Swenson E R, Grønlund J, Ohlsson J, Hlastala M P
Department of Medicine, University of Washington, Seattle 98195.
J Appl Physiol (1985). 1993 Feb;74(2):838-48. doi: 10.1152/jappl.1993.74.2.838.
The contributions to pulmonary gas exchange of red blood cell (RBC) membrane band 3 protein HCO3(-)-Cl- exchange and carbonic anhydrase- (CA) catalyzed HCO3- dehydration have never been determined directly in the whole animal. We utilized an experimental and model approach to measure these by analysis of phase III exhaled CO2 and O2 profiles in anesthetized dogs. In this method, we inhibit RBC membrane band 3 protein and cytoplasmic CA in RBCs passing the pulmonary capillaries and lung vascular luminal membrane-bound CA during a single ventilatory cycle. This is achieved with appropriately timed right atrial infusions of 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS) to inhibit band 3 protein, ethoxzolamide (a lipophilic CA inhibitor with rapid membrane penetrance) to inhibit RBC and lung tissue CA, and benzolamide (an extremely hydrophilic CA inhibitor with virtually no penetrance into RBC cytoplasm) to inhibit only lung vascular luminal membrane CA. DNDS caused a 15% reduction in CO2 production (VCO2) without any change in O2 consumption (VO2). The addition of benzolamide to DNDS did not cause any further decrease in VCO2. Inhibition of RBC CA by ethoxzolamide caused a 67% reduction in VCO2 and a 11.5% reduction in VO2. Inhibition of lung vascular CA by benzolamide alone caused no statistically significant changes in either VCO2 or VO2. These results are in general agreement with in vitro data and model calculations. The only exceptions are the higher than predicted effect of RBC CA inhibition on VO2 (Bohr effect) and the lack of any contribution to CO2 transfer in the dog by lung vascular CA with access to plasma as a possible consequence of an endogenous plasma CA inhibitor.
红细胞（RBC）膜带3蛋白的HCO3(-)-Cl-交换以及碳酸酐酶（CA）催化的HCO3-脱水对肺气体交换的贡献从未在完整动物中直接测定过。我们采用实验和模型方法，通过分析麻醉犬第三相呼出的CO2和O2曲线来进行测量。在该方法中，我们在单个通气周期内抑制通过肺毛细血管的红细胞中的RBC膜带3蛋白和细胞质CA，以及肺血管腔膜结合的CA。这通过适时地经右心房输注4,4'-二硝基芪-2,2'-二磺酸盐（DNDS）以抑制带3蛋白、乙氧唑胺（一种具有快速膜穿透性的亲脂性CA抑制剂）以抑制RBC和肺组织CA，以及苯甲酰胺（一种几乎不穿透RBC细胞质的极亲水性CA抑制剂）以仅抑制肺血管腔膜CA来实现。DNDS使CO2产生量（VCO2）降低了15%，而O2消耗量（VO2）没有任何变化。在DNDS中添加苯甲酰胺并未导致VCO2进一步降低。乙氧唑胺抑制RBC CA导致VCO2降低了67%，VO2降低了11.5%。单独使用苯甲酰胺抑制肺血管CA对VCO2或VO2均未产生统计学上的显著变化。这些结果与体外数据和模型计算总体一致。唯一的例外是RBC CA抑制对VO2的影响高于预期（波尔效应），以及肺血管CA对犬的CO2转运没有任何贡献，这可能是由于内源性血浆CA抑制剂导致血浆可及性降低的结果。
