Hansen M B, Olsen N V, Hyldegaard O
Laboratory for Hyperbaric Medicine, Department of Anesthesia, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Denmark;
J Appl Physiol (1985). 2013 Nov 1;115(9):1254-61. doi: 10.1152/japplphysiol.00516.2013. Epub 2013 Aug 22.
Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.
高压氧疗法（HBOT）或静脉注射羟钴胺（OHCob）均可消除氰化物（CN）诱导的脑间质乳酸和葡萄糖浓度的激增。已证明HBOT可导致全血CN浓度延迟升高，而OHCob可能作为血管内CN清除剂。此外，HBOT可预防CN中毒期间的呼吸窘迫并恢复血压，而OHCob给药则未观察到这种效果。在本报告中，我们通过急性CN中毒期间的微透析评估了HBOT和OHCob对大鼠脑间质乳酸、葡萄糖和甘油浓度以及乳酸与丙酮酸比值的联合作用。将麻醉的大鼠分为三组：1）载体组（动脉内注射1.2 ml等渗NaCl）；2）氰化钾组（动脉内注射5.4 mg/kg）；3）氰化钾、OHCob组（动脉内注射100 mg/kg）及随后的HBOT组（90分钟内284 kPa）。与未治疗的中毒大鼠相比，OHCob和HBOT显著减轻了脑间质乳酸、葡萄糖和甘油浓度的急性激增。此外，与CN中毒对照组相比，联合治疗导致乳酸、葡萄糖和甘油浓度持续较低，以及乳酸与丙酮酸比值较低。在接受OHCob和HBOT的大鼠中，呼吸改善，发绀消失，随后平均动脉血压稳定。目前的研究结果表明，OHCob和HBOT联合给药对CN中毒期间的脑代谢具有有益且持久的影响。
