Acetazolamide slows VA/Q matching after changes in regional blood flow.
Inhibition of carbonic anhydrase (CA) by acetazolamide increases ventilation-perfusion (VA/Q) heterogeneity (E. R. Swenson, H. T. Robertson, and M. P. Hlastala. J. Clin. Invest. 92: 702-709, 1993), possibly because of slowing of CO2/H(+)-dependent mechanisms of VA/Q matching with temporal fluctuations of regional ventilation and perfusion. To study this concept, we imposed abrupt changes in regional perfusion by lobar or left main pulmonary artery occlusions (PAOs) in anesthetized mechanically ventilated dogs before and after CA inhibition (20 mg/kg iv acetazolamide). The rate of ventilation redistribution and change in VA/Q distributions with changes in perfusion were measured by planar gamma imaging of the lungs during continuous inhalation of 81mKr gas ventilation scanning and the multiple inert-gas elimination technique. PAO for 5 min caused regional Kr activity to fall by 30 +/- 5% (SD) with a half time (t1/2) of 75 +/- 10 s. With release of the occlusion, counts returned to baseline with t1/2 of 79 +/- 12 s. Acetazolamide increased these respective t1/2 values (161 +/- 16 and 180 +/- 17 s). Consistent with these kinetics, VA/Q mismatch was greater with lobar PAO at 2 min but not at 10 min with CA inhibition compared with that caused by lobar PAO alone. Cyclical lobar PAO and release (10 cycles of 1-min occlusion and 1-min release) caused more VA/Q heterogeneity during CA inhibition. The arterial-to-alveolar inert-gas area difference rose minimally from 0.18 to 0.23 (P < 0.05) with cyclical PAO and from 0.24 to 0.48 (P < 0.01) after CA inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Swenson
E R
ER
Medical Service, Veteran Affairs Medical Center, Seattle, Washington 98108, USA.
Graham
M M
MM
Hlastala
M P
MP
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D002256:Carbonic Anhydrases / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D012119:Respiration / Q000187:drug effects* / Q000502:physiology; D012129:Respiratory Function Tests; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects* / Q000502:physiology
D002256:Carbonic Anhydrases; D000086:Acetazolamide