Naimark A, Cherniack R M
Can Med Assoc J. 1966 Jan 22;94(4):164-70.
Dichlorphenamide was administered to 13 patients with chronic respiratory failure, and the effects on gas exchange at rest and during exercise and on the acid-base state of CSF were observed. The ventilation for a given level of CO(2) production was increased both at rest and during exercise, resulting in an increased arterial Po(2) and decreased Pco(2).The ventilatory stimulation paralleled the development of a metabolic acidosis but was not associated with tissue CO(2) accumulation. Indeed, CSF Pco(2) and the oxygenated mixed venous (rebreathing) Pco(2) fell by the same amount as arterial Pco(2). The level of CO(2) elimination after two minutes of exercise was as great for a given work load after dichlorphenamide as before. These findings do not support the view that the drug impairs CO(2) transport from tissues either at rest or during exercise. They are most consistent with the view that the primary locus of action of dichlorphenamide in therapeutic doses is the kidney. The metabolic acidosis which results is likely the basis of the respiratory stimulatin, perhaps by its effects on the CSF H(2)CO(3)-HCO(3) - system. Inhibition of carbonic anhydrase in the red cell and choroid plexus are probably unimportant effects.
对13例慢性呼吸衰竭患者给予二氯苯磺胺，并观察其对静息及运动时气体交换以及脑脊液酸碱状态的影响。在静息和运动时，对于给定水平的二氧化碳产生量，通气量均增加，导致动脉血氧分压升高，二氧化碳分压降低。通气刺激与代谢性酸中毒的发展平行，但与组织二氧化碳蓄积无关。实际上，脑脊液二氧化碳分压和氧合混合静脉血（再呼吸）二氧化碳分压下降的幅度与动脉二氧化碳分压相同。二氯苯磺胺给药后，运动两分钟后给定工作负荷下的二氧化碳清除水平与给药前相同。这些发现不支持该药物在静息或运动时损害组织二氧化碳转运的观点。它们最符合治疗剂量下二氯苯磺胺的主要作用部位是肾脏这一观点。由此产生的代谢性酸中毒可能是呼吸刺激的基础，或许是通过其对脑脊液碳酸-碳酸氢根系统的影响。红细胞和脉络丛中碳酸酐酶的抑制作用可能并不重要。
