This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmalbruch, I. K. Articles by Madsen, P. L. Search for Related Content PubMed PubMed Citation Articles by Schmalbruch, I. K. Articles by Madsen, P. L. Related Collections Animal models of human disease Energy metabolism Other Research

(Stroke. 2002;33:251.)
© 2002 American Heart Association, Inc.

Original Contributions

Activation-Induced Resetting of Cerebral Metabolism and Flow Is Abolished by ß-Adrenergic Blockade With Propranolol

Ina K. Schmalbruch, MD, PhD; Rasmus Linde, PhD; Olaf B. Paulson, MD, DMSc Peter L. Madsen, MD, DMSc

From the Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Correspondence to O.B. Paulson, Neurobiology Research Unit N9201, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen Ø, Denmark. E-mail paulson{at}nru.dk

Background and Purpose— 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 (CMRO₂). Our purpose was to investigate the influence of ß-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 CMRO₂ and CMR_glc, the oxygen-glucose index (OGI), was calculated.

Results— Without ß-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/CMRO₂ 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 ß-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 CMRO₂.

Conclusions— ß-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.

Key Words: cerebral blood flow • cerebral cortex • cerebral metabolism • glucose • lactates • oxygen • propranolol

This article has been cited by other articles:

				T. S. Seifert, P. Brassard, T. B. Jorgensen, A. J. Hamada, P. Rasmussen, B. Quistorff, N. H. Secher, and H. B. Nielsen Cerebral non-oxidative carbohydrate consumption in humans driven by adrenaline J. Physiol., January 1, 2009; 587(1): 285 - 293. [Abstract] [Full Text] [PDF]

				T. S. Larsen, P. Rasmussen, M. Overgaard, N. H. Secher, and H. B. Nielsen Non-selective {beta}-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans J. Physiol., June 1, 2008; 586(11): 2807 - 2815. [Abstract] [Full Text] [PDF]

				N. H. Secher, T. Seifert, and J. J. Van Lieshout Cerebral blood flow and metabolism during exercise: implications for fatigue J Appl Physiol, January 1, 2008; 104(1): 306 - 314. [Abstract] [Full Text] [PDF]

				M. K. Dalsgaard, S. Ogoh, E. A. Dawson, C. C. Yoshiga, B. Quistorff, and N. H. Secher Cerebral carbohydrate cost of physical exertion in humans Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2004; 287(3): R534 - R540. [Abstract] [Full Text] [PDF]

				M. K. Dalsgaard, P. Ott, F. Dela, A. Juul, B. K. Pedersen, J. Warberg, J. Fahrenkrug, and N. H. Secher The CSF and arterial to internal jugular venous hormonal differences during exercise in humans Exp Physiol, May 1, 2004; 89(3): 271 - 277. [Abstract] [Full Text] [PDF]

				M. K. Dalsgaard, B. Quistorff, E. R. Danielsen, C. Selmer, T. Vogelsang, and N. H. Secher A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain J. Physiol., January 15, 2004; 554(2): 571 - 578. [Abstract] [Full Text] [PDF]