Stennett Amanda K, Murray Robert J, Roy James W, Gainer John L
Fresenius Medical Care, Lexington, Massachusetts, USA.
Shock. 2007 Sep;28(3):339-44. doi: 10.1097/shk.0b013e3180487b2d.
Trans-sodium crocetinate (TSC) has been found to alleviate the symptoms of hemorrhagic shock in that, after the drug is given to hemorrhaged rats, blood pressure rises, elevated lactate levels are reduced, cellular damage in the liver and kidney is less, and survival is increased. The mechanism of action proposed for TSC is that it increases the diffusion of oxygen through blood plasma and into the tissue. The study reported here explores another proposed mechanism, the scavenging of free radicals. It is shown that TSC does scavenge radicals and may be more efficient than other free-radical scavengers. However, this may not be the mechanism of action for TSC during hemorrhagic shock. Not only are the TSC concentrations needed for radical scavenging greater than those which provide beneficial effects in hemorrhagic shock, but it is also shown that another radical scavenger, trolox, has no effect on oxygen consumption during shock. Trans-sodium crocetinate clearly holds promise as a useful treatment of hemorrhagic shock. Pharmacokinetics data are presented for different modes of administration. Initial studies suggest that instillation of TSC into the trachea or intramuscular injection may provide useful alternative treatment routes.
反式金盏花素钠(TSC)已被发现可缓解失血性休克的症状,即给出血性休克大鼠注射该药物后,血压上升,升高的乳酸水平降低,肝肾细胞损伤减轻,存活率提高。针对TSC提出的作用机制是,它可增加氧气通过血浆扩散到组织中的能力。本文报道的研究探索了另一种提出的机制,即清除自由基。结果表明,TSC确实能清除自由基,且可能比其他自由基清除剂更有效。然而,这可能不是TSC在失血性休克期间的作用机制。不仅清除自由基所需的TSC浓度高于在失血性休克中产生有益效果的浓度,而且还表明另一种自由基清除剂生育三烯酚在休克期间对氧消耗没有影响。反式金盏花素钠显然有望成为治疗失血性休克的有效药物。文中给出了不同给药方式的药代动力学数据。初步研究表明,将TSC滴入气管或肌肉注射可能提供有用的替代治疗途径。