Pluta Ryszard M
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Acta Neurochir Suppl. 2013;115:49-51. doi: 10.1007/978-3-7091-1192-5_11.
In preclinical studies, infusion of sodium nitrite delivers nitric oxide (NO) as treatment of vasospasm after subarachnoid hemorrhage. We evaluated safety and toxicity of intravenous nitrite administration in healthy volunteers infused with increasing doses of sodium nitrite for 48 h. Twelve volunteers (5 men, 7 women; mean age was 38.8 years, range 27-56 years) participated in the study. The starting sodium nitrite dose was 4.2 mg/kg/h, and it was doubled for each subsequent volunteer up to a maximal dose of 533.8 mg/kg/h at which a clinically silent dose-limiting toxicity (DLT) was observed. Toxicity included a transient decrease of mean arterial blood pressure or asymptomatic increase of methemoglobin level above 5%. The maximal tolerated dose (MTD) was 267 mg/kg/h. S-Nitrosothiols increased significantly in plasma, confirming in vivo sodium nitrite reduction to NO and encouraging its use against vasospasm and ischemia-reperfusion injury to the brain, kidneys, liver, and heart.
在临床前研究中，输注亚硝酸钠可释放一氧化氮（NO），用于治疗蛛网膜下腔出血后的血管痉挛。我们评估了在健康志愿者中静脉输注亚硝酸钠48小时的安全性和毒性，输注剂量逐渐增加。12名志愿者（5名男性，7名女性；平均年龄38.8岁，范围27 - 56岁）参与了该研究。亚硝酸钠起始剂量为4.2毫克/千克/小时，随后每位志愿者的剂量翻倍，直至最大剂量533.8毫克/千克/小时，此时观察到了临床上无症状的剂量限制性毒性（DLT）。毒性包括平均动脉血压短暂下降或高铁血红蛋白水平无症状升高超过5%。最大耐受剂量（MTD）为267毫克/千克/小时。血浆中的S - 亚硝基硫醇显著增加，证实了亚硝酸钠在体内还原为NO，并鼓励将其用于对抗血管痉挛以及脑、肾、肝和心脏的缺血 - 再灌注损伤。
