Alston Theodore A
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
J Anesth Hist. 2016 Jul;2(3):85-8. doi: 10.1016/j.janh.2016.04.008. Epub 2016 Apr 22.
Inhaled chloroform anesthesia was introduced in 1847. Soon thereafter, the chemical reactivity of aerobically heated chloroform permitted John Snow and Claude Bernard to do seminal experiments in the assay of drug levels and drug metabolism. However, it was not widely appreciated until a clinical mishap in 1899 that thermal decomposition generated significant levels of toxic phosgene from air-polluting quantities of chloroform in poorly ventilated operating rooms that were illuminated by flames. Phosgene is also generated metabolically from chloroform. A clue appeared in the 1950s when subanesthetic traces of inhaled chloroform proved accidentally lethal to strains of male mice spontaneously expressing high levels of chloroform-metabolizing enzymes. Furthermore, in microbial experiments of 1967, the reactive chloroform molecule was inadvertently discovered to selectively inactivate vitamin B12-dependent enzymes. Chloroform can also activate enzymes. As a solvent, it was serendipitously found in 1903 to activate what is now known as plasminogen to plasmin.
1847年引入了吸入氯仿麻醉法。此后不久，有氧加热氯仿的化学反应活性使约翰·斯诺和克劳德·伯纳德能够在药物水平测定和药物代谢方面开展开创性实验。然而，直到1899年发生一起临床事故，人们才广泛认识到，在通风不良且由火焰照明的手术室中，热分解会从污染空气的氯仿量中产生大量有毒光气。光气也可由氯仿代谢产生。20世纪50年代出现了一条线索，当时发现亚麻醉剂量的吸入氯仿对自发表达高水平氯仿代谢酶的雄性小鼠品系具有意外致死性。此外，在1967年的微生物实验中，意外发现具有反应活性的氯仿分子能选择性地使维生素B12依赖性酶失活。氯仿还能激活酶。作为一种溶剂，1903年意外发现它能将现在所知的纤溶酶原激活为纤溶酶。
