF during hypocapnia. Regional blood flow to pons and midbrain increased under normocapnic conditions, and midbrain blood flow increased further during hypocapnia. Sodium acetate infusion did not affect CBF responses to CO2. Thus we failed to observe an uncoupling of global CBF and CMR(O2) during normocapnic hyperammonemia, or an interaction of CO2 and ammonia on CMR(O2), although the increased pons and midbrain blood flow may reflect regional effects of ammonia on reticular activating system metabolism. On the basis of the literature, we suggest that the attenuated hypercapnic CBF response may arise from impaired glial regulation of extracellular potassium and bicarbonate concentrations and that lactic acid production, enhanced by combined alkalosis and hyperammonemia, may contribute to the abolistion of hypocapnic vasoconstriction.

Original languageEnglish (US)
Pages (from-to)H500-H507
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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