Klimmek R, Krettek C, Werner H W
Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Federal Republic of Germany.
Arch Toxicol. 1988;62(2-3):152-60. doi: 10.1007/BF00570133.
The ferrihaemoglobin (HbFe3+) formation by amyl nitrite (AN) or sodium nitrite (NaNO2) was studied in different species including man, in vivo and in vitro. In in vivo studies AN was administered intravenously (i.v.), intramuscularly (i.m.), by inhalation, or orally. NaNO2 was injected i.v.. AN i.v. produced HbFe3+ much more rapidly than NaNO2 in dogs, cats, rabbits, and rats. In dogs, i.m. injection of AN was followed by a very slow linear increase in the HbFe3+ content. Inhalation of AN did not lead to HbFe3+ formation in dogs unless it was rebreathed in a closed (bag) or not completely open (gas mask) system. HbFe3+ was produced by oral AN in dogs, the effect being enhanced by addition of DMSO. Inhalation of AN by human volunteers in a gas mask and from ampoules crushed close to the nose did not induce haemoglobin oxidation to a practically significant extent, but it was associated with headache, tiredness, dizziness, and a fall in blood pressure. In in vitro studies, in contrast to NaNO2, AN produced HbFe3+ instantaneously in erythrocytes of various species and in purified human haemoglobin. AN 1 mol yielded 2 mol Fe3+. Only 20% of the oxygen released during the oxidation of haemoglobin by AN or NaNO2 was recovered. In 0.2 M phosphate buffer, pH 7.4, 0.01 mol O2/mol AN was consumed. CO2 was released in the presence of AN, but not of NaNO2, from blood, plasma, and 0.02 M NaHCO3 solution. The ratio (lactate)/(pyruvate) decreased when HbFe3+ was formed by AN or NaNO2.
在包括人类在内的不同物种中，对亚硝酸戊酯（AN）或亚硝酸钠（NaNO₂）诱导高铁血红蛋白（HbFe³⁺）形成进行了体内和体外研究。在体内研究中，AN通过静脉内（i.v.）、肌肉内（i.m.）、吸入或口服给药。NaNO₂通过静脉注射给药。在狗、猫、兔子和大鼠中，静脉注射AN比注射NaNO₂能更快地产生HbFe³⁺。在狗中，肌肉注射AN后，HbFe³⁺含量呈非常缓慢的线性增加。除非在封闭（袋子）或未完全打开（防毒面具）系统中进行再呼吸，否则狗吸入AN不会导致HbFe³⁺形成。狗口服AN可产生HbFe³⁺，加入二甲基亚砜（DMSO）可增强其效果。人类志愿者在防毒面具中并在靠近鼻子处碾碎安瓿吸入AN，并未在实际显著程度上诱导血红蛋白氧化，但会伴有头痛、疲劳、头晕和血压下降。在体外研究中，与NaNO₂不同，AN能在各种物种的红细胞和纯化的人血红蛋白中瞬间产生HbFe³⁺。1摩尔AN产生2摩尔Fe³⁺。在AN或NaNO₂氧化血红蛋白过程中释放的氧气仅回收了20%。在pH 7.4的0.2 M磷酸盐缓冲液中，每摩尔AN消耗0.01摩尔O₂。在有AN存在时，血液、血浆和0.02 M NaHCO₃溶液会释放CO₂，而有NaNO₂时则不会。当AN或NaNO₂形成HbFe³⁺时，（乳酸）/（丙酮酸）比值降低。
