RESUMO
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.
RESUMO
Under anesthesia and artificial respiration, all the dogs were injected with HCN 8 mg/kg intravenously. 2 minutes after HCN injection, 4-dimethylaminophenol( DM -AP) 3.2mg/kg,sodium nitrite(NaNO2)20 mg/kg,or dicobalt edetate(Co2EDTA) 15 mg/kg was given intravenously to different animals respectively. The changes of hemodynamics of the dogs were observed before and after the administration of the 3 HCN antidotes.It was found that intravenous injection of HCN rapidly induced a progressive decrease of heart rate(HR),stroke index(SI), cardiac index (CI),mean aortic pressure (MAP),left ventricular pressure(LVP) and ?dp/dtmax and a persistent increase of total peripheral vascular resistance (TPVR) and mean pulmonary arterial pressure (MPAP). If not treated,the dogs would died subsquently 4-9.5 minutes after HCN injection because of cardiac failure.2 to 8 minutes after DMAP administration, CI, MAP, LVP and?dp/dtmax increased markedly,and TPVR and MPAP would recover a little later. 4-6minutes after NaNO2 administration, ?dp/dtmax increased markedly, and CI, MAP, LVP, TPVR and MPAP returned to the normal. 6 minutes after Co2EDTA administration, MAP elevated markedly, LVP and?dp/dtmax returued to the normal, and C1, TPVR and MPAP would recover a little later. When observation was made again one hour after treatment, there was a remarkable decrease of blood pressure in NaNO2 and Co2EDTA treated animals and a slight decrease of blood pressure in DMAP treated ones.The conclusions based on the results are as follows:1. The ability of DMAP to restore the circulatory functions after HCN poisoning is more rapid and powerful than that of Co2EDTA or NaNO2.2. The cardiovascular functions restored by DMAP are more stable than those restored by the other two agents.3. DMAP and NaNO2 can rapidly reverse the HCN-iuduced damages on the cardiovascular functions, which may be a part of the anticyanide ability of these 2 drugs.
RESUMO
The effects of 4 efficacious cyanide antidotes, 4-dimethylaminophenol (4-DMAP) , P-aminopropiophenone hydrochloride (PAPP. HC1), NaNO2, and di-cobalt ethyleneamino-tetraacetate (Co2-EDTA), on the liver and kidney functions and on the blood gases and serum levels of lactate and potassium were investigated in rabbits. The former 3 agents can convert hemoglobin into me-themoglobin, and the dosages that are required to convert 30~35% of total hemoglobin into methemoglobjn are 15mg/kg, 35mg/kg, and 55 mg/kg for 4-DMAP, PAPP . HC1 and NaNO2 respectively. Obviously, 4-DMAP is the most potent one. Co2-EDTA can directly combine with cyanides to form nontoxic complex without affecting hemoglobin.According to the results of the 2-hour observation on the acute experiments in rabbits, all the 4 agents exert no harmful effects on the liver functions. 4-DMAP and PAPP. HC1 are also not harmful to the kidneys. But serum urea nitrogen was increased to 204% above the normal 30 minutes after intravenous NaNO2 (110 mg/kg) , and to 171% 90 minutes after intravenous Co2-EDTA(40 mg/kg) . Apparently, both the agents are injurious to the renal functions.4-DMAP can decrease the blood level of lactate. NaNO2 exerts most marked effect on the serum level of potassium. After the administration of 55 mg/kg and 110 mg/kg of NaNO2/the serum potassium level was increased 2.5 and 4.5 fold respectively. The larger the dose of NaNO2, the higher the serum potassium level, and more quickly the elevation of potassium level occurs.4-DMAP has a transient action on the arterial Po2 which usually returns to normal in 30 minutes. The action of NaNO2 and PAPP. HC1 on the blood gases are essentially similar, they can quickly lower the arterial Po2 but its recovery to normal is sluggish.
RESUMO
The effects of 4-DMAP and NaNO2 on the hemodynamics of dogs suffering from acute hemorrhage complicated with cyanide poisoning were studied. It was found that the administration of 4-DMAP could brought about an increase of the cardiovascular functions in the experimental animals. Although the increase was temporal and not very impressive, it played an important role to prevent the dogs from developing cardiovascular collapse during the period of observation. On the other hand, the administration of NaNO2 resulted in a transient excitation for 1-2 minutes and then a prolonged and progressive depression of the cardiovascular functions, and all the experimental animals died from cardiovascular failure within 13-19 minutes after NaNO2 injection.The results of this study indicate that 4-DMAP as a therapeutic agent for acute hemorrhage complicated with cyanide poisoning is superior to NaNO2 since the former can produce an excitation of the cardiovascular functions while the latter a progressive depression and eventually a failure of the cardiovascular functions.