title: Activation-induced resetting of cerebral metabolism and flow is abolished by beta-adrenergic blockade with propranolol.
abstract: OBJECTIVE
  It has previously been shown that activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR(glc)) in excess of cerebral oxygen uptake (CMRO(2)). Our purpose was to investigate the influence of beta-adrenergic blockade with propranolol on the activation-induced uncoupling of cerebral glucose and oxygen metabolism.
  
  
  METHODS
  Using awake rats, we determined the cerebral arteriovenous differences of oxygen [(a-v)(O2)], glucose [(a-v)(glc)], and lactate [(a-v)(lac)] both under baseline conditions and during activation. The molar ratio between CMRO(2) and CMR(glc), the oxygen-glucose index (OGI), was calculated.
  
  
  RESULTS
  Without beta-adrenergic blockade, activation decreased the (a-v)(O2) but not the (a-v)(glc), reducing the OGI from 6.1 during baseline conditions to 4.0 under activation (P<0.01). The (a-v)(O2) decreased, indicating that the ratio CBF/CMRO(2) had increased. Under baseline conditions, a slight flux of lactate from the brain was observed. Activation increased the arterial lactate concentration, and during this condition, the lactate flux from the brain was reversed into a slight lactate uptake. Propranolol administration did not change the behavior of the animals during activation. After administration of propranolol, baseline values were unaffected, but beta-adrenergic blockade totally abolished the activation-induced uncoupling of (a-v)(O2) from (a-v)(glc), because both remained constant with an unchanged OGI. The unchanged (a-v)(O2) indicates that CBF remained unchanged compared with CMRO(2).
  
  
  CONCLUSIONS
  beta-Adrenergic blockade by propranolol abolishes the activation-induced uncoupling of cerebral oxygen to glucose metabolism and the changes in (a-v)(O2). This may be of most significance to studies of cerebral activation by the blood oxygen level-dependent fMRI method.
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ina K
authors.initials: IK
authors.lastname: Schmalbruch
authors.forename: Rasmus
authors.initials: R
authors.lastname: Linde
authors.forename: Olaf B
authors.initials: OB
authors.lastname: Paulson
authors.forename: Peter L
authors.initials: PL
authors.lastname: Madsen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D019344:Lactic Acid; D011433:Propranolol