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 (CMRO2) become uncoupled and that CMRo2 may depend on arterial CO2 tension (PaCO2). We examined CBF (radiolabeled microspheres) and CMRO2 during hypercapnia (PaCO2 congruent to 74 Torr) and hypocapnia (PaCO2 congruent to 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 mumol/l) by 30 min, whereas CBF, CMRO2, and O2 extraction (measured at sagittal sinus) remained unchanged when PaCO2 was held constant (congruent to 35 Torr). Acute hyperammonemia attenuated the increase in CBF during hypercapnia by 44% and abolished the decrease in CBF during hypercapnia. 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 CMRO2 during normocapnic hyperammonemia, or an interaction of CO2 and ammonia on CMRO2, 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 abolition of hypocapnic vasoconstriction.
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010313:Partial Pressure
D000085:Acetates; D002245:Carbon Dioxide; D000641:Ammonia; D019342:Acetic Acid; C018824:ammonium acetate