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The Effect of Acetazolamide on Cerebral Blood Flow and Oxygen Utilization in the Rhesus Monkey
Authors:B. E. Laux and M. E. Raichle
Affiliation:Division of Radiation Sciences, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110;Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110
Abstract:The brain is critically dependent for its moment to moment function and survival on an adequate supply of oxygen. The enzyme carbonic anhydrase (EC 4.2.1.1) may play an important role in oxygen delivery to brain tissue by facilitating the hydration of metabolically produced carbon dioxide in erythrocytes in brain capillaries, thus permitting the Bohr effect to occur. We examined the effect of 30 mg/kg i.v. acetazolamide, a potent inhibitor of carbonic anhydrase, upon cerebral blood flow and oxygen consumption in lightly anesthetized, passively ventilated rhesus monkeys. Cerebral blood flow and oxygen consumption were measured with oxygen-15-labeled water and oxygen-15-labeled oxyhemoglobin, respectively, injected into the internal carotid artery and monitored externally. Acetazolamide produced an immediate and significant increase in cerebral blood flow (from a mean of 64.7 to 83.8 ml/100 g per min), an increase in arterial carbon dioxide tension (from a mean of 40.7 to 47.5 torr), and a decrease in cerebral oxygen consumption (from a mean of 4.16 to 2.82 ml/100 g per min). Because the change in cerebral oxygen consumption occurred within minutes of the administration of acetazolamide, we believe that this effect probably was not due to a direct action on brain cells but was achieved by an interference with oxygen unloading in brain capillaries. A resultant tissue hypoxia might well explain part of the observed increase in cerebral blood flow.
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