Lawson-Smith P, Jansen E C, Hilsted L, Johnsen A H, Hyldegaard O
Laboratory of Hyperbaric Medicine, Department of Anesthesia, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Denmark.
Undersea Hyperb Med. 2011 Jan-Feb;38(1):17-26.
Cyanide and carbon monoxide, which are often found in fire victims, are toxic gases emitted from fires. Cyanide and carbon monoxide have similar molecular structure. Cyanide binds to the enzyme cytochrome oxidase a, a3 similar to carbon monoxide, thus blocking the mitochondrial respiration chain causing depletion of adenosine triphosphate. Hyperbaric oxygen (HBO2) is recommended for treating carbon monoxide poisoning. The therapeutic effect is due to a high oxygen pressure removing carbon monoxide from the cells. We hypothesise that HBO2 induces changes in whole-blood-cyanide by a competitive mechanism forcing cyanide out of cellular tissues. A rat model was developed to study this effect. Female Sprague Dawley rats were anesthetized with a fentanyl + fluanizone combination and midazolam given subcutaneously (s.c.). Rats were poisoned with 5.4 mg/kg KCN injected intra-peritoneally in Group 1 and intra-arterially in Group 2. Blood samples were taken immediately after poisoning, and at one and a half, three and five hours. Blood was drawn from a jugular vein in Group 1 and from a femoral artery in Group 2. Group 1 rats were divided into a control group of 12 rats without HBO2, 10 rats had acute HBO2 immediately after poisoning and a group of 10 rats had HBO2 one and a half hours after poisoning. Group 2 rats were divided into a control group and an acute HBO2 group, with 10 rats in both groups. Whole-blood-cyanide concentrations were measured using the Conway method based on diffusion and the subsequent formation of cyanocobalamin measured by a spectrophotometer. Results showed that whole-blood-cyanide concentration in Group 1 controls and acute HBO2 initially rose and then fell towards zero. In rats treated with delayed HBO2, the reduction in whole-blood-cyanide concentration was significantly less as compared to controls and acute HBO2-treated rats. Group 2 controls whole-blood-cyanide concentration decreased towards zero throughout the observation period. However, in Group 2 acute HBO2-treated rats a secondary rise in whole-blood-cyanide was observed. The study indicates that HBO2 can move cyanide from tissue to blood. These findings may be of clinical importance, as combined HBO2 and antidote treatment, may accelerate detoxification.
氰化物和一氧化碳常见于火灾受害者体内，是火灾释放出的有毒气体。氰化物和一氧化碳具有相似的分子结构。氰化物与细胞色素氧化酶a、a3结合，类似于一氧化碳，从而阻断线粒体呼吸链，导致三磷酸腺苷耗竭。高压氧（HBO2）被推荐用于治疗一氧化碳中毒。其治疗效果是由于高氧分压将一氧化碳从细胞中去除。我们假设HBO2通过竞争机制促使氰化物从细胞组织中排出，从而引起全血氰化物的变化。为此建立了一个大鼠模型来研究这种效应。雌性斯普拉格-道利大鼠用芬太尼+氟胺酮组合和咪达唑仑皮下注射麻醉。第1组大鼠腹腔注射5.4mg/kg氰化钾中毒，第2组大鼠动脉内注射中毒。中毒后立即、1.5小时、3小时和5小时采集血样。第1组从颈静脉取血，第2组从股动脉取血。第1组大鼠分为12只未接受HBO2的对照组、10只中毒后立即接受急性HBO2治疗的大鼠组和10只中毒后1.5小时接受HBO2治疗的大鼠组。第2组大鼠分为对照组和急性HBO2组，每组10只。采用基于扩散的康威法测量全血氰化物浓度，随后用分光光度计测量氰钴胺的形成量。结果显示，第1组对照组和急性HBO2组的全血氰化物浓度最初升高，然后降至零。在接受延迟HBO2治疗的大鼠中，与对照组和急性HBO2治疗的大鼠相比，全血氰化物浓度的降低明显较少。第2组对照组的全血氰化物浓度在整个观察期内降至零。然而，在第2组接受急性HBO2治疗的大鼠中，观察到全血氰化物出现二次升高。该研究表明，HBO2可使氰化物从组织转移至血液。这些发现可能具有临床重要性，因为联合HBO2和解毒剂治疗可能会加速解毒。
