Effects of acetazolamide on cerebrocortical NADH and blood volume.
Acetazolamide (AZ), a potent carbonic anhydrase inhibitor in human and animal tissues, increases cerebral blood flow (CBF) by acidifying cerebral extracellular fluids. To demonstrate the relationship of increased CBF to brain O2 availability after AZ administration, a compensated fluorometer was used to study changes in the cerebrocortical redox balance in rabbits. Seven rabbits were anesthetized with pentobarbital sodium. Excitation light (366 nm) was conducted to the cerebrocortical surface of each animal by a 4-mm-diam fiberoptic light guide. Fluorescence emissions from cerebrocortical NADH (450 nm) were compared at different inspired O2 (FIO2) tensions. Reflected light (366 nm), which was used to determine a correction to the fluorescence signal, was separately quantitated and interpreted as an index of cerebrocortical blood volume. Reductions in FIO2 from 1.0 to 0.21, 0.14, 0.10, and 0.07 resulted in increases in both tissue blood volume and [NADH]. Intravenous AZ (25 mg/kg) increased cerebrocortical blood volume and reduced the [NADH], even during ventilation with 100% O2. The changes in brain redox balance caused by vasodilation with AZ were compared with those caused by vasodilatation with CO2. The NAD+/NADH redox state was a continuous function of FIO2 at all levels of arterial PCO2 (PaCO2), both before and after AZ administration. The improvement in cerebral O2 delivery caused by AZ-induced vasodilation was comparable to that caused by the vasodilatation that results from a PaCO2 elevation approximately equal to 12-15 Torr above normal. The slope of the relationship between [NADH] and FIO2 was similar at normal, low, and high levels of PaCO2. We conclude that AZ administration and PaCO2 elevation improve cerebral oxygenation by similar mechanisms.
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001810:Blood Volume / Q000187:drug effects*; D002245:Carbon Dioxide / Q000032:analysis; D002255:Carbonic Acid / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005470:Fluorometry; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D011817:Rabbits
D009243:NAD; D002245:Carbon Dioxide; D002255:Carbonic Acid; D000086:Acetazolamide; D010100:Oxygen