Pharmacodynamics of ferrihemoglobin formation by 4-DMAP under hypoxic condition / 解放军医学杂志

ABSTRACT

Objective To guide the therapy for cyanide poisoning patients on plateau, the effect of hypoxia on the efficiency of 4-(N, N-dimethyl)-aminophenol (4-DMAP) in ferrihemoglobin (MHb) formation was investigated. Methods Rabbits were raised in hypoxic condition (4500m altitude) as acute-hypoxic animal model, and MHb concentration was determined by spectrophotography at the length of 635nm after 4-DMAP injection. Results There was no difference in hemoglobin content and MHb concentration between acute acutehypoxia group and controls. But in hypoxic rabbits, MHb formation as induced by 4-DMAP was improved distinctly. 30%-40% MHb concentration formation (optimal anti-cyanide concentration) was induced by 20mg/kg 4-DMAP in hypoxic rabbits, compared to 25-30mg/kg in control rabbits. However, when hypoxic rabbits received 25-30mg/kg 4-DMAP, which was the optimal dose for treatment of cyanide poisoning in normoxic animals, the animals manifested even worse symptoms of hypoxia, eren death occurred. Moreover, the level of MHb in acute-hypoxic models maintained longer than that in controls. The effect of 4-DMAP in MHb formation was closely related with duration of hypoxia. During hypoxia period from 1d to 5d, MHb concentration was increased gradually along with the duration of hypoxia, peaking on the 5d, and it started to decline on 7d, but it was still higher than that in control group. Conclusion Hypoxia enhances the effect of 4-DMAP in MHb formation and lowers the metabolism of MHb.