Clinical Pharmacology and Toxicology Unit, Carmel Medical Center , Haifa , Israel.
Clin Toxicol (Phila). 2015 Jan;53(1):22-7. doi: 10.3109/15563650.2014.990564. Epub 2014 Dec 17.
More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the survival of cyanide-poisoned mice.
To evaluate the effectiveness of isosorbide dinitrate compared with that of sodium nitrite in cyanide poisoning.
A comparative animal study was performed using 18 rabbits, randomized into 3 study groups. Animals were poisoned intravenously with potassium cyanide (1 mg/kg). The first group was not given any further treatment. The second and third groups were treated intravenously 1 min after poisoning with sodium nitrite (6 mg/kg) and isosorbide dinitrate (50 μg/kg), respectively. The primary outcome was short-term survival of up to 30 min. Secondary outcomes included time to death, a clinical score, mean blood pressure, pulse, blood pH, and lactate and methemoglobin levels.
Rabbits treated with isosorbide dinitrate or sodium nitrite survived while only one untreated rabbit survived. Median time to death of the 5 poisoned and untreated animals was 10 min. All the animals collapsed soon after poisoning, exhibiting rapidly disturbed vital signs and developed lactic metabolic acidosis; average peak blood lactate levels were 15.5-19.1 mmol/L at 10 min after poisoning. The treated animals improved gradually with practically full recovery of the clinical scores, vital signs, and blood gas levels. Sodium nitrite administration raised methemoglobin to an average peak of 7.9%, while isosorbide dinitrate did not change methemoglobin levels.
Early administration of isosorbide dinitrate improved the short-term survival of cyanide-poisoned rabbits. Isosorbide dinitrate shows potential as an antidote for cyanide poisoning and may exert its effect using a nitric-oxide-dependent mechanism.
需要更有效、快速给药、更安全的解毒剂来治疗氰化物中毒。先前的研究已经证明硝酸异山梨酯对氰化物中毒小鼠的生存有益。
评估硝酸异山梨酯与亚硝酸钠在氰化物中毒中的疗效。
使用 18 只兔子进行了一项比较性动物研究，随机分为 3 个研究组。动物通过静脉注射氰化钾（1mg/kg）中毒。第一组未给予任何进一步的治疗。第二组和第三组在中毒后 1 分钟内分别静脉注射亚硝酸钠（6mg/kg）和硝酸异山梨酯（50μg/kg）。主要结果是 30 分钟内的短期存活。次要结果包括死亡时间、临床评分、平均血压、脉搏、血 pH 值以及乳酸和高铁血红蛋白水平。
接受硝酸异山梨酯或亚硝酸钠治疗的兔子存活，而未接受治疗的兔子中只有 1 只存活。5 只中毒且未接受治疗的动物的中位死亡时间为 10 分钟。所有动物中毒后很快就倒下，生命体征迅速紊乱，并发生乳酸代谢性酸中毒；中毒后 10 分钟平均血乳酸峰值为 15.5-19.1mmol/L。治疗动物逐渐好转，临床评分、生命体征和血气水平几乎完全恢复。亚硝酸钠给药使高铁血红蛋白平均峰值达到 7.9%，而硝酸异山梨酯没有改变高铁血红蛋白水平。
早期给予硝酸异山梨酯可提高氰化物中毒兔子的短期生存率。硝酸异山梨酯作为氰化物中毒的解毒剂具有潜力，可能通过一氧化氮依赖的机制发挥作用。
