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

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.