White P, Coburn R F, Williams W J, Goldwein M I, Rother M L, Shafer B C
J Clin Invest. 1967 Dec;46(12):1986-98. doi: 10.1172/JCI105688.
The rate of endogenous carbon monoxide production ( Vco), determined by the closed rebreathing system technique, was elevated above the normal range in four of five patients studied with ineffective erythropoiesis (four patients with primary refractory anemia, one with thalassemia). The mean molar ratio of Vco to Vheme (rate of circulating heme catabolism, determined from (51)Cr red cell survival curves) was 3.0 +/- 0.6 (SE), indicating that most of the CO originated from sources other than circulating erythrocyte hemoglobin, in contrast to previous findings in patients with hemolytic anemia, where Vco paralleled Vheme closely.After administration of glycine-2-(14)C to these patients, endogenous CO was isolated by washout of body CO stores at high pO(2) or by reacting peripheral venous blood samples with ferricyanide. The CO was then oxidized to CO(2) by palladium chloride and trapped for counting in a liquid scintillation spectrometer. "Early labeled" peaks of (14)CO were demonstrated which paralleled "early labeled" peaks of stercobilin and preceded maximal labeling of circulating heme. Production of "early labeled" (14)CO in patients with ineffective erythropoiesis was greatly increased, up to 14 times that found in a normal subject. The increased Vco and "early (14)CO" production shown by these patients are presumably related mainly to heme catabolism in the marrow. The possibility exists that hepatic heme and porphyrin compounds may also contribute significantly to Vco, as suggested by the finding of a high Vco in an additional patient with porphyria cutanea tarda.
采用密闭式再呼吸系统技术测定的内源性一氧化碳生成率（Vco），在5例红细胞生成无效的患者（4例原发性难治性贫血患者、1例地中海贫血患者）中有4例高于正常范围。Vco与Vheme（循环血红素分解代谢率，根据（51）Cr红细胞存活曲线确定）的平均摩尔比为3.0±0.6（标准误），这表明与溶血性贫血患者以前的发现相反，大多数CO并非源自循环红细胞血红蛋白，在溶血性贫血患者中Vco与Vheme密切平行。给这些患者注射甘氨酸-2-（14）C后，通过在高pO₂时排出体内CO储备或使外周静脉血样本与铁氰化物反应来分离内源性CO。然后CO被氯化钯氧化为CO₂，并捕获以便在液体闪烁光谱仪中计数。显示出“早期标记”的（14）CO峰，其与粪胆素的“早期标记”峰平行且先于循环血红素的最大标记。红细胞生成无效患者中“早期标记”的（14）CO生成量大幅增加，高达正常受试者的14倍。这些患者显示出的Vco增加和“早期（14）CO”生成增加可能主要与骨髓中的血红素分解代谢有关。正如在另外1例迟发性皮肤卟啉症患者中发现高Vco所提示的那样，肝脏血红素和卟啉化合物也可能对Vco有显著贡献。
