Acetazolamide-induced increase in blood flow to rabbit organs is confirmed using colored microspheres.
Inhibitors of carbonic anhydrase activity have been found to increase blood and organ PCO2 and to increase blood flow (BF) in individual organs. To determine whether carbonic anhydrase inhibition coordinately induces an increase in BF in several organs, we assayed the effect of the carbonic anhydrase inhibitor, acetazolamide (AZ), on BF in rabbit organs using the colored microsphere (CM) assay. Eight female white rabbits were anesthetized with ketamine and urethane, and administered three sequential doses of 4 mg/kg AZ. After each dose, the rabbits were injected with 9 x 10(5) CMs of different colors, and arterial blood was collected. We found that AZ had no effect on blood pressure, body temperature, hemoglobin concentration, or PaCO2. In contrast, 12 mg/kg AZ significantly increased PaO2 and significantly decreased base excess. When we measured organ BF, we observed, in response to 12 mg/kg AZ, an 82% increase in brain BF and a 55% increase in kidney BF, but no change in BF of the liver, stomach wall, or abdominal muscle. These findings suggest that the inhibition of carbonic anhydrase activity by AZ, which decreases the rate of CO2 conversion to HCO3-, causes the retention of CO2 in tissues and organs, and thus increases BF in specific organs. Administration of carbonic anhydrase inhibitors, such as AZ, may increase BF to the brain and kidney without reducing PaO2, thereby increasing the supply of oxygen in conditions involving hypoxia such as ischemia and shock.
Taki
K
K
Department of Emergency Medicine, Saga Medical College, Japan.
Hirahara
K
K
Tomita
S
S
Totoki
T
T
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000098:blood supply*; D008099:Liver / Q000098:blood supply*; D008863:Microspheres; D018482:Muscle, Skeletal / Q000098:blood supply*; D009929:Organ Size; D011817:Rabbits; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects